Clinical question: Can idarucizumab reverse anticoagulation effects of dabigatran in a timely manner for urgent surgery or in the event of bleeding?

Background: Reversing the anticoagulant properties of anticoagulants can be important in the event of a life-threatening bleed, or if patients taking these medications need urgent surgery or other interventions. Idarucizumab, a humanized monoclonal antibody fragment, can reverse anticoagulant activity of dabigatran, increasing its acceptance for prescribing physicians as well as patients.

Study design: Multicenter prospective single cohort study.

Setting: 173 sites, 39 countries.

Dr. Kamath is a hospitalist and medical director of quality and patient safety, Duke Regional Hospital, Duke University Health System.

Clinical question: Can idarucizumab reverse anticoagulation effects of dabigatran in a timely manner for urgent surgery or in the event of bleeding?

Background: Reversing the anticoagulant properties of anticoagulants can be important in the event of a life-threatening bleed, or if patients taking these medications need urgent surgery or other interventions. Idarucizumab, a humanized monoclonal antibody fragment, can reverse anticoagulant activity of dabigatran, increasing its acceptance for prescribing physicians as well as patients.

Study design: Multicenter prospective single cohort study.

Setting: 173 sites, 39 countries.

Dr. Kamath is a hospitalist and medical director of quality and patient safety, Duke Regional Hospital, Duke University Health System.

Clinical question: Can idarucizumab reverse anticoagulation effects of dabigatran in a timely manner for urgent surgery or in the event of bleeding?

Background: Reversing the anticoagulant properties of anticoagulants can be important in the event of a life-threatening bleed, or if patients taking these medications need urgent surgery or other interventions. Idarucizumab, a humanized monoclonal antibody fragment, can reverse anticoagulant activity of dabigatran, increasing its acceptance for prescribing physicians as well as patients.

Study design: Multicenter prospective single cohort study.

Setting: 173 sites, 39 countries.

Dr. Kamath is a hospitalist and medical director of quality and patient safety, Duke Regional Hospital, Duke University Health System.

SAN DIEGO – High-potency marijuana use appears to be associated with an increased risk of a first psychotic episode, based on a case-control study conducted in Europe.

“Daily users of a strong type of cannabis face a significant increase in the probability of developing a psychotic disorder,” reported Marta Di Forti, MD, PhD, MRC, lead author of a study whose preliminary results were presented at the International Congress on Schizophrenia Research.

Dr. Di Forti spawned a media boomlet in 2015 when she and her colleagues raised the prospect of a possible association between so-called “skunk” marijuana and first psychotic episodes. In their study of subjects in London with first-time psychotic episodes and matched population controls, those who had psychotic episodes were three times (adjusted odds ratio: 2.92; 95% confidence interval, 1.52-3.45; P = .001) as likely as controls to have used “skunk” marijuana (Lancet Psychiatry. 2015 Mar;2[3]:233-8).

In the new study, Dr. Di Forti and her colleagues analyzed 1,200 first-incident cases of psychosis that were captured between the years 2010 and 2013 by the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions project (EU-GEI). The researchers compared the cases to 1,300 population-based controls in five unidentified European countries and found that daily users of high-potency marijuana had the highest adjusted odds ratio (4.5-8, statistical significance not available) of a psychotic episode (Schizophr Bull. 2017 Mar:43:S30. doi: 10.1093/schbul/sbx021.078). “This effect is significant even after controlling for other drugs of abuse such as stimulants, tobacco and alcohol, and main sociodemographic confounders,” the researchers wrote in their abstract.

“The biology of cannabis-associated psychosis is still unclear,” Dr. Di Forti said in an interview. “Nevertheless, we know that THC (tetrahydrocannabinol) binds with two receptors called CB1 and CB2. They’re part of the endocannabinoid system, which from uterus onward protects our central nervous systems from insults. It activates on demand if the brain goes on hypoxia or we experience a brain injury.”

“CB1 activation leads to changes in the transmission of both GABA and glutamate. Downstream, they affect the dopamine system, which is biologically linked to psychosis.”

Dr. Di Forti dismissed the idea that people at risk for psychosis are drawn to high-potency marijuana. “Using genetic data, we’ve showed that cannabis users – both cases and controls – did not have a higher genetic load for schizophrenia than those who never used (marijuana),” she said (Lancet Psychiatry. 2015 May;2[5]:381-2).

The findings point to the importance of asking patients – and students and children – about more than just whether they have ever used marijuana. History-taking for marijuana use needs to be comparable to that performed for alcohol use, she said. “I always ask my patients for details about their past and present use but also try to understand why they use (marijuana). When possible, once I know how frequently and what type (of marijuana) they use, I can negotiate some harm-reduction strategy.”

The study is funded by the U.K.’s Medical Research Council and a European Union grant. Dr. Di Forti reports no relevant disclosures.

SAN DIEGO – High-potency marijuana use appears to be associated with an increased risk of a first psychotic episode, based on a case-control study conducted in Europe.

“Daily users of a strong type of cannabis face a significant increase in the probability of developing a psychotic disorder,” reported Marta Di Forti, MD, PhD, MRC, lead author of a study whose preliminary results were presented at the International Congress on Schizophrenia Research.

Dr. Di Forti spawned a media boomlet in 2015 when she and her colleagues raised the prospect of a possible association between so-called “skunk” marijuana and first psychotic episodes. In their study of subjects in London with first-time psychotic episodes and matched population controls, those who had psychotic episodes were three times (adjusted odds ratio: 2.92; 95% confidence interval, 1.52-3.45; P = .001) as likely as controls to have used “skunk” marijuana (Lancet Psychiatry. 2015 Mar;2[3]:233-8).

In the new study, Dr. Di Forti and her colleagues analyzed 1,200 first-incident cases of psychosis that were captured between the years 2010 and 2013 by the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions project (EU-GEI). The researchers compared the cases to 1,300 population-based controls in five unidentified European countries and found that daily users of high-potency marijuana had the highest adjusted odds ratio (4.5-8, statistical significance not available) of a psychotic episode (Schizophr Bull. 2017 Mar:43:S30. doi: 10.1093/schbul/sbx021.078). “This effect is significant even after controlling for other drugs of abuse such as stimulants, tobacco and alcohol, and main sociodemographic confounders,” the researchers wrote in their abstract.

“The biology of cannabis-associated psychosis is still unclear,” Dr. Di Forti said in an interview. “Nevertheless, we know that THC (tetrahydrocannabinol) binds with two receptors called CB1 and CB2. They’re part of the endocannabinoid system, which from uterus onward protects our central nervous systems from insults. It activates on demand if the brain goes on hypoxia or we experience a brain injury.”

“CB1 activation leads to changes in the transmission of both GABA and glutamate. Downstream, they affect the dopamine system, which is biologically linked to psychosis.”

Dr. Di Forti dismissed the idea that people at risk for psychosis are drawn to high-potency marijuana. “Using genetic data, we’ve showed that cannabis users – both cases and controls – did not have a higher genetic load for schizophrenia than those who never used (marijuana),” she said (Lancet Psychiatry. 2015 May;2[5]:381-2).

The findings point to the importance of asking patients – and students and children – about more than just whether they have ever used marijuana. History-taking for marijuana use needs to be comparable to that performed for alcohol use, she said. “I always ask my patients for details about their past and present use but also try to understand why they use (marijuana). When possible, once I know how frequently and what type (of marijuana) they use, I can negotiate some harm-reduction strategy.”

The study is funded by the U.K.’s Medical Research Council and a European Union grant. Dr. Di Forti reports no relevant disclosures.

SAN DIEGO – High-potency marijuana use appears to be associated with an increased risk of a first psychotic episode, based on a case-control study conducted in Europe.

“Daily users of a strong type of cannabis face a significant increase in the probability of developing a psychotic disorder,” reported Marta Di Forti, MD, PhD, MRC, lead author of a study whose preliminary results were presented at the International Congress on Schizophrenia Research.

Dr. Di Forti spawned a media boomlet in 2015 when she and her colleagues raised the prospect of a possible association between so-called “skunk” marijuana and first psychotic episodes. In their study of subjects in London with first-time psychotic episodes and matched population controls, those who had psychotic episodes were three times (adjusted odds ratio: 2.92; 95% confidence interval, 1.52-3.45; P = .001) as likely as controls to have used “skunk” marijuana (Lancet Psychiatry. 2015 Mar;2[3]:233-8).

In the new study, Dr. Di Forti and her colleagues analyzed 1,200 first-incident cases of psychosis that were captured between the years 2010 and 2013 by the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions project (EU-GEI). The researchers compared the cases to 1,300 population-based controls in five unidentified European countries and found that daily users of high-potency marijuana had the highest adjusted odds ratio (4.5-8, statistical significance not available) of a psychotic episode (Schizophr Bull. 2017 Mar:43:S30. doi: 10.1093/schbul/sbx021.078). “This effect is significant even after controlling for other drugs of abuse such as stimulants, tobacco and alcohol, and main sociodemographic confounders,” the researchers wrote in their abstract.

“The biology of cannabis-associated psychosis is still unclear,” Dr. Di Forti said in an interview. “Nevertheless, we know that THC (tetrahydrocannabinol) binds with two receptors called CB1 and CB2. They’re part of the endocannabinoid system, which from uterus onward protects our central nervous systems from insults. It activates on demand if the brain goes on hypoxia or we experience a brain injury.”

“CB1 activation leads to changes in the transmission of both GABA and glutamate. Downstream, they affect the dopamine system, which is biologically linked to psychosis.”

Dr. Di Forti dismissed the idea that people at risk for psychosis are drawn to high-potency marijuana. “Using genetic data, we’ve showed that cannabis users – both cases and controls – did not have a higher genetic load for schizophrenia than those who never used (marijuana),” she said (Lancet Psychiatry. 2015 May;2[5]:381-2).

The findings point to the importance of asking patients – and students and children – about more than just whether they have ever used marijuana. History-taking for marijuana use needs to be comparable to that performed for alcohol use, she said. “I always ask my patients for details about their past and present use but also try to understand why they use (marijuana). When possible, once I know how frequently and what type (of marijuana) they use, I can negotiate some harm-reduction strategy.”

The study is funded by the U.K.’s Medical Research Council and a European Union grant. Dr. Di Forti reports no relevant disclosures.

The diagnosis

Answer: Posttraumatic splenosis

Pathologic examination of the specimen revealed a splenosis showing regular red and white pulp (Figure E). Splenosis is the heterotopic autotransplantation of splenic tissue within the abdominal or pelvic cavity and occurs in 16%–67% of patients with a history of splenic trauma or splenic surgery.1 Nevertheless, hepatic splenosis is rare.2 The literature documents only 16 case reports of hepatic splenosis, although the difficulty of diagnosis could have contributed to underreporting. Although usually harmless, splenosis is a rare cause of bowel obstruction or abdominal pain.

AGA Institute

References

1. Fleming, C.R., Dickson, E.R., Harrison, E.G. Splenosis: autotransplantation of splenic tissue. Am J Med. 1976;61:414-9.
2. D’Angelica, M., Fong, Y., Blumgart, L.H. Isolated hepatic splenosis: first reported case. HPB Surg. 1998;11:39-42.
3. Ohmoto, K., Mimura, N., Iguchi, Y. et al. Percutaneous microwave coagulation therapy for superficial hepatocellular carcinoma on the surface of the liver. Hepatogastroenterology. 2003;50:1547-51.

[email protected]

The diagnosis

Answer: Posttraumatic splenosis

Pathologic examination of the specimen revealed a splenosis showing regular red and white pulp (Figure E). Splenosis is the heterotopic autotransplantation of splenic tissue within the abdominal or pelvic cavity and occurs in 16%–67% of patients with a history of splenic trauma or splenic surgery.1 Nevertheless, hepatic splenosis is rare.2 The literature documents only 16 case reports of hepatic splenosis, although the difficulty of diagnosis could have contributed to underreporting. Although usually harmless, splenosis is a rare cause of bowel obstruction or abdominal pain.

AGA Institute

References

1. Fleming, C.R., Dickson, E.R., Harrison, E.G. Splenosis: autotransplantation of splenic tissue. Am J Med. 1976;61:414-9.
2. D’Angelica, M., Fong, Y., Blumgart, L.H. Isolated hepatic splenosis: first reported case. HPB Surg. 1998;11:39-42.
3. Ohmoto, K., Mimura, N., Iguchi, Y. et al. Percutaneous microwave coagulation therapy for superficial hepatocellular carcinoma on the surface of the liver. Hepatogastroenterology. 2003;50:1547-51.

[email protected]

The diagnosis

Answer: Posttraumatic splenosis

Pathologic examination of the specimen revealed a splenosis showing regular red and white pulp (Figure E). Splenosis is the heterotopic autotransplantation of splenic tissue within the abdominal or pelvic cavity and occurs in 16%–67% of patients with a history of splenic trauma or splenic surgery.1 Nevertheless, hepatic splenosis is rare.2 The literature documents only 16 case reports of hepatic splenosis, although the difficulty of diagnosis could have contributed to underreporting. Although usually harmless, splenosis is a rare cause of bowel obstruction or abdominal pain.

AGA Institute

References

1. Fleming, C.R., Dickson, E.R., Harrison, E.G. Splenosis: autotransplantation of splenic tissue. Am J Med. 1976;61:414-9.
2. D’Angelica, M., Fong, Y., Blumgart, L.H. Isolated hepatic splenosis: first reported case. HPB Surg. 1998;11:39-42.
3. Ohmoto, K., Mimura, N., Iguchi, Y. et al. Percutaneous microwave coagulation therapy for superficial hepatocellular carcinoma on the surface of the liver. Hepatogastroenterology. 2003;50:1547-51.

[email protected]

Q1. CORRECT ANSWER: A

RATIONALE
In patients with a good response to anti-reflux surgery who develop new dysphagia, an upper endoscopy is the test of choice. This will evaluate the structural integrity of the fundoplication, and evaluate for disruption and paraesophageal herniation. The esophagus can be inspected for esophagitis, and dilation of the fundoplication site can be performed. In the absence of heartburn or the original reflux symptoms, empiric acid suppression is not expected to improve the dysphagia. If the endoscopy is negative, esophageal manometry and barium swallow are the next studies of value. A pH study off PPI therapy is performed if recurrent reflux is suspected that does not respond to anti-reflux medications.

REFERENCE
1. Johnson D.A., Younes Z., Hogan W.J. Endoscopic assessment of hiatal hernia repair. Gastrointest Endosc. 2000;52(5):650-9.

