A 37-year-old Caucasian man sought care at our clinic for the pruritic patches on his trunk and extremities that had developed 3 days earlier. The patient said that the lesions started on his right arm but had spread to his left arm, posterior legs, and trunk. He reported that the trunk lesions had resolved, but the extremity lesions persisted. He’d had no specific contact exposures.

Upon further questioning, the patient indicated that he had noted the pigmented patch for at least 4 years, but was not sure how long the nodular area had been there. He thought it was a birthmark. He grew up spending a lot of time at the beach in the sun and recalled at least one blistering sunburn on his back.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient underwent elliptical excisional biopsy of the primary lesion after no palpable lymphadenopathy was noted. The lateral and deep margins were negative for melanoma; the mitotic rate was <1/mm². Aggregates of lymphocytes were associated with the lesion, but did not infiltrate it. There was no tumor regression or ulceration of the lesion. The Breslow depth was 1.25 mm.

A histopathologic evaluation revealed a superficial spreading melanoma (inferior lesion in the FIGURE) and a nodular lesion (the superior reddish-black lesion in the FIGURE). (For more on these and other forms of melanoma, see “The 4 main types of melanoma”^1-4 see below.) It was unclear from the patient’s history whether this represented 2 types of melanoma (superficial spreading and nodular) in the same field of skin or the development of a nodular component in a superficial spreading lesion. Important clinical information was also missing, including the evolution of the lesions and how quickly the nodule had grown.

The preferred method for biopsy is complete elliptical excision with 2- to 3-mm margins of normal skin.

Who’s affected most? More than 45,000 cases of melanoma occurred in 45 states and the District of Columbia annually between 2004 and 2006, according to a 2011 report from the Centers for Disease Control and Prevention.⁵ White, non-Hispanics have a far higher incidence of melanoma than any other race or ethnicity.⁶ Women are more likely than men to be diagnosed with melanoma early in life, while men are twice as likely as women to be diagnosed after age 60.⁶ The etiology for the malignant transformation of melanocytes has not been fully clarified, but it is likely multifactorial, including genetic susceptibility and ultraviolet (UV) radiation damage.⁴

The ABCDE mnemonic is widely taught to aid in the detection of melanomas: A = asymmetry of the lesion; B = border irregularities; C = color variegation; D = diameter >6 mm; and E = evolution. The evolution of the lesion has been shown in some studies to be the most specific finding for detecting melanomas.⁴

Regional lymph nodes should also be carefully examined for evidence of clinical spread prior to biopsy of a suspicious lesion. This is important because biopsy may cause regional lymphadenopathy, which could confound later examinations and staging of the disease.¹

The differential: Is it a worrisome lesion—or not?
The differential diagnosis of melanoma includes both benign and malignant lesions. Malignant and potentially malignant diagnoses to consider include pigmented basal cell carcinoma, pigmented squamous cell carcinoma, carcinoma metastatic to the skin, and dysplastic nevi.^2,3

Benign diagnoses to consider include pigmented seborrheic keratoses, lentigo, pyogenic granuloma, Kaposi sarcoma, cherry angioma, subungual traumatic hematoma, dermatofibroma, and nevi (including blue nevi).^2,3

The biopsy is paramount
A diagnosis is established based on the microscopic evaluation of suspicious lesions. Studies suggest that one-third to one-half of melanomas arise from existing nevi, with the remainder developing from previously normal-appearing skin.^1,2 Patients with increased numbers of either common or dysplastic nevi are at increased risk of melanoma compared with the general population.⁴ Historical clues include changes in a lesion’s size, color, or symmetry; new growths; personal or family history of melanoma; and bleeding.

A biopsy for histopathologic evaluation is mandatory when a lesion is suspicious for melanoma. Dermoscopy, which involves a device that magnifies skin lesions, may reveal highly specific dermoscopic features for melanoma that can help in determining the need for biopsy.⁴

The preferred method for biopsy is complete elliptical excision with 2- to 3-mm margins of normal skin.^2,3 However, a deep shave biopsy may also be appropriate, depending upon the clinical situation and physician experience with the technique.⁴

A deep shave biopsy is less time consuming than elliptical excision, making it easier to perform at the time the lesion is first evaluated. Deep shave biopsy may provide several benefits, including reducing the amount of normal tissue that is removed (especially if pathology is benign) as well as, the cost, scarring, and likelihood of wound infections. Deep shave biopsy also can avoid the need for a second elliptical excision.^7,8

Determine margins, proceed with surgical excision
Early surgical excision is the primary treatment for malignant melanoma. After the diagnosis is confirmed by initial biopsy, the depth of the lesion dictates the surgical recommendations. Recommended surgical margins based on depth are: 5 mm with a layer of subcutaneous fat for melanoma in situ, 1 cm down to the fascia for lesions with a Breslow depth ≤2 mm, and 2 cm down to the fascia for lesions with a depth >2 mm.^1,4

The surgical treatment of lentigo maligna melanoma can be challenging due to indistinct borders and large size. Mohs micrographic surgery can be helpful to fully remove the lesion with sparing of healthy surrounding tissue.⁴ When surgical excision of large lentigo maligna is technically difficult, radiation therapy is another option.³

Subungual melanoma may necessitate amputation or grafting of the digit. Mohs micrographic surgery can be useful in these situations for tissue sparing.² (To learn more, see “When to consider Mohs surgery,” J Fam Pract. 2013;558-564.)