Q1. CORRECT ANSWER: A

RATIONALE
In patients with a good response to anti-reflux surgery who develop new dysphagia, an upper endoscopy is the test of choice. This will evaluate the structural integrity of the fundoplication, and evaluate for disruption and paraesophageal herniation. The esophagus can be inspected for esophagitis, and dilation of the fundoplication site can be performed. In the absence of heartburn or the original reflux symptoms, empiric acid suppression is not expected to improve the dysphagia. If the endoscopy is negative, esophageal manometry and barium swallow are the next studies of value. A pH study off PPI therapy is performed if recurrent reflux is suspected that does not respond to anti-reflux medications.

REFERENCE
1. Johnson D.A., Younes Z., Hogan W.J. Endoscopic assessment of hiatal hernia repair. Gastrointest Endosc. 2000;52(5):650-9.

Q1. CORRECT ANSWER: A

RATIONALE
In patients with a good response to anti-reflux surgery who develop new dysphagia, an upper endoscopy is the test of choice. This will evaluate the structural integrity of the fundoplication, and evaluate for disruption and paraesophageal herniation. The esophagus can be inspected for esophagitis, and dilation of the fundoplication site can be performed. In the absence of heartburn or the original reflux symptoms, empiric acid suppression is not expected to improve the dysphagia. If the endoscopy is negative, esophageal manometry and barium swallow are the next studies of value. A pH study off PPI therapy is performed if recurrent reflux is suspected that does not respond to anti-reflux medications.

REFERENCE
1. Johnson D.A., Younes Z., Hogan W.J. Endoscopic assessment of hiatal hernia repair. Gastrointest Endosc. 2000;52(5):650-9.

ATLANTA – 2017 was a banner year for the approval of new drugs to treat hematologic disorders.

At a special interest session at the annual meeting of American Society of Hematology, representatives from the Food and Drug Administration joined forces with clinicians to discuss the use of the newly approved treatments in the real-world setting.

In this video interview, Helen Heslop, MD, provided her perspective on the current use and future directions of three of these treatments: axicabtagene ciloleucel (Yescarta), acalabrutinib (Calquence), and copanlisib (Aliqopa).

“This is extremely exciting,” she said regarding the pace of new approvals for hematologic malignancies.

Axicabtagene ciloleucel, a CAR T-cell product approved in October for the treatment of relapsed/refractory large B-cell lymphoma in adults, is particularly interesting, she said.

“The data shows that if you look at a population of diffuse large B-cell lymphoma patients, that historically have a very poor outcome, there is definitely an impressive response rate and improved survival, compared to the natural history cohort,” said Dr. Heslop of Baylor College of Medicine, Houston.

However, while the findings are encouraging, only 30%-40% are having a durable response, she added.

“So I think there’ll be lots of efforts to try and improve the response rate by combination with other agents such as checkpoint inhibitors or other immunomodulators,” she said.

With respect to the second-generation Bruton’s tyrosine kinase inhibitor acalabrutinib, which was approved in October for adults with mantle cell lymphoma who have been treated with at least one prior therapy, she discussed the potential for improved outcomes and the importance of looking further into its use in patients who have failed ibrutinib therapy, as well as its use in combination with other agents, such as bendamustine and rituximab early in the course of disease.

Copanlisib, a PI3 kinase inhibitor approved in September, is an addition to the armamentarium for adult patients with relapsed follicular lymphoma after two lines of previous therapy.

“It still does have some side effects, as do other drugs in this class, so I think it’s place will still need to be defined,” Dr. Heslop said.

She reported having no relevant financial disclosures.

[email protected]

ATLANTA – 2017 was a banner year for the approval of new drugs to treat hematologic disorders.

At a special interest session at the annual meeting of American Society of Hematology, representatives from the Food and Drug Administration joined forces with clinicians to discuss the use of the newly approved treatments in the real-world setting.

In this video interview, Helen Heslop, MD, provided her perspective on the current use and future directions of three of these treatments: axicabtagene ciloleucel (Yescarta), acalabrutinib (Calquence), and copanlisib (Aliqopa).

“This is extremely exciting,” she said regarding the pace of new approvals for hematologic malignancies.

Axicabtagene ciloleucel, a CAR T-cell product approved in October for the treatment of relapsed/refractory large B-cell lymphoma in adults, is particularly interesting, she said.

“The data shows that if you look at a population of diffuse large B-cell lymphoma patients, that historically have a very poor outcome, there is definitely an impressive response rate and improved survival, compared to the natural history cohort,” said Dr. Heslop of Baylor College of Medicine, Houston.

However, while the findings are encouraging, only 30%-40% are having a durable response, she added.

“So I think there’ll be lots of efforts to try and improve the response rate by combination with other agents such as checkpoint inhibitors or other immunomodulators,” she said.

With respect to the second-generation Bruton’s tyrosine kinase inhibitor acalabrutinib, which was approved in October for adults with mantle cell lymphoma who have been treated with at least one prior therapy, she discussed the potential for improved outcomes and the importance of looking further into its use in patients who have failed ibrutinib therapy, as well as its use in combination with other agents, such as bendamustine and rituximab early in the course of disease.

Copanlisib, a PI3 kinase inhibitor approved in September, is an addition to the armamentarium for adult patients with relapsed follicular lymphoma after two lines of previous therapy.

“It still does have some side effects, as do other drugs in this class, so I think it’s place will still need to be defined,” Dr. Heslop said.

She reported having no relevant financial disclosures.

[email protected]

ATLANTA – 2017 was a banner year for the approval of new drugs to treat hematologic disorders.

At a special interest session at the annual meeting of American Society of Hematology, representatives from the Food and Drug Administration joined forces with clinicians to discuss the use of the newly approved treatments in the real-world setting.

In this video interview, Helen Heslop, MD, provided her perspective on the current use and future directions of three of these treatments: axicabtagene ciloleucel (Yescarta), acalabrutinib (Calquence), and copanlisib (Aliqopa).

“This is extremely exciting,” she said regarding the pace of new approvals for hematologic malignancies.

Axicabtagene ciloleucel, a CAR T-cell product approved in October for the treatment of relapsed/refractory large B-cell lymphoma in adults, is particularly interesting, she said.

“The data shows that if you look at a population of diffuse large B-cell lymphoma patients, that historically have a very poor outcome, there is definitely an impressive response rate and improved survival, compared to the natural history cohort,” said Dr. Heslop of Baylor College of Medicine, Houston.

However, while the findings are encouraging, only 30%-40% are having a durable response, she added.

“So I think there’ll be lots of efforts to try and improve the response rate by combination with other agents such as checkpoint inhibitors or other immunomodulators,” she said.

With respect to the second-generation Bruton’s tyrosine kinase inhibitor acalabrutinib, which was approved in October for adults with mantle cell lymphoma who have been treated with at least one prior therapy, she discussed the potential for improved outcomes and the importance of looking further into its use in patients who have failed ibrutinib therapy, as well as its use in combination with other agents, such as bendamustine and rituximab early in the course of disease.

Copanlisib, a PI3 kinase inhibitor approved in September, is an addition to the armamentarium for adult patients with relapsed follicular lymphoma after two lines of previous therapy.

“It still does have some side effects, as do other drugs in this class, so I think it’s place will still need to be defined,” Dr. Heslop said.

She reported having no relevant financial disclosures.

[email protected]

Take-Home Points

• PQ is easily mistaken for a PB tear.
• PQ is best identified on MRI, but commonly missed.
• For symptomatic cases, excision is the best treatment.
• Consider PQ in patients with chronic ankle pain, swelling, and/or instability.

The peroneus quartus (PQ) is an accessory muscle arising from the leg’s lateral compartment, which typically contains the peroneus longus (PL) and the peroneus brevis (PB). The many cadaveric studies that have been conducted indicate a general population prevalence ranging from 6.6% to 23%.¹ Radiographic studies, including magnetic resonance imaging (MRI) and ultrasonography, have shown a similar prevalence.² Although the PQ is asymptomatic in most cases, it may compromise the space of the superior peroneal tunnel and cause problems, including ankle pain, PB tear, subluxation of peroneal tendons, tendinous calcification, painful hypertrophy of retrotrochlear eminence, and recurrent hematomas.^1,3-5 Given its differing anatomy, the PQ variously has been referred to as peroneocalcaneus externum, peroneocuboideus, long peroneal tendon, and peroneoperoneolongus.¹ 

Although the PQ’s origin and insertion differ between subjects, the most common origin is the muscle fibers of the PB, and the most common insertion is the retrotrochlear eminence of the calcaneum.³

We report a case of peroneal tendon pathology that was initially thought to be caused primarily by impingement of a large osteochondroma on the tendons, but was later thought to be caused in part by a PQ and a split PB tendon seen only at the time of the second operation. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 16-year-old boy with an osteochondroma of the right distal fibula presented to clinic with the chief complaint of lateral right ankle pain. A “sharp” pain accompanied by audible “popping” occurred with ankle motion. Medical history was significant only for non-Hodgkin lymphoma treated with bone marrow transplantation and whole body radiation at a young age. Physical examination revealed a palpable exostosis of the distal right fibula and associated ankle swelling.

One year after surgery, the patient returned with recurring right ankle pain and audible popping during ankle movement. There was no appreciable peroneal tendon subluxation on physical examination. Repeat imaging of the ankle showed no recurrence of the osteochondroma (Figure 2).

Discussion

Absence of a PQ muscle in simian and prosimian species suggests that the PQ represents an evolutionary adaptation to evert the lateral foot and improve bipedal gait. Although the 3 peroneal (PL, PB, peroneus tertius [PT]) muscles evert the middle part of the lateral border of the foot, the PQ inserts on the retrotrochlear eminence, which everts the posterior part of the lateral border of the foot.^1,6 The PQ has often been described as a variation of the PB. The PQ may also stabilize the ankle and reduce the energy required for walking. A similar functional adaptation has been proposed for the PT, which dorsiflexes at the ankle. Although presence of a PT also varies in the population, its occurrence does not correlate with presence of a PQ. In people with PQ muscles, there is an 83% to 95% incidence of also having PT muscles.⁷

PQ prevalence has ranged from 6.6% to 23% in cadaver studies² and from 7% to 17% in radiologic studies.¹ To better evaluate prevalence, Yammine² performed a meta-analysis of data from 46 studies (cadaveric dissection, MRI, ultrasonography) and 3928 legs and found an overall incidence of 10.2% and a higher incidence in the Indian population than in other races. Another study found no correlation between PQ presence and sex.⁷

MRI is the best imaging modality for assessing for PQ but must be performed specifically for this anatomical variation. Axial images may show a fat pad separating the PQ muscle from the PB muscle.⁸ On imaging, a PQ muscle can be mistaken for a peroneal tendon tear. A feature that helps in distinguishing the 2 is location; the PQ typically is found posterior and medial to the PL and PB tendons, whereas PB tears are anterior to the retromalleolar groove.² Presence of a PQ muscle may be missed on initial MRI, as occurred in our patient’s case. Zammit and Singh³ reviewed 80 leg MRIs and found 6 PQs. Only 1 of the 6 reports described the PQ as an “atypical appearance of peroneus brevis [that] appears to be made up of more than one tendon.”

Surgical excision is often adequate treatment for a symptomatic PQ. If the PQ muscle is small and symptomatic from pressure to the muscle mass, a short fasciotomy may be performed.⁹ More commonly, complete excision of the accessory muscle is required. Although the PQ muscle is usually asymptomatic, it should be considered in cases of chronic ankle pain, swelling, or instability; recurrent hematomas; and peroneal tendon subluxation or tears.^5,7

Our patient’s diagnosis was initially overlooked because of an osteochondroma in the region of interest. It remains unclear whether his pain was caused by the PQ itself or, more likely, from the PB tear. It is thought that the accessory muscle adds bulk to the peroneal tunnel, predisposing to peroneal pathology, such as muscle tears and tendon subluxation. Regardless, advanced imaging performed before the index procedure, along with a general understanding of the PQ and its classic MRI findings, may have prevented the repeat operation in this case.

The PQ muscle is a rare but sometimes missed potential etiology of ankle pain and tendon subluxation. In our patient’s case, the most obvious abnormality, an osteochondroma, may have masked the true cause.

Take-Home Points

• PQ is easily mistaken for a PB tear.
• PQ is best identified on MRI, but commonly missed.
• For symptomatic cases, excision is the best treatment.
• Consider PQ in patients with chronic ankle pain, swelling, and/or instability.

The peroneus quartus (PQ) is an accessory muscle arising from the leg’s lateral compartment, which typically contains the peroneus longus (PL) and the peroneus brevis (PB). The many cadaveric studies that have been conducted indicate a general population prevalence ranging from 6.6% to 23%.¹ Radiographic studies, including magnetic resonance imaging (MRI) and ultrasonography, have shown a similar prevalence.² Although the PQ is asymptomatic in most cases, it may compromise the space of the superior peroneal tunnel and cause problems, including ankle pain, PB tear, subluxation of peroneal tendons, tendinous calcification, painful hypertrophy of retrotrochlear eminence, and recurrent hematomas.^1,3-5 Given its differing anatomy, the PQ variously has been referred to as peroneocalcaneus externum, peroneocuboideus, long peroneal tendon, and peroneoperoneolongus.¹ 

Although the PQ’s origin and insertion differ between subjects, the most common origin is the muscle fibers of the PB, and the most common insertion is the retrotrochlear eminence of the calcaneum.³

We report a case of peroneal tendon pathology that was initially thought to be caused primarily by impingement of a large osteochondroma on the tendons, but was later thought to be caused in part by a PQ and a split PB tendon seen only at the time of the second operation. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 16-year-old boy with an osteochondroma of the right distal fibula presented to clinic with the chief complaint of lateral right ankle pain. A “sharp” pain accompanied by audible “popping” occurred with ankle motion. Medical history was significant only for non-Hodgkin lymphoma treated with bone marrow transplantation and whole body radiation at a young age. Physical examination revealed a palpable exostosis of the distal right fibula and associated ankle swelling.

One year after surgery, the patient returned with recurring right ankle pain and audible popping during ankle movement. There was no appreciable peroneal tendon subluxation on physical examination. Repeat imaging of the ankle showed no recurrence of the osteochondroma (Figure 2).

Discussion

Absence of a PQ muscle in simian and prosimian species suggests that the PQ represents an evolutionary adaptation to evert the lateral foot and improve bipedal gait. Although the 3 peroneal (PL, PB, peroneus tertius [PT]) muscles evert the middle part of the lateral border of the foot, the PQ inserts on the retrotrochlear eminence, which everts the posterior part of the lateral border of the foot.^1,6 The PQ has often been described as a variation of the PB. The PQ may also stabilize the ankle and reduce the energy required for walking. A similar functional adaptation has been proposed for the PT, which dorsiflexes at the ankle. Although presence of a PT also varies in the population, its occurrence does not correlate with presence of a PQ. In people with PQ muscles, there is an 83% to 95% incidence of also having PT muscles.⁷

PQ prevalence has ranged from 6.6% to 23% in cadaver studies² and from 7% to 17% in radiologic studies.¹ To better evaluate prevalence, Yammine² performed a meta-analysis of data from 46 studies (cadaveric dissection, MRI, ultrasonography) and 3928 legs and found an overall incidence of 10.2% and a higher incidence in the Indian population than in other races. Another study found no correlation between PQ presence and sex.⁷

MRI is the best imaging modality for assessing for PQ but must be performed specifically for this anatomical variation. Axial images may show a fat pad separating the PQ muscle from the PB muscle.⁸ On imaging, a PQ muscle can be mistaken for a peroneal tendon tear. A feature that helps in distinguishing the 2 is location; the PQ typically is found posterior and medial to the PL and PB tendons, whereas PB tears are anterior to the retromalleolar groove.² Presence of a PQ muscle may be missed on initial MRI, as occurred in our patient’s case. Zammit and Singh³ reviewed 80 leg MRIs and found 6 PQs. Only 1 of the 6 reports described the PQ as an “atypical appearance of peroneus brevis [that] appears to be made up of more than one tendon.”

Surgical excision is often adequate treatment for a symptomatic PQ. If the PQ muscle is small and symptomatic from pressure to the muscle mass, a short fasciotomy may be performed.⁹ More commonly, complete excision of the accessory muscle is required. Although the PQ muscle is usually asymptomatic, it should be considered in cases of chronic ankle pain, swelling, or instability; recurrent hematomas; and peroneal tendon subluxation or tears.^5,7

Our patient’s diagnosis was initially overlooked because of an osteochondroma in the region of interest. It remains unclear whether his pain was caused by the PQ itself or, more likely, from the PB tear. It is thought that the accessory muscle adds bulk to the peroneal tunnel, predisposing to peroneal pathology, such as muscle tears and tendon subluxation. Regardless, advanced imaging performed before the index procedure, along with a general understanding of the PQ and its classic MRI findings, may have prevented the repeat operation in this case.

The PQ muscle is a rare but sometimes missed potential etiology of ankle pain and tendon subluxation. In our patient’s case, the most obvious abnormality, an osteochondroma, may have masked the true cause.

Take-Home Points

• PQ is easily mistaken for a PB tear.
• PQ is best identified on MRI, but commonly missed.
• For symptomatic cases, excision is the best treatment.
• Consider PQ in patients with chronic ankle pain, swelling, and/or instability.

The peroneus quartus (PQ) is an accessory muscle arising from the leg’s lateral compartment, which typically contains the peroneus longus (PL) and the peroneus brevis (PB). The many cadaveric studies that have been conducted indicate a general population prevalence ranging from 6.6% to 23%.¹ Radiographic studies, including magnetic resonance imaging (MRI) and ultrasonography, have shown a similar prevalence.² Although the PQ is asymptomatic in most cases, it may compromise the space of the superior peroneal tunnel and cause problems, including ankle pain, PB tear, subluxation of peroneal tendons, tendinous calcification, painful hypertrophy of retrotrochlear eminence, and recurrent hematomas.^1,3-5 Given its differing anatomy, the PQ variously has been referred to as peroneocalcaneus externum, peroneocuboideus, long peroneal tendon, and peroneoperoneolongus.¹ 

Although the PQ’s origin and insertion differ between subjects, the most common origin is the muscle fibers of the PB, and the most common insertion is the retrotrochlear eminence of the calcaneum.³

We report a case of peroneal tendon pathology that was initially thought to be caused primarily by impingement of a large osteochondroma on the tendons, but was later thought to be caused in part by a PQ and a split PB tendon seen only at the time of the second operation. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 16-year-old boy with an osteochondroma of the right distal fibula presented to clinic with the chief complaint of lateral right ankle pain. A “sharp” pain accompanied by audible “popping” occurred with ankle motion. Medical history was significant only for non-Hodgkin lymphoma treated with bone marrow transplantation and whole body radiation at a young age. Physical examination revealed a palpable exostosis of the distal right fibula and associated ankle swelling.

One year after surgery, the patient returned with recurring right ankle pain and audible popping during ankle movement. There was no appreciable peroneal tendon subluxation on physical examination. Repeat imaging of the ankle showed no recurrence of the osteochondroma (Figure 2).

Discussion

Absence of a PQ muscle in simian and prosimian species suggests that the PQ represents an evolutionary adaptation to evert the lateral foot and improve bipedal gait. Although the 3 peroneal (PL, PB, peroneus tertius [PT]) muscles evert the middle part of the lateral border of the foot, the PQ inserts on the retrotrochlear eminence, which everts the posterior part of the lateral border of the foot.^1,6 The PQ has often been described as a variation of the PB. The PQ may also stabilize the ankle and reduce the energy required for walking. A similar functional adaptation has been proposed for the PT, which dorsiflexes at the ankle. Although presence of a PT also varies in the population, its occurrence does not correlate with presence of a PQ. In people with PQ muscles, there is an 83% to 95% incidence of also having PT muscles.⁷

PQ prevalence has ranged from 6.6% to 23% in cadaver studies² and from 7% to 17% in radiologic studies.¹ To better evaluate prevalence, Yammine² performed a meta-analysis of data from 46 studies (cadaveric dissection, MRI, ultrasonography) and 3928 legs and found an overall incidence of 10.2% and a higher incidence in the Indian population than in other races. Another study found no correlation between PQ presence and sex.⁷

MRI is the best imaging modality for assessing for PQ but must be performed specifically for this anatomical variation. Axial images may show a fat pad separating the PQ muscle from the PB muscle.⁸ On imaging, a PQ muscle can be mistaken for a peroneal tendon tear. A feature that helps in distinguishing the 2 is location; the PQ typically is found posterior and medial to the PL and PB tendons, whereas PB tears are anterior to the retromalleolar groove.² Presence of a PQ muscle may be missed on initial MRI, as occurred in our patient’s case. Zammit and Singh³ reviewed 80 leg MRIs and found 6 PQs. Only 1 of the 6 reports described the PQ as an “atypical appearance of peroneus brevis [that] appears to be made up of more than one tendon.”

Surgical excision is often adequate treatment for a symptomatic PQ. If the PQ muscle is small and symptomatic from pressure to the muscle mass, a short fasciotomy may be performed.⁹ More commonly, complete excision of the accessory muscle is required. Although the PQ muscle is usually asymptomatic, it should be considered in cases of chronic ankle pain, swelling, or instability; recurrent hematomas; and peroneal tendon subluxation or tears.^5,7

Our patient’s diagnosis was initially overlooked because of an osteochondroma in the region of interest. It remains unclear whether his pain was caused by the PQ itself or, more likely, from the PB tear. It is thought that the accessory muscle adds bulk to the peroneal tunnel, predisposing to peroneal pathology, such as muscle tears and tendon subluxation. Regardless, advanced imaging performed before the index procedure, along with a general understanding of the PQ and its classic MRI findings, may have prevented the repeat operation in this case.

The PQ muscle is a rare but sometimes missed potential etiology of ankle pain and tendon subluxation. In our patient’s case, the most obvious abnormality, an osteochondroma, may have masked the true cause.

State of Hospital Medicine Survey opens next month!

The 2018 State of Hospital Medicine Survey will begin in January and last through March with the release of the report in September 2018. Whether you are in a hospital medicine group in an academic or community setting, employed by a hospital or health system, a management company, a private group, or you serve adult or pediatric patients (or both), we need your participation.

Help us help you have the most comprehensive, up-to-date landscape of hospital medicine at your fingertips by participating. As a thank-you for your participation, your group will receive a free copy of the report. Sign up at hospitalmedicine.org/survey.
 

Apply for SHM’s MARQUIS Med Rec Collaborative kicking off in February 2018

SHM’s MARQUIS Med Rec Collaborative is designed to help hospitals across the United States implement evidence-based best practice medication reconciliation process change and improvement. The collaborative is a 14-month program, spanning from prelaunch to completion.

The staff has the expertise and experience of having completed two previous mentored implementation studies, involving 23 sites and thousands of patients. The collaborative also offers numerous resources, including training materials, project management and process improvement tools for hospitals to use to adapt for their needs to improve the medication reconciliation process. Visit hospitalmedicine.org/MARQUISrecruit to learn more.
 

Get engaged with public policy

Health care legislation is constantly evolving, and hospitalists play an important role in advocating for hospitalized patients and the hospital medicine movement. SHM is an active voice in many conversations on policy development and reform. Visit hospitalmedicine.org and sign up for the Grassroots Network to stay updated on developments in health care policy, share your experiences with health care programs and participate in policy forums.

Develop your career at Hospital Medicine 2018

Don’t miss SHM’s Annual Conference, Hospital Medicine 2018, to be held April 8-11, 2018. in Orlando. This year, the program was created to help you develop your hospital medicine career, no matter what stage you are in. Two new tracks include Seasoning Your Career and the Career Development Workshops.

Seasoning Your Career focuses on didactics designed to augment those committed to a career in hospital medicine, including topics such as career growth and development, resiliency, work-life balance, and how practical work matters such as schedules affect your career.

The new Career Development Workshops track includes six sessions that aim to help you use skills that will advance your career, such as: Leadership Essentials for Success in Hospital Medicine; Being Female in Hospital Medicine: Overcoming Individual and Institutional Barriers in the Workplace; Do You Have a Minute to Talk? Peer-to-Peer Feedback, and more.

Just starting out in hospital medicine? Back by popular demand, The Early-Career Hospitalists track has been designed for new hospitalists, resident physicians, and medical students interested in pursuing a career in hospital medicine. Designed by SHM’s Physicians-in-Training Committee, which includes nationally recognized hospitalists with expertise in scholarship, career development and medical education, this track aims to inspire future hospitalist leaders.

Visit shmannualconference.org/schedule to learn more.
 

Two new modules debut on SHM’s Learning Portal

SHM members have access to free continuing medical education (CME) and Maintenance of Certification (MOC) points with the SHM Learning Portal. Don’t miss two new modules: Role of the Medical Consultant and Anesthesia for Internists.

Medical consultation is an important clinical component for most hospitalists. Today, hospitalists also are asked to provide both “curbside” advice and more comprehensive comanagement of medical problems. Hospitalists who are effective consultants communicate skillfully and act professionally. The Role of the Medical Consultant module describes the different roles that hospitalists can perform as medical consultants and provides strategies for improving communications and referring physician satisfaction.

Looking for up-to-date information about surgical anesthesia? The Anesthesia for Internists module discusses the basic forms of surgical anesthesia and contraindications to each, as well as the most commonly used anesthetic drugs, their mechanisms of actions, and side effects.

Both modules are free for SHM members and $45.00 per module for nonmembers. Earn 2 AMA PRA Category 1 Credits™ and 2 MOC points per each module. Visit shmlearningportal.org to get started today.
 

Not a member? Join the movement today

More than 15,000 members have joined SHM to show their commitment to revolutionizing patient care. As a member, you will be connected with a wealth of opportunities designed to help you grow professionally, network with colleagues nationwide, and shape the practice of hospital medicine. See a full list of member benefits or become a member today at hospitalmedicine.org/join.

Join a chapter and connect to your local hospital medicine community

SHM hosts more than 50 local chapters nationwide to encourage networking, collaboration, and innovation within the hospital medicine community. Getting involved with your local chapter allows you to share knowledge, engage with colleagues, and stay current on the latest developments in hospital medicine.

Visit hospitalmedicine.org/chapters to find a chapter in your area.

Mr. Radler is marketing communications manager at the Society of Hospital Medicine.

State of Hospital Medicine Survey opens next month!

The 2018 State of Hospital Medicine Survey will begin in January and last through March with the release of the report in September 2018. Whether you are in a hospital medicine group in an academic or community setting, employed by a hospital or health system, a management company, a private group, or you serve adult or pediatric patients (or both), we need your participation.

Help us help you have the most comprehensive, up-to-date landscape of hospital medicine at your fingertips by participating. As a thank-you for your participation, your group will receive a free copy of the report. Sign up at hospitalmedicine.org/survey.
 

Apply for SHM’s MARQUIS Med Rec Collaborative kicking off in February 2018

SHM’s MARQUIS Med Rec Collaborative is designed to help hospitals across the United States implement evidence-based best practice medication reconciliation process change and improvement. The collaborative is a 14-month program, spanning from prelaunch to completion.

The staff has the expertise and experience of having completed two previous mentored implementation studies, involving 23 sites and thousands of patients. The collaborative also offers numerous resources, including training materials, project management and process improvement tools for hospitals to use to adapt for their needs to improve the medication reconciliation process. Visit hospitalmedicine.org/MARQUISrecruit to learn more.
 

Get engaged with public policy

Health care legislation is constantly evolving, and hospitalists play an important role in advocating for hospitalized patients and the hospital medicine movement. SHM is an active voice in many conversations on policy development and reform. Visit hospitalmedicine.org and sign up for the Grassroots Network to stay updated on developments in health care policy, share your experiences with health care programs and participate in policy forums.

Develop your career at Hospital Medicine 2018

Don’t miss SHM’s Annual Conference, Hospital Medicine 2018, to be held April 8-11, 2018. in Orlando. This year, the program was created to help you develop your hospital medicine career, no matter what stage you are in. Two new tracks include Seasoning Your Career and the Career Development Workshops.

Seasoning Your Career focuses on didactics designed to augment those committed to a career in hospital medicine, including topics such as career growth and development, resiliency, work-life balance, and how practical work matters such as schedules affect your career.

The new Career Development Workshops track includes six sessions that aim to help you use skills that will advance your career, such as: Leadership Essentials for Success in Hospital Medicine; Being Female in Hospital Medicine: Overcoming Individual and Institutional Barriers in the Workplace; Do You Have a Minute to Talk? Peer-to-Peer Feedback, and more.

Just starting out in hospital medicine? Back by popular demand, The Early-Career Hospitalists track has been designed for new hospitalists, resident physicians, and medical students interested in pursuing a career in hospital medicine. Designed by SHM’s Physicians-in-Training Committee, which includes nationally recognized hospitalists with expertise in scholarship, career development and medical education, this track aims to inspire future hospitalist leaders.