Is a sentinel lymph node biopsy needed?
Sentinel lymph node biopsy is often recommended for melanomas >1 mm in depth.^2-4 It provides guidance on who may benefit from regional lymphadenectomy and adjuvant immunotherapy.^1,3

Adjuvant therapy for patients without evidence of distant metastases can be considered in patients with positive nodes or node-negative melanoma that is 4 mm thick or Clark Level IV or V. Adjuvant high-dose interferon alpha-2b is the most commonly used agent in these situations.² Some studies suggest an increase in median overall survival of up to 11 months with high-dose interferon as compared to no treatment.³ Limitations include toxicity from these high-dose regimens.³ Treatment with interferon does not represent a cure; rather, it should be considered a palliative intervention with marginal benefit.¹

When there are distant metastases…
Once distant metastases are identified, the goal of therapy should be palliative care as this condition is generally incurable. Chemotherapy, radiation, and excision of solitary metastases are all interventions that have traditionally been employed.¹ The primary site for metastasis is the skin, but all organs are potential sites of spread. Central nervous system metastasis is the most common cause of the death.²

Novel therapies include inhibition of BRAF, an enzyme of the mitogen-activated protein kinase pathway (MAPK), and blocking of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4).

Sentinel lymph node biopsy is often recommended for melanomas >1 mm in depth.

BRAF-enzyme inhibitor. Mutated BRAF contributes to uncontrolled cell growth and resistance to programmed cell death (apoptosis).^9,10 In August 2011, vemurafenib (Zelboraf ), a BRAF-enzyme inhibitor, was approved by the US Food and Drug Administration (FDA) for the treatment of late-stage melanoma. It works only in patients with the BRAF^V600E mutation, which is found in approximately 60% of melanomas.^11,12 One phase 1 study showed partial to complete regression in 80% of patients treated, but this regression lasted only 2 to 18 months.¹³

Anti-CTLA-4 monoclonal antibody. Cytotoxic T-lymphocytes can recognize and potentially destroy cancer cells.¹⁴ However, CTLA-4, which is expressed on the surface of cytotoxic T-lymphocytes, has a suppressive effect on the T-lymphocyte response after interaction with the antigen-presenting cell. Researchers deduced that blocking CTLA-4 would allow the immune system to remain responsive to abnormal antigens, including those from melanoma.⁹

Ipilimumab (Yervoy), an anti-CTLA-4 monoclonal antibody, was approved by the FDA in March 2011 for the treatment of late-stage melanoma.¹¹ Partial and complete responses have been shown in trials of ipilimumab as monotherapy and in combination with vaccines, chemotherapy, and interleukin-2, but these responses have not been sustained.⁹

Although these novel therapies represent significant advancements in the understanding of the pathogenesis of melanoma, the short duration of efficacy highlights the cancer’s ability to develop resistance to these treatments. This ability to adapt suggests that melanoma harbors multiple oncogenes and several pathways for carcinogenesis. Combination targeted therapies may be required to improve clinical results; research is ongoing.⁹ Toxicities associated with these medications are also a limiting factor.

What about vaccines? Vaccine studies are also ongoing. Although some have shown promising results, no clearly effective therapy has been produced to date.²

Factors that affect prognosis
The prognosis for melanoma is related to tumor thickness, presence or absence of melanoma in regional lymph nodes, and extent of metastases.^1-4 The TNM classification system takes these factors into account in staging melanoma.⁴ Based on this staging, a 5- and 10-year survival estimate can be discussed with the patient.

Survival estimates based on depth of invasion alone are also used. As an example, one study cited a 5-year survival rate of 95% for a tumor thickness <.75 mm; 85% (.75-1.4 mm); 66% (1.5-3.9 mm); and 46% (≥4 mm).¹

Other variables that affect prognosis include lymphocytic infiltrate (more brisk and tumor infiltrating is better prognostically), mitotic rate (less is better; >6/mm² is worse), ulceration (worse prognostically), and regression of the tumor.² Regression will appear as areas of depigmentation in a previously completely pigmented lesion; it is associated with a poorer prognosis.¹

Follow-up with patients is key
Regular skin, lymph node, and general follow-up exams are recommended to detect metastatic disease or new primary lesions. It has been estimated that approximately 5% of patients with a history of melanoma will develop a new primary lesion.³ Lab and imaging studies should be used when prompted by clinical findings.²

Some protocols recommend routine use of labs, including lactate dehydrogenase, complete blood count, and chemistries, as well as imaging such as chest x-ray, positron emission tomography (PET), or computed tomography (CT) based on the stage of the disease.⁴ No evidence has shown that routine laboratory or imaging studies affect prognosis.²

The reggae legend Bob Marley died at age 36 from metastatic subungual melanoma of the foot.