Visit shmannualconference.org/schedule to learn more.
 

Two new modules debut on SHM’s Learning Portal

SHM members have access to free continuing medical education (CME) and Maintenance of Certification (MOC) points with the SHM Learning Portal. Don’t miss two new modules: Role of the Medical Consultant and Anesthesia for Internists.

Medical consultation is an important clinical component for most hospitalists. Today, hospitalists also are asked to provide both “curbside” advice and more comprehensive comanagement of medical problems. Hospitalists who are effective consultants communicate skillfully and act professionally. The Role of the Medical Consultant module describes the different roles that hospitalists can perform as medical consultants and provides strategies for improving communications and referring physician satisfaction.

Looking for up-to-date information about surgical anesthesia? The Anesthesia for Internists module discusses the basic forms of surgical anesthesia and contraindications to each, as well as the most commonly used anesthetic drugs, their mechanisms of actions, and side effects.

Both modules are free for SHM members and $45.00 per module for nonmembers. Earn 2 AMA PRA Category 1 Credits™ and 2 MOC points per each module. Visit shmlearningportal.org to get started today.
 

Not a member? Join the movement today

More than 15,000 members have joined SHM to show their commitment to revolutionizing patient care. As a member, you will be connected with a wealth of opportunities designed to help you grow professionally, network with colleagues nationwide, and shape the practice of hospital medicine. See a full list of member benefits or become a member today at hospitalmedicine.org/join.

Join a chapter and connect to your local hospital medicine community

SHM hosts more than 50 local chapters nationwide to encourage networking, collaboration, and innovation within the hospital medicine community. Getting involved with your local chapter allows you to share knowledge, engage with colleagues, and stay current on the latest developments in hospital medicine.

Visit hospitalmedicine.org/chapters to find a chapter in your area.

Mr. Radler is marketing communications manager at the Society of Hospital Medicine.

State of Hospital Medicine Survey opens next month!

The 2018 State of Hospital Medicine Survey will begin in January and last through March with the release of the report in September 2018. Whether you are in a hospital medicine group in an academic or community setting, employed by a hospital or health system, a management company, a private group, or you serve adult or pediatric patients (or both), we need your participation.

Help us help you have the most comprehensive, up-to-date landscape of hospital medicine at your fingertips by participating. As a thank-you for your participation, your group will receive a free copy of the report. Sign up at hospitalmedicine.org/survey.
 

Apply for SHM’s MARQUIS Med Rec Collaborative kicking off in February 2018

SHM’s MARQUIS Med Rec Collaborative is designed to help hospitals across the United States implement evidence-based best practice medication reconciliation process change and improvement. The collaborative is a 14-month program, spanning from prelaunch to completion.

The staff has the expertise and experience of having completed two previous mentored implementation studies, involving 23 sites and thousands of patients. The collaborative also offers numerous resources, including training materials, project management and process improvement tools for hospitals to use to adapt for their needs to improve the medication reconciliation process. Visit hospitalmedicine.org/MARQUISrecruit to learn more.
 

Get engaged with public policy

Health care legislation is constantly evolving, and hospitalists play an important role in advocating for hospitalized patients and the hospital medicine movement. SHM is an active voice in many conversations on policy development and reform. Visit hospitalmedicine.org and sign up for the Grassroots Network to stay updated on developments in health care policy, share your experiences with health care programs and participate in policy forums.

Develop your career at Hospital Medicine 2018

Don’t miss SHM’s Annual Conference, Hospital Medicine 2018, to be held April 8-11, 2018. in Orlando. This year, the program was created to help you develop your hospital medicine career, no matter what stage you are in. Two new tracks include Seasoning Your Career and the Career Development Workshops.

Seasoning Your Career focuses on didactics designed to augment those committed to a career in hospital medicine, including topics such as career growth and development, resiliency, work-life balance, and how practical work matters such as schedules affect your career.

The new Career Development Workshops track includes six sessions that aim to help you use skills that will advance your career, such as: Leadership Essentials for Success in Hospital Medicine; Being Female in Hospital Medicine: Overcoming Individual and Institutional Barriers in the Workplace; Do You Have a Minute to Talk? Peer-to-Peer Feedback, and more.

Just starting out in hospital medicine? Back by popular demand, The Early-Career Hospitalists track has been designed for new hospitalists, resident physicians, and medical students interested in pursuing a career in hospital medicine. Designed by SHM’s Physicians-in-Training Committee, which includes nationally recognized hospitalists with expertise in scholarship, career development and medical education, this track aims to inspire future hospitalist leaders.

Visit shmannualconference.org/schedule to learn more.
 

Two new modules debut on SHM’s Learning Portal

SHM members have access to free continuing medical education (CME) and Maintenance of Certification (MOC) points with the SHM Learning Portal. Don’t miss two new modules: Role of the Medical Consultant and Anesthesia for Internists.

Medical consultation is an important clinical component for most hospitalists. Today, hospitalists also are asked to provide both “curbside” advice and more comprehensive comanagement of medical problems. Hospitalists who are effective consultants communicate skillfully and act professionally. The Role of the Medical Consultant module describes the different roles that hospitalists can perform as medical consultants and provides strategies for improving communications and referring physician satisfaction.

Looking for up-to-date information about surgical anesthesia? The Anesthesia for Internists module discusses the basic forms of surgical anesthesia and contraindications to each, as well as the most commonly used anesthetic drugs, their mechanisms of actions, and side effects.

Both modules are free for SHM members and $45.00 per module for nonmembers. Earn 2 AMA PRA Category 1 Credits™ and 2 MOC points per each module. Visit shmlearningportal.org to get started today.
 

Not a member? Join the movement today

More than 15,000 members have joined SHM to show their commitment to revolutionizing patient care. As a member, you will be connected with a wealth of opportunities designed to help you grow professionally, network with colleagues nationwide, and shape the practice of hospital medicine. See a full list of member benefits or become a member today at hospitalmedicine.org/join.

Join a chapter and connect to your local hospital medicine community

SHM hosts more than 50 local chapters nationwide to encourage networking, collaboration, and innovation within the hospital medicine community. Getting involved with your local chapter allows you to share knowledge, engage with colleagues, and stay current on the latest developments in hospital medicine.

Visit hospitalmedicine.org/chapters to find a chapter in your area.

Mr. Radler is marketing communications manager at the Society of Hospital Medicine.

Take-Home Points

• Metastatic disease of the tibia is a rare but significant event in a subset of patients.
• Cancer histologies with historically “acral” spread may not apply to tibial disease.
• Patients with leg pain and any cancer diagnosis should be worked up for tibial metastases.
• Tibial disease is probably a late manifestation, and early detection may indicate late diagnosis of malignancy.
• The ultimate surgical plan for these patients should be a patient-centered multidisciplinary decision making process.

Metastatic dissemination to bones is common in advanced cancer stages and affects the axial and appendicular skeleton.^1-4 The appendicular skeleton bones most often involved are the proximal femur and the proximal humerus.^5,6 The tibia is involved third most often but is comparatively rarely affected.^4-6 Metastatic involvement distal to the knee or elbow is more typical of advanced disease.^1,3 Distal appendicular lesions are called acral metastases, but the term is inconsistently used and may refer to lesions either distal to the knee and elbow or distal to the ankle and wrist. Regardless of terminology, tibia lesions are uncommon and not well described.^1,4,7,8

The tibia is the primary weight-bearing leg bone. Metastatic tibia lesions may cause pain and instability and impair mobility. Although distal skeletal dissemination often presents late in advanced disease in patients with relatively poor prognoses, in some cases early surgical intervention is indicated for pain relief, increased mobility, and improved quality of life.^4,8-10

Materials and Methods

Our Institutional Review Board approved this single-institution retrospective study. We used proprietary research software (Clinical Looking Glass) to identify eligible patients treated between 2000 and 2013. The software was used to search all radiology and pathology reports for the term tibia or any variation (eg, tibial) and metastasis or any variation (eg, metastatic). The software was then used to search by Current Procedural Terminology code for any patients treated with intramedullary nail (IMN) or another tibial fixation method. This list was cross-referenced with the list of patients originally identified to help ensure that all eligible patients were identified. 

Inclusion criteria were known malignancy and imaging or biopsy evidence of a metastatic tibia lesion. Treatment strategies for patients with metastatic disease and patients with multiple myeloma are sometimes considered together because of similar goals and methodologies. We specifically excluded patients with multiple myeloma in order to more accurately characterize the natural history of metastatic disease and the timing of metastatic development and to report on a more homogeneous population. Patients were excluded if their electronic medical records were inadequate in establishing a diagnosis.

Demographic and pathology data were collected directly from the institutional electronic medical records system. Dr. Geller and Dr. Greenbaum used Centricity software (General Electric Healthcare) to review all imaging on medical diagnostic display monitors. If their interpretation differed from that in the radiology report, or if clarification was needed, the study was sent to Dr. Thornhill, the institution’s director of musculoskeletal radiology, for review and interpretation. Investigated radiographic characteristics included location, cortical breakthrough, presence of fracture, and size (if advanced imaging was available). Surgical interventions were recorded from reviews of operative reports and postoperative imaging studies.

Time to metastasis was defined as number of days from diagnosis of malignancy to diagnosis of tibial osseous spread. Date of diagnosis of malignancy was the date that a biopsy or other confirmatory test was performed. In cases in which that date was unavailable, an imaging study consistent with disease or a clinical note documenting the known diagnosis date was used instead. When only month and year (ie, not an exact date) of diagnosis were available, the 15th of the month was used as an estimate. Of the 36 patients, 4 had records insufficient for establishing date of diagnosis. The first date of any imaging study confirming (or suggestive of) a metastatic lesion of the tibia was used as the date of tibial metastasis. 

Many patients had osseous lesions at sites other than the tibiae. These lesions were noted on review of imaging studies, screening examinations, and physicians’ clinical notes. Widespread disease was defined as including both axial and appendicular lesions, and lesions of the tibiae.

Tibia lesion presentation was recorded as either symptomatic or incidental. If the tibiae were imaged for pain, including posttraumatic pain, the presentation was symptomatic. If a lesion was identified on staging examination (eg, bone or positron emission tomography scan), or if the tibiae were imaged for another reason, the presentation was incidental.

Results

Demographics

Thirty-six patients had 43 affected tibiae. Sixteen male patients (44.4% of the total) had 19 (44.2%) of the affected tibiae, and 20 female patients (55.6%) had the other 24 affected tibiae (55.8%). Mean age was 63.5 years for all patients (range, 6-95 years), 68.1 years for males, and 59.8 years for females. Of the 36 patients, 32 (88.9%) were over age 40 years (Table). All patients had radiographic evidence of ≥1 tibia lesion, and 6 (16.7%) also had biopsy-proven metastatic disease of the tibia.

Tumor Characteristics

There were 12 different primary neoplasms (Table). The most common were prostate cancer (7 patients, 19.4%; 10 tibiae, 23.3%), breast cancer (7 patients, 19.4%; 9 tibiae, 20.9%), and lung cancer (7 patients, 19.4%; 7 tibiae, 16.3%). For males, the most common diagnoses were prostate cancer (7 cases, 43.8% of males) and diffuse large B-cell lymphoma and lung cancer (3 cases and 18.8% of males each). For females, the most common diagnoses were breast cancer (7 cases, 35.0% of females) and lung cancer (4 cases, 20.0% of females). 

Most of the lesions were proximal (31 tibiae, 72.1%), followed by diaphyseal (7, 16.3%) and distal (2, 4.7%) (Table). Three tibiae (7.0%) were entirely involved, but 1 of these was more affected at the distal end. One tibia had 2 lesions, 1 proximal and 1 distal.

Time to Metastasis, Other Osseous Disease

Mean time from diagnosis of malignancy to diagnosis of osseous disease of the tibia was 1282 days (range, 0-3708 days) (Table). Of the 36 patients, 32 (88.9%) had other metastatic lesions, 3 (8.3%) had isolated tibia lesions, and 1 (2.8%) had a medical record insufficient for establishing lesion status (isolated or not). Of the 32 patients with known other osseous metastases, 14 (43.8%) had widespread (axial and additional appendicular) disease, and 3 (9.4%) had additional lesions only distal to the identified tibial metastases.

Clinical Presentation

Of the 36 lesions, 18 (50%) were asymptomatic and were found on screening examinations, 17 (47.2%) presented with pain, and 1 (2.8%) had a presentation that could not be determined from the medical record (Table). Of the 17 painful lesions, 3 (17.6%) were found after a trauma brought attention to the site, and the other 14 (82.4%) were atraumatic in origin. 

Of the 10 patients with cortical breakthrough, 8 (80%) had painful lesions, 1 (10%) had a lesion that was found on screening examination, and 1 (10%) had a medical record insufficient for establishing clinical presentation. Of the 8 patients who underwent surgical stabilization, 6 (75%) had painful lesions. Only 1 patient with an asymptomatic tibia lesion underwent surgical intervention (total knee arthroplasty).

Surgical Intervention

Two patients (5.6%) with affected tibiae (4.8%) had pathologic fractures. One fracture (non-small cell lung cancer) was treated with open reduction and internal fixation (periarticular locking plate with cement augmentation), and the other (urothelial cancer) was treated with IMN fixation.

Ten patients (27.8%) with affected tibiae (23.8%) had radiographs that showed cortical breakthrough (Table). Two of the 10 cases were managed nonoperatively, and the patients died before surgical stabilization could be attempted. Of the 8 surgically managed cases, 3 were prophylactically stabilized with IMN (2 of these were augmented with cement, and the third with a screw-plate construct), 2 were treated with periarticular resection and reconstruction (total knee megaprosthesis), 1 was treated with an approach undertaken to address a concomitant distal femoral pathologic fracture, and 1 was treated with total knee arthroplasty undertaken to address lesions at the proximal end of the tibia and the distal end of the femur. 

Discussion

We have described a retrospective descriptive study conducted to characterize tibial metastases, their histologies, and the circumstances surrounding diagnosis and surgical management. In all cases, general findings confirmed advanced metastatic disease. In only 3 cases, the tibia lesion was an isolated metastatic lesion.

Sex predilection of tibial metastases remains controversial. One study found males had up to twice as many hand and foot metastases as women,¹¹ but this contrasts with the relatively equal sex ratio found in other studies^8,10 and in the present study. We found metastatic disease of the tibia was unsurprisingly concentrated in patients over age 40 years, in whom the vast majority of all cancers develop.^12,13 Our study agrees with those that have found most tibia lesions develop in patients in the 6th decade of life on average.^8,10 Mean age was 8.3 years higher in our male patients than in our female patients. 

Tumor Characteristics 

The most common primary neoplasms in our cohort were prostate, breast, and lung cancers, which are among the most common cancers in the United States^12,13 and which have a predilection for osseous spread.^2,6,9,14 Renal cell carcinoma has been reported to spread to distal (or “acral”) skeletal sites,^2-4,9,11,14 but the present study did not identify any patients with this diagnosis. Of our patients with a primary lung cancer for whom a histologic description was available (5/7), all had non-small cell lung cancer. Three patients had a primary malignancy of colorectal cancer, which occasionally metastasizes to the distal skeleton.^3,8,11 We identified 3 patients with diffuse large B-cell lymphoma, a histology not widely reported to metastasize to distal skeletal sites.

Metastatic disease of the tibia is most common at the proximal end of the bone.^1,10,11,14 Other studies^8,10 have found the proximal tibia is affected much more commonly than the tibial diaphysis, and even fewer cases develop at the distal end. Our findings agree with theirs: Proximal lesions outnumber all other lesions combined (Table).

Time to Metastasis

Distal metastases are typical of late-stage metastatic disease,^1,3 but quantification of the time from diagnosis of malignancy to presentation of a tibia lesion is not well defined. In our study, time to metastasis was <100 days for some patients (Table). As osseous involvement, especially acral disease, was considered a late-stage manifestation of malignancy, this result was unexpected and most likely represents undiagnosed and untreated malignancy. Six patients in this group were diagnosed with tibial metastases within 30 days, essentially at the same time the primary neoplasm was diagnosed. These findings suggest that a tibia lesion found at time of patient presentation should raise concern for late-stage undiagnosed metastatic cancer.

Other Osseous Disease

The patients identified in this study had advanced malignancy, and most had widespread bony dissemination. Those with the lowest disease burden had isolated tibia lesions or additional metastases only distal to the tibia lesion in the ipsilateral lower extremity. Most of these patients had undergone surgery or were scheduled for it (Table). Most of the patients with appendicular metastases proximal to the tibia lesion had disease of the femora, the most common long bones affected by osseous metastatic disease.^5,6 In accordance with orthopedic oncology principles, all other osseous disease should be thoroughly identified and staged before any surgical planning for identified tibia lesions. Ipsilateral distal femoral lesions are of particular importance for patients with proximal tibia lesions, as reconstruction with total knee endoprosthesis can potentially provide a functional reconstructive option after resection of both lesions. 

Clinical Presentation

Most of the patients who had cortical breakthrough or required surgical stabilization had painful lesions. Although tibial metastasis is rare, its potential occurrence should raise concerns and be investigated in the patient with tibial pain.

Surgical Intervention

General surgical management of metastatic disease of other long bones has been extensively studied,^6,7,9,14 but there are fewer published recommendations regarding specific treatments for metastatic lesions of the tibia. In 2003, Kelly and colleagues8 described an algorithm based on the anatomical location of the lesion, with either internal fixation or IMN fixation representing the preferred management for lesions in the metaphyseal or diaphyseal regions. For epiphyseal or extensive proximal metaphyseal lesions, modular oncology endoprostheses are described as the procedure of choice. Piccioli and colleagues¹⁰ in 2013 and Beauchamp and Sim¹ in 1988 described a similar operative approach.

It is unknown if the algorithm of Kelly and colleagues⁸ was referenced during clinical decision-making, but it appears operative management mirrored these principles. Deviations from this general approach in the operative management of the patients in the present study included modifications such as the addition of a screw-plate construct to an IMN for better stability.

Surgical management depends largely on the anatomical location within the bone and on remaining bone stock. Generally, extensive proximal disease is managed with total knee endoprosthesis reconstruction, diaphyseal disease with IMN, and distal disease with internal fixation. Construct augmentation, such as the addition of cement or use of additional hardware, is decided case by case on the basis of desired stability and surrounding bone stock.

Study Limitations

Despite being a larger series, this single-institution study had a relatively small sample size, and its patient demographics and primary malignancies may reflect institutional recruitment bias. In addition, the study was limited by its retrospective design and some incomplete medical records. Eleven patients had only a bone or positron emission tomography scan depicting metastatic disease, limiting characterization of these lesions. One patient lacked radiologic images, and characterizations were based on written reports. As multiple physicians were involved in diagnosis and treatment, there were many inconsistencies in clinical decision-making across the group.

Conclusion

Metastasis to the tibia is a rare but significant event in a subset of patients over the course of their treatment and surveillance. Patients may present with pain secondary to either pathologic or impending pathologic fractures, and in such instances surgical intervention is often needed. Despite the historical reports of “acral” histologies, tibia lesions are not indicative of histology, and biopsy should be considered, especially if management will depend on histology. Patients with lower leg pain and known malignancy should be evaluated to rule out tibial metastasis, but screening examinations may be prudent for asymptomatic patients as well. Increased vigilance may be indicated for those with prostate, breast, or lung cancer. These lesions should be surgically managed case by case using fundamental tenets of both orthopedic fracture care and orthopedic oncology. Ideally, patients should be treated by a multidisciplinary team using a patient-centered approach.

Take-Home Points

• Metastatic disease of the tibia is a rare but significant event in a subset of patients.
• Cancer histologies with historically “acral” spread may not apply to tibial disease.
• Patients with leg pain and any cancer diagnosis should be worked up for tibial metastases.
• Tibial disease is probably a late manifestation, and early detection may indicate late diagnosis of malignancy.
• The ultimate surgical plan for these patients should be a patient-centered multidisciplinary decision making process.

Metastatic dissemination to bones is common in advanced cancer stages and affects the axial and appendicular skeleton.^1-4 The appendicular skeleton bones most often involved are the proximal femur and the proximal humerus.^5,6 The tibia is involved third most often but is comparatively rarely affected.^4-6 Metastatic involvement distal to the knee or elbow is more typical of advanced disease.^1,3 Distal appendicular lesions are called acral metastases, but the term is inconsistently used and may refer to lesions either distal to the knee and elbow or distal to the ankle and wrist. Regardless of terminology, tibia lesions are uncommon and not well described.^1,4,7,8

The tibia is the primary weight-bearing leg bone. Metastatic tibia lesions may cause pain and instability and impair mobility. Although distal skeletal dissemination often presents late in advanced disease in patients with relatively poor prognoses, in some cases early surgical intervention is indicated for pain relief, increased mobility, and improved quality of life.^4,8-10

Materials and Methods

Our Institutional Review Board approved this single-institution retrospective study. We used proprietary research software (Clinical Looking Glass) to identify eligible patients treated between 2000 and 2013. The software was used to search all radiology and pathology reports for the term tibia or any variation (eg, tibial) and metastasis or any variation (eg, metastatic). The software was then used to search by Current Procedural Terminology code for any patients treated with intramedullary nail (IMN) or another tibial fixation method. This list was cross-referenced with the list of patients originally identified to help ensure that all eligible patients were identified. 

Inclusion criteria were known malignancy and imaging or biopsy evidence of a metastatic tibia lesion. Treatment strategies for patients with metastatic disease and patients with multiple myeloma are sometimes considered together because of similar goals and methodologies. We specifically excluded patients with multiple myeloma in order to more accurately characterize the natural history of metastatic disease and the timing of metastatic development and to report on a more homogeneous population. Patients were excluded if their electronic medical records were inadequate in establishing a diagnosis.

Demographic and pathology data were collected directly from the institutional electronic medical records system. Dr. Geller and Dr. Greenbaum used Centricity software (General Electric Healthcare) to review all imaging on medical diagnostic display monitors. If their interpretation differed from that in the radiology report, or if clarification was needed, the study was sent to Dr. Thornhill, the institution’s director of musculoskeletal radiology, for review and interpretation. Investigated radiographic characteristics included location, cortical breakthrough, presence of fracture, and size (if advanced imaging was available). Surgical interventions were recorded from reviews of operative reports and postoperative imaging studies.

Time to metastasis was defined as number of days from diagnosis of malignancy to diagnosis of tibial osseous spread. Date of diagnosis of malignancy was the date that a biopsy or other confirmatory test was performed. In cases in which that date was unavailable, an imaging study consistent with disease or a clinical note documenting the known diagnosis date was used instead. When only month and year (ie, not an exact date) of diagnosis were available, the 15th of the month was used as an estimate. Of the 36 patients, 4 had records insufficient for establishing date of diagnosis. The first date of any imaging study confirming (or suggestive of) a metastatic lesion of the tibia was used as the date of tibial metastasis. 

Many patients had osseous lesions at sites other than the tibiae. These lesions were noted on review of imaging studies, screening examinations, and physicians’ clinical notes. Widespread disease was defined as including both axial and appendicular lesions, and lesions of the tibiae.

Tibia lesion presentation was recorded as either symptomatic or incidental. If the tibiae were imaged for pain, including posttraumatic pain, the presentation was symptomatic. If a lesion was identified on staging examination (eg, bone or positron emission tomography scan), or if the tibiae were imaged for another reason, the presentation was incidental.

Results

Demographics

Thirty-six patients had 43 affected tibiae. Sixteen male patients (44.4% of the total) had 19 (44.2%) of the affected tibiae, and 20 female patients (55.6%) had the other 24 affected tibiae (55.8%). Mean age was 63.5 years for all patients (range, 6-95 years), 68.1 years for males, and 59.8 years for females. Of the 36 patients, 32 (88.9%) were over age 40 years (Table). All patients had radiographic evidence of ≥1 tibia lesion, and 6 (16.7%) also had biopsy-proven metastatic disease of the tibia.

Tumor Characteristics

There were 12 different primary neoplasms (Table). The most common were prostate cancer (7 patients, 19.4%; 10 tibiae, 23.3%), breast cancer (7 patients, 19.4%; 9 tibiae, 20.9%), and lung cancer (7 patients, 19.4%; 7 tibiae, 16.3%). For males, the most common diagnoses were prostate cancer (7 cases, 43.8% of males) and diffuse large B-cell lymphoma and lung cancer (3 cases and 18.8% of males each). For females, the most common diagnoses were breast cancer (7 cases, 35.0% of females) and lung cancer (4 cases, 20.0% of females). 

Most of the lesions were proximal (31 tibiae, 72.1%), followed by diaphyseal (7, 16.3%) and distal (2, 4.7%) (Table). Three tibiae (7.0%) were entirely involved, but 1 of these was more affected at the distal end. One tibia had 2 lesions, 1 proximal and 1 distal.

Time to Metastasis, Other Osseous Disease

Mean time from diagnosis of malignancy to diagnosis of osseous disease of the tibia was 1282 days (range, 0-3708 days) (Table). Of the 36 patients, 32 (88.9%) had other metastatic lesions, 3 (8.3%) had isolated tibia lesions, and 1 (2.8%) had a medical record insufficient for establishing lesion status (isolated or not). Of the 32 patients with known other osseous metastases, 14 (43.8%) had widespread (axial and additional appendicular) disease, and 3 (9.4%) had additional lesions only distal to the identified tibial metastases.

Clinical Presentation

Of the 36 lesions, 18 (50%) were asymptomatic and were found on screening examinations, 17 (47.2%) presented with pain, and 1 (2.8%) had a presentation that could not be determined from the medical record (Table). Of the 17 painful lesions, 3 (17.6%) were found after a trauma brought attention to the site, and the other 14 (82.4%) were atraumatic in origin. 

Of the 10 patients with cortical breakthrough, 8 (80%) had painful lesions, 1 (10%) had a lesion that was found on screening examination, and 1 (10%) had a medical record insufficient for establishing clinical presentation. Of the 8 patients who underwent surgical stabilization, 6 (75%) had painful lesions. Only 1 patient with an asymptomatic tibia lesion underwent surgical intervention (total knee arthroplasty).

Surgical Intervention

Two patients (5.6%) with affected tibiae (4.8%) had pathologic fractures. One fracture (non-small cell lung cancer) was treated with open reduction and internal fixation (periarticular locking plate with cement augmentation), and the other (urothelial cancer) was treated with IMN fixation.

Ten patients (27.8%) with affected tibiae (23.8%) had radiographs that showed cortical breakthrough (Table). Two of the 10 cases were managed nonoperatively, and the patients died before surgical stabilization could be attempted. Of the 8 surgically managed cases, 3 were prophylactically stabilized with IMN (2 of these were augmented with cement, and the third with a screw-plate construct), 2 were treated with periarticular resection and reconstruction (total knee megaprosthesis), 1 was treated with an approach undertaken to address a concomitant distal femoral pathologic fracture, and 1 was treated with total knee arthroplasty undertaken to address lesions at the proximal end of the tibia and the distal end of the femur. 

Discussion

We have described a retrospective descriptive study conducted to characterize tibial metastases, their histologies, and the circumstances surrounding diagnosis and surgical management. In all cases, general findings confirmed advanced metastatic disease. In only 3 cases, the tibia lesion was an isolated metastatic lesion.

Sex predilection of tibial metastases remains controversial. One study found males had up to twice as many hand and foot metastases as women,¹¹ but this contrasts with the relatively equal sex ratio found in other studies^8,10 and in the present study. We found metastatic disease of the tibia was unsurprisingly concentrated in patients over age 40 years, in whom the vast majority of all cancers develop.^12,13 Our study agrees with those that have found most tibia lesions develop in patients in the 6th decade of life on average.^8,10 Mean age was 8.3 years higher in our male patients than in our female patients. 

Tumor Characteristics 

The most common primary neoplasms in our cohort were prostate, breast, and lung cancers, which are among the most common cancers in the United States^12,13 and which have a predilection for osseous spread.^2,6,9,14 Renal cell carcinoma has been reported to spread to distal (or “acral”) skeletal sites,^2-4,9,11,14 but the present study did not identify any patients with this diagnosis. Of our patients with a primary lung cancer for whom a histologic description was available (5/7), all had non-small cell lung cancer. Three patients had a primary malignancy of colorectal cancer, which occasionally metastasizes to the distal skeleton.^3,8,11 We identified 3 patients with diffuse large B-cell lymphoma, a histology not widely reported to metastasize to distal skeletal sites.

Metastatic disease of the tibia is most common at the proximal end of the bone.^1,10,11,14 Other studies^8,10 have found the proximal tibia is affected much more commonly than the tibial diaphysis, and even fewer cases develop at the distal end. Our findings agree with theirs: Proximal lesions outnumber all other lesions combined (Table).