Close surveillance for my patient
My patient underwent re-excision of the tumor site with wide margins. Sentinel lymph nodes excised from the bilateral axilla were negative for melanoma. He was seen by colleagues in the oncology department, and his lab work and chest x-ray were normal. PET/CT revealed no evidence of fluorodeoxyglucose avid metastatic disease.

Based on staging, my patient’s 5-year survival was estimated at 81% and his 10-year survival at 67%. No further oncology follow-up was planned and the patient was instructed to be seen by a dermatologist for close clinical surveillance.

CORRESPONDENCE
Suresh K. Menon, MD, Hahn Medical Practices, 5078 Williamsport Pike, Martinsburg, WV 25404; [email protected]

A 37-year-old Caucasian man sought care at our clinic for the pruritic patches on his trunk and extremities that had developed 3 days earlier. The patient said that the lesions started on his right arm but had spread to his left arm, posterior legs, and trunk. He reported that the trunk lesions had resolved, but the extremity lesions persisted. He’d had no specific contact exposures.

Upon further questioning, the patient indicated that he had noted the pigmented patch for at least 4 years, but was not sure how long the nodular area had been there. He thought it was a birthmark. He grew up spending a lot of time at the beach in the sun and recalled at least one blistering sunburn on his back.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient underwent elliptical excisional biopsy of the primary lesion after no palpable lymphadenopathy was noted. The lateral and deep margins were negative for melanoma; the mitotic rate was <1/mm². Aggregates of lymphocytes were associated with the lesion, but did not infiltrate it. There was no tumor regression or ulceration of the lesion. The Breslow depth was 1.25 mm.

A histopathologic evaluation revealed a superficial spreading melanoma (inferior lesion in the FIGURE) and a nodular lesion (the superior reddish-black lesion in the FIGURE). (For more on these and other forms of melanoma, see “The 4 main types of melanoma”^1-4 see below.) It was unclear from the patient’s history whether this represented 2 types of melanoma (superficial spreading and nodular) in the same field of skin or the development of a nodular component in a superficial spreading lesion. Important clinical information was also missing, including the evolution of the lesions and how quickly the nodule had grown.

The preferred method for biopsy is complete elliptical excision with 2- to 3-mm margins of normal skin.

Who’s affected most? More than 45,000 cases of melanoma occurred in 45 states and the District of Columbia annually between 2004 and 2006, according to a 2011 report from the Centers for Disease Control and Prevention.⁵ White, non-Hispanics have a far higher incidence of melanoma than any other race or ethnicity.⁶ Women are more likely than men to be diagnosed with melanoma early in life, while men are twice as likely as women to be diagnosed after age 60.⁶ The etiology for the malignant transformation of melanocytes has not been fully clarified, but it is likely multifactorial, including genetic susceptibility and ultraviolet (UV) radiation damage.⁴

The ABCDE mnemonic is widely taught to aid in the detection of melanomas: A = asymmetry of the lesion; B = border irregularities; C = color variegation; D = diameter >6 mm; and E = evolution. The evolution of the lesion has been shown in some studies to be the most specific finding for detecting melanomas.⁴

Regional lymph nodes should also be carefully examined for evidence of clinical spread prior to biopsy of a suspicious lesion. This is important because biopsy may cause regional lymphadenopathy, which could confound later examinations and staging of the disease.¹

The differential: Is it a worrisome lesion—or not?
The differential diagnosis of melanoma includes both benign and malignant lesions. Malignant and potentially malignant diagnoses to consider include pigmented basal cell carcinoma, pigmented squamous cell carcinoma, carcinoma metastatic to the skin, and dysplastic nevi.^2,3

Benign diagnoses to consider include pigmented seborrheic keratoses, lentigo, pyogenic granuloma, Kaposi sarcoma, cherry angioma, subungual traumatic hematoma, dermatofibroma, and nevi (including blue nevi).^2,3

The biopsy is paramount
A diagnosis is established based on the microscopic evaluation of suspicious lesions. Studies suggest that one-third to one-half of melanomas arise from existing nevi, with the remainder developing from previously normal-appearing skin.^1,2 Patients with increased numbers of either common or dysplastic nevi are at increased risk of melanoma compared with the general population.⁴ Historical clues include changes in a lesion’s size, color, or symmetry; new growths; personal or family history of melanoma; and bleeding.