Time to Metastasis

Distal metastases are typical of late-stage metastatic disease,^1,3 but quantification of the time from diagnosis of malignancy to presentation of a tibia lesion is not well defined. In our study, time to metastasis was <100 days for some patients (Table). As osseous involvement, especially acral disease, was considered a late-stage manifestation of malignancy, this result was unexpected and most likely represents undiagnosed and untreated malignancy. Six patients in this group were diagnosed with tibial metastases within 30 days, essentially at the same time the primary neoplasm was diagnosed. These findings suggest that a tibia lesion found at time of patient presentation should raise concern for late-stage undiagnosed metastatic cancer.

Other Osseous Disease

The patients identified in this study had advanced malignancy, and most had widespread bony dissemination. Those with the lowest disease burden had isolated tibia lesions or additional metastases only distal to the tibia lesion in the ipsilateral lower extremity. Most of these patients had undergone surgery or were scheduled for it (Table). Most of the patients with appendicular metastases proximal to the tibia lesion had disease of the femora, the most common long bones affected by osseous metastatic disease.^5,6 In accordance with orthopedic oncology principles, all other osseous disease should be thoroughly identified and staged before any surgical planning for identified tibia lesions. Ipsilateral distal femoral lesions are of particular importance for patients with proximal tibia lesions, as reconstruction with total knee endoprosthesis can potentially provide a functional reconstructive option after resection of both lesions. 

Clinical Presentation

Most of the patients who had cortical breakthrough or required surgical stabilization had painful lesions. Although tibial metastasis is rare, its potential occurrence should raise concerns and be investigated in the patient with tibial pain.

Surgical Intervention

General surgical management of metastatic disease of other long bones has been extensively studied,^6,7,9,14 but there are fewer published recommendations regarding specific treatments for metastatic lesions of the tibia. In 2003, Kelly and colleagues8 described an algorithm based on the anatomical location of the lesion, with either internal fixation or IMN fixation representing the preferred management for lesions in the metaphyseal or diaphyseal regions. For epiphyseal or extensive proximal metaphyseal lesions, modular oncology endoprostheses are described as the procedure of choice. Piccioli and colleagues¹⁰ in 2013 and Beauchamp and Sim¹ in 1988 described a similar operative approach.

It is unknown if the algorithm of Kelly and colleagues⁸ was referenced during clinical decision-making, but it appears operative management mirrored these principles. Deviations from this general approach in the operative management of the patients in the present study included modifications such as the addition of a screw-plate construct to an IMN for better stability.

Surgical management depends largely on the anatomical location within the bone and on remaining bone stock. Generally, extensive proximal disease is managed with total knee endoprosthesis reconstruction, diaphyseal disease with IMN, and distal disease with internal fixation. Construct augmentation, such as the addition of cement or use of additional hardware, is decided case by case on the basis of desired stability and surrounding bone stock.

Study Limitations

Despite being a larger series, this single-institution study had a relatively small sample size, and its patient demographics and primary malignancies may reflect institutional recruitment bias. In addition, the study was limited by its retrospective design and some incomplete medical records. Eleven patients had only a bone or positron emission tomography scan depicting metastatic disease, limiting characterization of these lesions. One patient lacked radiologic images, and characterizations were based on written reports. As multiple physicians were involved in diagnosis and treatment, there were many inconsistencies in clinical decision-making across the group.

Conclusion

Metastasis to the tibia is a rare but significant event in a subset of patients over the course of their treatment and surveillance. Patients may present with pain secondary to either pathologic or impending pathologic fractures, and in such instances surgical intervention is often needed. Despite the historical reports of “acral” histologies, tibia lesions are not indicative of histology, and biopsy should be considered, especially if management will depend on histology. Patients with lower leg pain and known malignancy should be evaluated to rule out tibial metastasis, but screening examinations may be prudent for asymptomatic patients as well. Increased vigilance may be indicated for those with prostate, breast, or lung cancer. These lesions should be surgically managed case by case using fundamental tenets of both orthopedic fracture care and orthopedic oncology. Ideally, patients should be treated by a multidisciplinary team using a patient-centered approach.

Take-Home Points

• Metastatic disease of the tibia is a rare but significant event in a subset of patients.
• Cancer histologies with historically “acral” spread may not apply to tibial disease.
• Patients with leg pain and any cancer diagnosis should be worked up for tibial metastases.
• Tibial disease is probably a late manifestation, and early detection may indicate late diagnosis of malignancy.
• The ultimate surgical plan for these patients should be a patient-centered multidisciplinary decision making process.

Metastatic dissemination to bones is common in advanced cancer stages and affects the axial and appendicular skeleton.^1-4 The appendicular skeleton bones most often involved are the proximal femur and the proximal humerus.^5,6 The tibia is involved third most often but is comparatively rarely affected.^4-6 Metastatic involvement distal to the knee or elbow is more typical of advanced disease.^1,3 Distal appendicular lesions are called acral metastases, but the term is inconsistently used and may refer to lesions either distal to the knee and elbow or distal to the ankle and wrist. Regardless of terminology, tibia lesions are uncommon and not well described.^1,4,7,8

The tibia is the primary weight-bearing leg bone. Metastatic tibia lesions may cause pain and instability and impair mobility. Although distal skeletal dissemination often presents late in advanced disease in patients with relatively poor prognoses, in some cases early surgical intervention is indicated for pain relief, increased mobility, and improved quality of life.^4,8-10

Materials and Methods

Our Institutional Review Board approved this single-institution retrospective study. We used proprietary research software (Clinical Looking Glass) to identify eligible patients treated between 2000 and 2013. The software was used to search all radiology and pathology reports for the term tibia or any variation (eg, tibial) and metastasis or any variation (eg, metastatic). The software was then used to search by Current Procedural Terminology code for any patients treated with intramedullary nail (IMN) or another tibial fixation method. This list was cross-referenced with the list of patients originally identified to help ensure that all eligible patients were identified. 

Inclusion criteria were known malignancy and imaging or biopsy evidence of a metastatic tibia lesion. Treatment strategies for patients with metastatic disease and patients with multiple myeloma are sometimes considered together because of similar goals and methodologies. We specifically excluded patients with multiple myeloma in order to more accurately characterize the natural history of metastatic disease and the timing of metastatic development and to report on a more homogeneous population. Patients were excluded if their electronic medical records were inadequate in establishing a diagnosis.

Demographic and pathology data were collected directly from the institutional electronic medical records system. Dr. Geller and Dr. Greenbaum used Centricity software (General Electric Healthcare) to review all imaging on medical diagnostic display monitors. If their interpretation differed from that in the radiology report, or if clarification was needed, the study was sent to Dr. Thornhill, the institution’s director of musculoskeletal radiology, for review and interpretation. Investigated radiographic characteristics included location, cortical breakthrough, presence of fracture, and size (if advanced imaging was available). Surgical interventions were recorded from reviews of operative reports and postoperative imaging studies.

Time to metastasis was defined as number of days from diagnosis of malignancy to diagnosis of tibial osseous spread. Date of diagnosis of malignancy was the date that a biopsy or other confirmatory test was performed. In cases in which that date was unavailable, an imaging study consistent with disease or a clinical note documenting the known diagnosis date was used instead. When only month and year (ie, not an exact date) of diagnosis were available, the 15th of the month was used as an estimate. Of the 36 patients, 4 had records insufficient for establishing date of diagnosis. The first date of any imaging study confirming (or suggestive of) a metastatic lesion of the tibia was used as the date of tibial metastasis. 

Many patients had osseous lesions at sites other than the tibiae. These lesions were noted on review of imaging studies, screening examinations, and physicians’ clinical notes. Widespread disease was defined as including both axial and appendicular lesions, and lesions of the tibiae.

Tibia lesion presentation was recorded as either symptomatic or incidental. If the tibiae were imaged for pain, including posttraumatic pain, the presentation was symptomatic. If a lesion was identified on staging examination (eg, bone or positron emission tomography scan), or if the tibiae were imaged for another reason, the presentation was incidental.

Results

Demographics

Thirty-six patients had 43 affected tibiae. Sixteen male patients (44.4% of the total) had 19 (44.2%) of the affected tibiae, and 20 female patients (55.6%) had the other 24 affected tibiae (55.8%). Mean age was 63.5 years for all patients (range, 6-95 years), 68.1 years for males, and 59.8 years for females. Of the 36 patients, 32 (88.9%) were over age 40 years (Table). All patients had radiographic evidence of ≥1 tibia lesion, and 6 (16.7%) also had biopsy-proven metastatic disease of the tibia.

Tumor Characteristics

There were 12 different primary neoplasms (Table). The most common were prostate cancer (7 patients, 19.4%; 10 tibiae, 23.3%), breast cancer (7 patients, 19.4%; 9 tibiae, 20.9%), and lung cancer (7 patients, 19.4%; 7 tibiae, 16.3%). For males, the most common diagnoses were prostate cancer (7 cases, 43.8% of males) and diffuse large B-cell lymphoma and lung cancer (3 cases and 18.8% of males each). For females, the most common diagnoses were breast cancer (7 cases, 35.0% of females) and lung cancer (4 cases, 20.0% of females). 

Most of the lesions were proximal (31 tibiae, 72.1%), followed by diaphyseal (7, 16.3%) and distal (2, 4.7%) (Table). Three tibiae (7.0%) were entirely involved, but 1 of these was more affected at the distal end. One tibia had 2 lesions, 1 proximal and 1 distal.

Time to Metastasis, Other Osseous Disease

Mean time from diagnosis of malignancy to diagnosis of osseous disease of the tibia was 1282 days (range, 0-3708 days) (Table). Of the 36 patients, 32 (88.9%) had other metastatic lesions, 3 (8.3%) had isolated tibia lesions, and 1 (2.8%) had a medical record insufficient for establishing lesion status (isolated or not). Of the 32 patients with known other osseous metastases, 14 (43.8%) had widespread (axial and additional appendicular) disease, and 3 (9.4%) had additional lesions only distal to the identified tibial metastases.

Clinical Presentation

Of the 36 lesions, 18 (50%) were asymptomatic and were found on screening examinations, 17 (47.2%) presented with pain, and 1 (2.8%) had a presentation that could not be determined from the medical record (Table). Of the 17 painful lesions, 3 (17.6%) were found after a trauma brought attention to the site, and the other 14 (82.4%) were atraumatic in origin. 

Of the 10 patients with cortical breakthrough, 8 (80%) had painful lesions, 1 (10%) had a lesion that was found on screening examination, and 1 (10%) had a medical record insufficient for establishing clinical presentation. Of the 8 patients who underwent surgical stabilization, 6 (75%) had painful lesions. Only 1 patient with an asymptomatic tibia lesion underwent surgical intervention (total knee arthroplasty).

Surgical Intervention

Two patients (5.6%) with affected tibiae (4.8%) had pathologic fractures. One fracture (non-small cell lung cancer) was treated with open reduction and internal fixation (periarticular locking plate with cement augmentation), and the other (urothelial cancer) was treated with IMN fixation.

Ten patients (27.8%) with affected tibiae (23.8%) had radiographs that showed cortical breakthrough (Table). Two of the 10 cases were managed nonoperatively, and the patients died before surgical stabilization could be attempted. Of the 8 surgically managed cases, 3 were prophylactically stabilized with IMN (2 of these were augmented with cement, and the third with a screw-plate construct), 2 were treated with periarticular resection and reconstruction (total knee megaprosthesis), 1 was treated with an approach undertaken to address a concomitant distal femoral pathologic fracture, and 1 was treated with total knee arthroplasty undertaken to address lesions at the proximal end of the tibia and the distal end of the femur. 

Discussion

We have described a retrospective descriptive study conducted to characterize tibial metastases, their histologies, and the circumstances surrounding diagnosis and surgical management. In all cases, general findings confirmed advanced metastatic disease. In only 3 cases, the tibia lesion was an isolated metastatic lesion.

Sex predilection of tibial metastases remains controversial. One study found males had up to twice as many hand and foot metastases as women,¹¹ but this contrasts with the relatively equal sex ratio found in other studies^8,10 and in the present study. We found metastatic disease of the tibia was unsurprisingly concentrated in patients over age 40 years, in whom the vast majority of all cancers develop.^12,13 Our study agrees with those that have found most tibia lesions develop in patients in the 6th decade of life on average.^8,10 Mean age was 8.3 years higher in our male patients than in our female patients. 

Tumor Characteristics 

The most common primary neoplasms in our cohort were prostate, breast, and lung cancers, which are among the most common cancers in the United States^12,13 and which have a predilection for osseous spread.^2,6,9,14 Renal cell carcinoma has been reported to spread to distal (or “acral”) skeletal sites,^2-4,9,11,14 but the present study did not identify any patients with this diagnosis. Of our patients with a primary lung cancer for whom a histologic description was available (5/7), all had non-small cell lung cancer. Three patients had a primary malignancy of colorectal cancer, which occasionally metastasizes to the distal skeleton.^3,8,11 We identified 3 patients with diffuse large B-cell lymphoma, a histology not widely reported to metastasize to distal skeletal sites.

Metastatic disease of the tibia is most common at the proximal end of the bone.^1,10,11,14 Other studies^8,10 have found the proximal tibia is affected much more commonly than the tibial diaphysis, and even fewer cases develop at the distal end. Our findings agree with theirs: Proximal lesions outnumber all other lesions combined (Table).

Time to Metastasis

Distal metastases are typical of late-stage metastatic disease,^1,3 but quantification of the time from diagnosis of malignancy to presentation of a tibia lesion is not well defined. In our study, time to metastasis was <100 days for some patients (Table). As osseous involvement, especially acral disease, was considered a late-stage manifestation of malignancy, this result was unexpected and most likely represents undiagnosed and untreated malignancy. Six patients in this group were diagnosed with tibial metastases within 30 days, essentially at the same time the primary neoplasm was diagnosed. These findings suggest that a tibia lesion found at time of patient presentation should raise concern for late-stage undiagnosed metastatic cancer.

Other Osseous Disease

The patients identified in this study had advanced malignancy, and most had widespread bony dissemination. Those with the lowest disease burden had isolated tibia lesions or additional metastases only distal to the tibia lesion in the ipsilateral lower extremity. Most of these patients had undergone surgery or were scheduled for it (Table). Most of the patients with appendicular metastases proximal to the tibia lesion had disease of the femora, the most common long bones affected by osseous metastatic disease.^5,6 In accordance with orthopedic oncology principles, all other osseous disease should be thoroughly identified and staged before any surgical planning for identified tibia lesions. Ipsilateral distal femoral lesions are of particular importance for patients with proximal tibia lesions, as reconstruction with total knee endoprosthesis can potentially provide a functional reconstructive option after resection of both lesions. 

Clinical Presentation

Most of the patients who had cortical breakthrough or required surgical stabilization had painful lesions. Although tibial metastasis is rare, its potential occurrence should raise concerns and be investigated in the patient with tibial pain.

Surgical Intervention

General surgical management of metastatic disease of other long bones has been extensively studied,^6,7,9,14 but there are fewer published recommendations regarding specific treatments for metastatic lesions of the tibia. In 2003, Kelly and colleagues8 described an algorithm based on the anatomical location of the lesion, with either internal fixation or IMN fixation representing the preferred management for lesions in the metaphyseal or diaphyseal regions. For epiphyseal or extensive proximal metaphyseal lesions, modular oncology endoprostheses are described as the procedure of choice. Piccioli and colleagues¹⁰ in 2013 and Beauchamp and Sim¹ in 1988 described a similar operative approach.

It is unknown if the algorithm of Kelly and colleagues⁸ was referenced during clinical decision-making, but it appears operative management mirrored these principles. Deviations from this general approach in the operative management of the patients in the present study included modifications such as the addition of a screw-plate construct to an IMN for better stability.

Surgical management depends largely on the anatomical location within the bone and on remaining bone stock. Generally, extensive proximal disease is managed with total knee endoprosthesis reconstruction, diaphyseal disease with IMN, and distal disease with internal fixation. Construct augmentation, such as the addition of cement or use of additional hardware, is decided case by case on the basis of desired stability and surrounding bone stock.

Study Limitations

Despite being a larger series, this single-institution study had a relatively small sample size, and its patient demographics and primary malignancies may reflect institutional recruitment bias. In addition, the study was limited by its retrospective design and some incomplete medical records. Eleven patients had only a bone or positron emission tomography scan depicting metastatic disease, limiting characterization of these lesions. One patient lacked radiologic images, and characterizations were based on written reports. As multiple physicians were involved in diagnosis and treatment, there were many inconsistencies in clinical decision-making across the group.

Conclusion

Metastasis to the tibia is a rare but significant event in a subset of patients over the course of their treatment and surveillance. Patients may present with pain secondary to either pathologic or impending pathologic fractures, and in such instances surgical intervention is often needed. Despite the historical reports of “acral” histologies, tibia lesions are not indicative of histology, and biopsy should be considered, especially if management will depend on histology. Patients with lower leg pain and known malignancy should be evaluated to rule out tibial metastasis, but screening examinations may be prudent for asymptomatic patients as well. Increased vigilance may be indicated for those with prostate, breast, or lung cancer. These lesions should be surgically managed case by case using fundamental tenets of both orthopedic fracture care and orthopedic oncology. Ideally, patients should be treated by a multidisciplinary team using a patient-centered approach.

ATLANTA – The past year brought a flurry of new drug approvals for the treatment of acute myeloid leukemia (AML), including CPX-351, midostaurin, gemtuzumab ozogamicin, and enasidenib.

During a special interest session at the annual meeting of the American Society of Hematology, Food and Drug Administration representatives discussed the available data and approval process for these drugs, and clinicians discussed their use in the real-world setting.

In this video interview, Laura C. Michaelis, MD, discusses clinical considerations regarding the use of CPX-351 (Vyxeos) – a liposome-encapsulated combination of daunorubicin and cytarabine approved in August for patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes, and midostaurin (Rydapt), which was approved in April for the treatment of newly diagnosed AML patients who are FLT3 mutation-positive. She also discussed future directions for these agents.

“So what clinicians are faced with is, all of a sudden, a number of new agents, and no particularly vetted or data-based algorithm by which to assign patients from one to the other,” said Dr. Michaelis, of the Medical College of Wisconsin, Milwaukee, adding that none of the drugs have been compared against one another.

In her own practice, when it comes to CPX-351, she said she first discusses the pros and cons with patients.

“This drug is used for older individuals ... with very adverse risk disease, and so the first question is do you fit the trial entry criteria, do you want to go through induction, do you understand what that’s going to mean, and am I going to take you to transplant after we go through this.”

As for midostaurin, she said she tries to use it on anyone who fits the trial criteria and is FLT-3 positive.

“The trick with that is that we don’t know the FLT-3 status at the time we have to start induction, so it’s hard to determine the exact right doses of your induction regimen knowing that you’re not going to get the test back until day 6, 7, 8, and you’re supposed to start delivering the drug on day 8, so we still have a ways as a care community to catch up with being able to give these drugs in a manner that was the same as what was delivered in the trials that led to approval.”

She also discussed the potential for combining treatments.

“I think there’s really room for studies on combinations of inhibitors plus the CPX, the safety of using a variety of induction regimens alongside midostaurin, and safety of combining things, like with midostaurin for example, with some of our antifungals ... and to make sure that that’s safe. So yeah, we’ve got a lot more to do,” she said.

Dr. Michaelis serves on an advisory board for Novartis.

[email protected]

ATLANTA – The past year brought a flurry of new drug approvals for the treatment of acute myeloid leukemia (AML), including CPX-351, midostaurin, gemtuzumab ozogamicin, and enasidenib.

During a special interest session at the annual meeting of the American Society of Hematology, Food and Drug Administration representatives discussed the available data and approval process for these drugs, and clinicians discussed their use in the real-world setting.

In this video interview, Laura C. Michaelis, MD, discusses clinical considerations regarding the use of CPX-351 (Vyxeos) – a liposome-encapsulated combination of daunorubicin and cytarabine approved in August for patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes, and midostaurin (Rydapt), which was approved in April for the treatment of newly diagnosed AML patients who are FLT3 mutation-positive. She also discussed future directions for these agents.

“So what clinicians are faced with is, all of a sudden, a number of new agents, and no particularly vetted or data-based algorithm by which to assign patients from one to the other,” said Dr. Michaelis, of the Medical College of Wisconsin, Milwaukee, adding that none of the drugs have been compared against one another.

In her own practice, when it comes to CPX-351, she said she first discusses the pros and cons with patients.

“This drug is used for older individuals ... with very adverse risk disease, and so the first question is do you fit the trial entry criteria, do you want to go through induction, do you understand what that’s going to mean, and am I going to take you to transplant after we go through this.”

As for midostaurin, she said she tries to use it on anyone who fits the trial criteria and is FLT-3 positive.

“The trick with that is that we don’t know the FLT-3 status at the time we have to start induction, so it’s hard to determine the exact right doses of your induction regimen knowing that you’re not going to get the test back until day 6, 7, 8, and you’re supposed to start delivering the drug on day 8, so we still have a ways as a care community to catch up with being able to give these drugs in a manner that was the same as what was delivered in the trials that led to approval.”

She also discussed the potential for combining treatments.

“I think there’s really room for studies on combinations of inhibitors plus the CPX, the safety of using a variety of induction regimens alongside midostaurin, and safety of combining things, like with midostaurin for example, with some of our antifungals ... and to make sure that that’s safe. So yeah, we’ve got a lot more to do,” she said.

Dr. Michaelis serves on an advisory board for Novartis.

[email protected]

ATLANTA – The past year brought a flurry of new drug approvals for the treatment of acute myeloid leukemia (AML), including CPX-351, midostaurin, gemtuzumab ozogamicin, and enasidenib.

During a special interest session at the annual meeting of the American Society of Hematology, Food and Drug Administration representatives discussed the available data and approval process for these drugs, and clinicians discussed their use in the real-world setting.

In this video interview, Laura C. Michaelis, MD, discusses clinical considerations regarding the use of CPX-351 (Vyxeos) – a liposome-encapsulated combination of daunorubicin and cytarabine approved in August for patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes, and midostaurin (Rydapt), which was approved in April for the treatment of newly diagnosed AML patients who are FLT3 mutation-positive. She also discussed future directions for these agents.

“So what clinicians are faced with is, all of a sudden, a number of new agents, and no particularly vetted or data-based algorithm by which to assign patients from one to the other,” said Dr. Michaelis, of the Medical College of Wisconsin, Milwaukee, adding that none of the drugs have been compared against one another.

In her own practice, when it comes to CPX-351, she said she first discusses the pros and cons with patients.

“This drug is used for older individuals ... with very adverse risk disease, and so the first question is do you fit the trial entry criteria, do you want to go through induction, do you understand what that’s going to mean, and am I going to take you to transplant after we go through this.”

As for midostaurin, she said she tries to use it on anyone who fits the trial criteria and is FLT-3 positive.

“The trick with that is that we don’t know the FLT-3 status at the time we have to start induction, so it’s hard to determine the exact right doses of your induction regimen knowing that you’re not going to get the test back until day 6, 7, 8, and you’re supposed to start delivering the drug on day 8, so we still have a ways as a care community to catch up with being able to give these drugs in a manner that was the same as what was delivered in the trials that led to approval.”

She also discussed the potential for combining treatments.

“I think there’s really room for studies on combinations of inhibitors plus the CPX, the safety of using a variety of induction regimens alongside midostaurin, and safety of combining things, like with midostaurin for example, with some of our antifungals ... and to make sure that that’s safe. So yeah, we’ve got a lot more to do,” she said.

Dr. Michaelis serves on an advisory board for Novartis.

[email protected]

Question: Choose the best answer regarding physician-assisted suicide in the United States:

A. It is now legal in most states.

B. Under California law, assisting or causing one to commit suicide, including physician-assisted suicide, still remains a felony.

C. Both the U.S. Supreme Court and the New York Court of Appeals have held there is no constitutional right to physician-assisted suicide.

D. The American Medical Association is neutral on the issue.

E. Pain relief is the overriding reason for patients who request physician-assisted suicide.

Answer: C. We reviewed this topic in one of our regular columns in 2013.¹ At that time, efforts to legalize physician-assisted suicide (PAS) appeared to be gathering momentum across the country, with four jurisdictions having legalized the practice, beginning with Oregon in 1994. The other states were Washington, Vermont, and Montana, whose Supreme Court held that there was no public interest reason against the practice.²

Since that time, California, Colorado, and the District of Columbia have joined the group. Currently, PAS – but not euthanasia – is legally available in these jurisdictions and in Switzerland, but both can be legally practiced in Belgium, Canada, Colombia, Luxembourg, and the Netherlands.

All state statutes permitting PAS provide similar provisions and safeguards. Only competent individuals who are terminally ill, i.e., death expected within 6 months, can make a request for a lethal dose of medication to carry out the suicidal act. The request to the doctor is first made verbally, then in writing, and a second opinion must be obtained to confirm the patient’s intent, understanding, and free choice. There is also a waiting period.

Public support for euthanasia and PAS in the United States is said to have plateaued since the 1990s. But a significant number of Americans, 67%, still favor PAS, up from 56% a decade ago.³ However, not many patients resort to PAS – usually those with terminal cancers or neuromuscular conditions – and only a minority of physicians are participants.

For example, 61 physicians in Oregon wrote a total of 115 prescriptions in 2012; there were 77 known Death With Dignity Act deaths in Oregon that year.⁴ In Oregon and Washington State, less than 1% of licensed physicians write prescriptions for physician-assisted suicide each year. In contrast, about half or more of physicians in the Netherlands and Belgium reported ever having received a request, and 60% of Dutch physicians have granted such requests.

The California Department of Public Health reported that 111 terminally ill patients availed themselves of California’s End of Life Option Act in the 7 months after it became effective on June 9, 2016.

In a recent review on euthanasia and PAS for the period 1947-2016, Ezekiel Emanuel, MD, and colleagues noted that typical patients were older, white, and well educated, and pain was mostly not reported as the primary motivation.⁵ A large portion of patients receiving PAS in Oregon and Washington were enrolled in hospice or palliative care. Abuses have not been apparent.

In the vast majority of jurisdictions, assisting or causing one to commit suicide, including PAS, still remains a crime; for example, it is considered manslaughter under Hawaii state law §707-702.

In distinguishing between assisting suicide and withdrawing life-sustaining treatment, the U.S. Supreme Court’s landmark 1997 Vacco v. Quill decision emphasized issues of causation and intent.⁶ On causation, the court reasoned that when a patient refuses life-sustaining treatment, he dies from an underlying fatal disease; but if a patient ingests a lethal medication, he is killed by that medication. As to intent, a physician who honors a patient’s refusal of treatment purposefully intends only to respect his patient’s wishes and to cease doing futile or degrading things. On the other hand, a doctor who assists a suicide “must, necessarily and indubitably, intend primarily that the patient be made dead.”

In its companion case Washington v. Glucksberg, the Supreme Court held that the asserted “right” to assistance in committing suicide is not a fundamental liberty interest protected by the due process clause.⁷

State supreme courts in Florida, New Mexico, and elsewhere have likewise rebuffed claims of any constitutional right to PAS. The latest court to so rule is in New York, which has a long history of criminalizing assisted suicide.⁸ The New York Court of Appeals recently addressed claims brought by three terminally ill individuals, several medical providers, and a nonprofit entity seeking a declaration that New York’s “assisted suicide” statutes exclude physicians from prescribing a lethal dose of drugs to terminally ill, competent patients.

The court unequivocally rejected such claims and affirmed that a physician who assists a suicide by prescribing lethal doses of drugs is subject to criminal prosecution for second-degree manslaughter. It refused to regard PAS as being different from assisted suicide in general, and it rejected the constitutional claim to assisted suicide by a terminally ill person. The state appeals court reiterated the U.S. Supreme Court’s distinction between refusing life-sustaining treatment and assisted suicide, the former being “at least partially rooted in notions of bodily integrity, as the right to refuse treatment is a consequence of a person’s right to resist unwanted bodily invasions.” The New York Court of Appeals also noted that the state has a legitimate purpose and a rational basis for guarding against the risks of mistake and abuse.

These developments may signal a shift away from the legalization of PAS, as recently suggested in a Washington Post article.⁹ According to the end-of-life advocacy organization Compassion and Choices, none of the 27 states where such measures were introduced in 2017 passed them into law, including states such as Connecticut, Hawaii, and Rhode Island. In Central and Eastern Europe, support is decreasing, whereas the opposite is true in Western Europe.

U.S. federal lawmakers also appear to be pushing back. On July 13, 2017, the U.S. House Committee on Appropriations voted to block implementation of a “death with dignity” statute passed by the District of Columbia. Further, 11 House members – including 6 Democrats – have introduced a resolution asserting that PAS undermines a key safeguard that protects our nation’s most vulnerable citizens, including the elderly, people with disabilities, and people experiencing psychiatric diagnoses.¹⁰

The American Medical Association is steadfast in its opposition to PAS and euthanasia. In its latest Code of Ethics, the AMA reaffirmed its long-held position that “allowing physicians to engage in assisted suicide would cause more harm than good. Physician-assisted suicide is fundamentally incompatible with the physician’s role as healer, would be difficult or impossible to control, and would pose serious societal risks. … Instead of participating in assisted suicide, physicians must aggressively respond to the needs of patients at the end of life.”¹¹

References

1. “Physician-assisted suicide,” Internal Medicine News, Oct. 14, 2013.

2. Baxter v. State of Montana, 224 P. 3d 1211 (2010).

3. “Majority of Americans Remain Supportive of Euthanasia,” Gallup News, June 12, 2017.

4. Statistics available at public.health.oregon.gov under Oregon Death with Dignity Act.

5. JAMA. 2016 Jul 5;316(1):79-90.

6. Vacco v. Quill, 117 S. Ct. 2293 (1997).

7. Washington v. Glucksberg, 521 U.S. 702 (1997).

8. Myers v. Schneiderman, New York Court of Appeals, 2017.

9. “Legalizing assisted suicide has stalled at every level,” Washington Post, Oct. 24, 2017.

10. H. Con. Res. 80, 115th Congress (2017-2018).

11. AMA Code of Medical Ethics §5.7 (2017).

Question: Choose the best answer regarding physician-assisted suicide in the United States:

A. It is now legal in most states.

B. Under California law, assisting or causing one to commit suicide, including physician-assisted suicide, still remains a felony.

C. Both the U.S. Supreme Court and the New York Court of Appeals have held there is no constitutional right to physician-assisted suicide.

D. The American Medical Association is neutral on the issue.

E. Pain relief is the overriding reason for patients who request physician-assisted suicide.

Answer: C. We reviewed this topic in one of our regular columns in 2013.¹ At that time, efforts to legalize physician-assisted suicide (PAS) appeared to be gathering momentum across the country, with four jurisdictions having legalized the practice, beginning with Oregon in 1994. The other states were Washington, Vermont, and Montana, whose Supreme Court held that there was no public interest reason against the practice.²

Since that time, California, Colorado, and the District of Columbia have joined the group. Currently, PAS – but not euthanasia – is legally available in these jurisdictions and in Switzerland, but both can be legally practiced in Belgium, Canada, Colombia, Luxembourg, and the Netherlands.

All state statutes permitting PAS provide similar provisions and safeguards. Only competent individuals who are terminally ill, i.e., death expected within 6 months, can make a request for a lethal dose of medication to carry out the suicidal act. The request to the doctor is first made verbally, then in writing, and a second opinion must be obtained to confirm the patient’s intent, understanding, and free choice. There is also a waiting period.

Public support for euthanasia and PAS in the United States is said to have plateaued since the 1990s. But a significant number of Americans, 67%, still favor PAS, up from 56% a decade ago.³ However, not many patients resort to PAS – usually those with terminal cancers or neuromuscular conditions – and only a minority of physicians are participants.

For example, 61 physicians in Oregon wrote a total of 115 prescriptions in 2012; there were 77 known Death With Dignity Act deaths in Oregon that year.⁴ In Oregon and Washington State, less than 1% of licensed physicians write prescriptions for physician-assisted suicide each year. In contrast, about half or more of physicians in the Netherlands and Belgium reported ever having received a request, and 60% of Dutch physicians have granted such requests.

The California Department of Public Health reported that 111 terminally ill patients availed themselves of California’s End of Life Option Act in the 7 months after it became effective on June 9, 2016.

In a recent review on euthanasia and PAS for the period 1947-2016, Ezekiel Emanuel, MD, and colleagues noted that typical patients were older, white, and well educated, and pain was mostly not reported as the primary motivation.⁵ A large portion of patients receiving PAS in Oregon and Washington were enrolled in hospice or palliative care. Abuses have not been apparent.

In the vast majority of jurisdictions, assisting or causing one to commit suicide, including PAS, still remains a crime; for example, it is considered manslaughter under Hawaii state law §707-702.

In distinguishing between assisting suicide and withdrawing life-sustaining treatment, the U.S. Supreme Court’s landmark 1997 Vacco v. Quill decision emphasized issues of causation and intent.⁶ On causation, the court reasoned that when a patient refuses life-sustaining treatment, he dies from an underlying fatal disease; but if a patient ingests a lethal medication, he is killed by that medication. As to intent, a physician who honors a patient’s refusal of treatment purposefully intends only to respect his patient’s wishes and to cease doing futile or degrading things. On the other hand, a doctor who assists a suicide “must, necessarily and indubitably, intend primarily that the patient be made dead.”

In its companion case Washington v. Glucksberg, the Supreme Court held that the asserted “right” to assistance in committing suicide is not a fundamental liberty interest protected by the due process clause.⁷

State supreme courts in Florida, New Mexico, and elsewhere have likewise rebuffed claims of any constitutional right to PAS. The latest court to so rule is in New York, which has a long history of criminalizing assisted suicide.⁸ The New York Court of Appeals recently addressed claims brought by three terminally ill individuals, several medical providers, and a nonprofit entity seeking a declaration that New York’s “assisted suicide” statutes exclude physicians from prescribing a lethal dose of drugs to terminally ill, competent patients.

The court unequivocally rejected such claims and affirmed that a physician who assists a suicide by prescribing lethal doses of drugs is subject to criminal prosecution for second-degree manslaughter. It refused to regard PAS as being different from assisted suicide in general, and it rejected the constitutional claim to assisted suicide by a terminally ill person. The state appeals court reiterated the U.S. Supreme Court’s distinction between refusing life-sustaining treatment and assisted suicide, the former being “at least partially rooted in notions of bodily integrity, as the right to refuse treatment is a consequence of a person’s right to resist unwanted bodily invasions.” The New York Court of Appeals also noted that the state has a legitimate purpose and a rational basis for guarding against the risks of mistake and abuse.

These developments may signal a shift away from the legalization of PAS, as recently suggested in a Washington Post article.⁹ According to the end-of-life advocacy organization Compassion and Choices, none of the 27 states where such measures were introduced in 2017 passed them into law, including states such as Connecticut, Hawaii, and Rhode Island. In Central and Eastern Europe, support is decreasing, whereas the opposite is true in Western Europe.

U.S. federal lawmakers also appear to be pushing back. On July 13, 2017, the U.S. House Committee on Appropriations voted to block implementation of a “death with dignity” statute passed by the District of Columbia. Further, 11 House members – including 6 Democrats – have introduced a resolution asserting that PAS undermines a key safeguard that protects our nation’s most vulnerable citizens, including the elderly, people with disabilities, and people experiencing psychiatric diagnoses.¹⁰

The American Medical Association is steadfast in its opposition to PAS and euthanasia. In its latest Code of Ethics, the AMA reaffirmed its long-held position that “allowing physicians to engage in assisted suicide would cause more harm than good. Physician-assisted suicide is fundamentally incompatible with the physician’s role as healer, would be difficult or impossible to control, and would pose serious societal risks. … Instead of participating in assisted suicide, physicians must aggressively respond to the needs of patients at the end of life.”¹¹

References

1. “Physician-assisted suicide,” Internal Medicine News, Oct. 14, 2013.

2. Baxter v. State of Montana, 224 P. 3d 1211 (2010).

3. “Majority of Americans Remain Supportive of Euthanasia,” Gallup News, June 12, 2017.

4. Statistics available at public.health.oregon.gov under Oregon Death with Dignity Act.

5. JAMA. 2016 Jul 5;316(1):79-90.

6. Vacco v. Quill, 117 S. Ct. 2293 (1997).

7. Washington v. Glucksberg, 521 U.S. 702 (1997).

8. Myers v. Schneiderman, New York Court of Appeals, 2017.

9. “Legalizing assisted suicide has stalled at every level,” Washington Post, Oct. 24, 2017.

10. H. Con. Res. 80, 115th Congress (2017-2018).

11. AMA Code of Medical Ethics §5.7 (2017).

Question: Choose the best answer regarding physician-assisted suicide in the United States:

A. It is now legal in most states.

B. Under California law, assisting or causing one to commit suicide, including physician-assisted suicide, still remains a felony.

C. Both the U.S. Supreme Court and the New York Court of Appeals have held there is no constitutional right to physician-assisted suicide.

D. The American Medical Association is neutral on the issue.

E. Pain relief is the overriding reason for patients who request physician-assisted suicide.

Answer: C. We reviewed this topic in one of our regular columns in 2013.¹ At that time, efforts to legalize physician-assisted suicide (PAS) appeared to be gathering momentum across the country, with four jurisdictions having legalized the practice, beginning with Oregon in 1994. The other states were Washington, Vermont, and Montana, whose Supreme Court held that there was no public interest reason against the practice.²

Since that time, California, Colorado, and the District of Columbia have joined the group. Currently, PAS – but not euthanasia – is legally available in these jurisdictions and in Switzerland, but both can be legally practiced in Belgium, Canada, Colombia, Luxembourg, and the Netherlands.

All state statutes permitting PAS provide similar provisions and safeguards. Only competent individuals who are terminally ill, i.e., death expected within 6 months, can make a request for a lethal dose of medication to carry out the suicidal act. The request to the doctor is first made verbally, then in writing, and a second opinion must be obtained to confirm the patient’s intent, understanding, and free choice. There is also a waiting period.

Public support for euthanasia and PAS in the United States is said to have plateaued since the 1990s. But a significant number of Americans, 67%, still favor PAS, up from 56% a decade ago.³ However, not many patients resort to PAS – usually those with terminal cancers or neuromuscular conditions – and only a minority of physicians are participants.

For example, 61 physicians in Oregon wrote a total of 115 prescriptions in 2012; there were 77 known Death With Dignity Act deaths in Oregon that year.⁴ In Oregon and Washington State, less than 1% of licensed physicians write prescriptions for physician-assisted suicide each year. In contrast, about half or more of physicians in the Netherlands and Belgium reported ever having received a request, and 60% of Dutch physicians have granted such requests.

The California Department of Public Health reported that 111 terminally ill patients availed themselves of California’s End of Life Option Act in the 7 months after it became effective on June 9, 2016.

In a recent review on euthanasia and PAS for the period 1947-2016, Ezekiel Emanuel, MD, and colleagues noted that typical patients were older, white, and well educated, and pain was mostly not reported as the primary motivation.⁵ A large portion of patients receiving PAS in Oregon and Washington were enrolled in hospice or palliative care. Abuses have not been apparent.

In the vast majority of jurisdictions, assisting or causing one to commit suicide, including PAS, still remains a crime; for example, it is considered manslaughter under Hawaii state law §707-702.

In distinguishing between assisting suicide and withdrawing life-sustaining treatment, the U.S. Supreme Court’s landmark 1997 Vacco v. Quill decision emphasized issues of causation and intent.⁶ On causation, the court reasoned that when a patient refuses life-sustaining treatment, he dies from an underlying fatal disease; but if a patient ingests a lethal medication, he is killed by that medication. As to intent, a physician who honors a patient’s refusal of treatment purposefully intends only to respect his patient’s wishes and to cease doing futile or degrading things. On the other hand, a doctor who assists a suicide “must, necessarily and indubitably, intend primarily that the patient be made dead.”

In its companion case Washington v. Glucksberg, the Supreme Court held that the asserted “right” to assistance in committing suicide is not a fundamental liberty interest protected by the due process clause.⁷

State supreme courts in Florida, New Mexico, and elsewhere have likewise rebuffed claims of any constitutional right to PAS. The latest court to so rule is in New York, which has a long history of criminalizing assisted suicide.⁸ The New York Court of Appeals recently addressed claims brought by three terminally ill individuals, several medical providers, and a nonprofit entity seeking a declaration that New York’s “assisted suicide” statutes exclude physicians from prescribing a lethal dose of drugs to terminally ill, competent patients.

The court unequivocally rejected such claims and affirmed that a physician who assists a suicide by prescribing lethal doses of drugs is subject to criminal prosecution for second-degree manslaughter. It refused to regard PAS as being different from assisted suicide in general, and it rejected the constitutional claim to assisted suicide by a terminally ill person. The state appeals court reiterated the U.S. Supreme Court’s distinction between refusing life-sustaining treatment and assisted suicide, the former being “at least partially rooted in notions of bodily integrity, as the right to refuse treatment is a consequence of a person’s right to resist unwanted bodily invasions.” The New York Court of Appeals also noted that the state has a legitimate purpose and a rational basis for guarding against the risks of mistake and abuse.

These developments may signal a shift away from the legalization of PAS, as recently suggested in a Washington Post article.⁹ According to the end-of-life advocacy organization Compassion and Choices, none of the 27 states where such measures were introduced in 2017 passed them into law, including states such as Connecticut, Hawaii, and Rhode Island. In Central and Eastern Europe, support is decreasing, whereas the opposite is true in Western Europe.

U.S. federal lawmakers also appear to be pushing back. On July 13, 2017, the U.S. House Committee on Appropriations voted to block implementation of a “death with dignity” statute passed by the District of Columbia. Further, 11 House members – including 6 Democrats – have introduced a resolution asserting that PAS undermines a key safeguard that protects our nation’s most vulnerable citizens, including the elderly, people with disabilities, and people experiencing psychiatric diagnoses.¹⁰

The American Medical Association is steadfast in its opposition to PAS and euthanasia. In its latest Code of Ethics, the AMA reaffirmed its long-held position that “allowing physicians to engage in assisted suicide would cause more harm than good. Physician-assisted suicide is fundamentally incompatible with the physician’s role as healer, would be difficult or impossible to control, and would pose serious societal risks. … Instead of participating in assisted suicide, physicians must aggressively respond to the needs of patients at the end of life.”¹¹

References

1. “Physician-assisted suicide,” Internal Medicine News, Oct. 14, 2013.

2. Baxter v. State of Montana, 224 P. 3d 1211 (2010).

3. “Majority of Americans Remain Supportive of Euthanasia,” Gallup News, June 12, 2017.

4. Statistics available at public.health.oregon.gov under Oregon Death with Dignity Act.

5. JAMA. 2016 Jul 5;316(1):79-90.

6. Vacco v. Quill, 117 S. Ct. 2293 (1997).

7. Washington v. Glucksberg, 521 U.S. 702 (1997).

8. Myers v. Schneiderman, New York Court of Appeals, 2017.

9. “Legalizing assisted suicide has stalled at every level,” Washington Post, Oct. 24, 2017.

10. H. Con. Res. 80, 115th Congress (2017-2018).

11. AMA Code of Medical Ethics §5.7 (2017).