A biopsy for histopathologic evaluation is mandatory when a lesion is suspicious for melanoma. Dermoscopy, which involves a device that magnifies skin lesions, may reveal highly specific dermoscopic features for melanoma that can help in determining the need for biopsy.⁴

The preferred method for biopsy is complete elliptical excision with 2- to 3-mm margins of normal skin.^2,3 However, a deep shave biopsy may also be appropriate, depending upon the clinical situation and physician experience with the technique.⁴

A deep shave biopsy is less time consuming than elliptical excision, making it easier to perform at the time the lesion is first evaluated. Deep shave biopsy may provide several benefits, including reducing the amount of normal tissue that is removed (especially if pathology is benign) as well as, the cost, scarring, and likelihood of wound infections. Deep shave biopsy also can avoid the need for a second elliptical excision.^7,8

Determine margins, proceed with surgical excision
Early surgical excision is the primary treatment for malignant melanoma. After the diagnosis is confirmed by initial biopsy, the depth of the lesion dictates the surgical recommendations. Recommended surgical margins based on depth are: 5 mm with a layer of subcutaneous fat for melanoma in situ, 1 cm down to the fascia for lesions with a Breslow depth ≤2 mm, and 2 cm down to the fascia for lesions with a depth >2 mm.^1,4

The surgical treatment of lentigo maligna melanoma can be challenging due to indistinct borders and large size. Mohs micrographic surgery can be helpful to fully remove the lesion with sparing of healthy surrounding tissue.⁴ When surgical excision of large lentigo maligna is technically difficult, radiation therapy is another option.³

Subungual melanoma may necessitate amputation or grafting of the digit. Mohs micrographic surgery can be useful in these situations for tissue sparing.² (To learn more, see “When to consider Mohs surgery,” J Fam Pract. 2013;558-564.)

Is a sentinel lymph node biopsy needed?
Sentinel lymph node biopsy is often recommended for melanomas >1 mm in depth.^2-4 It provides guidance on who may benefit from regional lymphadenectomy and adjuvant immunotherapy.^1,3

Adjuvant therapy for patients without evidence of distant metastases can be considered in patients with positive nodes or node-negative melanoma that is 4 mm thick or Clark Level IV or V. Adjuvant high-dose interferon alpha-2b is the most commonly used agent in these situations.² Some studies suggest an increase in median overall survival of up to 11 months with high-dose interferon as compared to no treatment.³ Limitations include toxicity from these high-dose regimens.³ Treatment with interferon does not represent a cure; rather, it should be considered a palliative intervention with marginal benefit.¹

When there are distant metastases…
Once distant metastases are identified, the goal of therapy should be palliative care as this condition is generally incurable. Chemotherapy, radiation, and excision of solitary metastases are all interventions that have traditionally been employed.¹ The primary site for metastasis is the skin, but all organs are potential sites of spread. Central nervous system metastasis is the most common cause of the death.²

Novel therapies include inhibition of BRAF, an enzyme of the mitogen-activated protein kinase pathway (MAPK), and blocking of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4).

Sentinel lymph node biopsy is often recommended for melanomas >1 mm in depth.

BRAF-enzyme inhibitor. Mutated BRAF contributes to uncontrolled cell growth and resistance to programmed cell death (apoptosis).^9,10 In August 2011, vemurafenib (Zelboraf ), a BRAF-enzyme inhibitor, was approved by the US Food and Drug Administration (FDA) for the treatment of late-stage melanoma. It works only in patients with the BRAF^V600E mutation, which is found in approximately 60% of melanomas.^11,12 One phase 1 study showed partial to complete regression in 80% of patients treated, but this regression lasted only 2 to 18 months.¹³

Anti-CTLA-4 monoclonal antibody. Cytotoxic T-lymphocytes can recognize and potentially destroy cancer cells.¹⁴ However, CTLA-4, which is expressed on the surface of cytotoxic T-lymphocytes, has a suppressive effect on the T-lymphocyte response after interaction with the antigen-presenting cell. Researchers deduced that blocking CTLA-4 would allow the immune system to remain responsive to abnormal antigens, including those from melanoma.⁹

Ipilimumab (Yervoy), an anti-CTLA-4 monoclonal antibody, was approved by the FDA in March 2011 for the treatment of late-stage melanoma.¹¹ Partial and complete responses have been shown in trials of ipilimumab as monotherapy and in combination with vaccines, chemotherapy, and interleukin-2, but these responses have not been sustained.⁹

Although these novel therapies represent significant advancements in the understanding of the pathogenesis of melanoma, the short duration of efficacy highlights the cancer’s ability to develop resistance to these treatments. This ability to adapt suggests that melanoma harbors multiple oncogenes and several pathways for carcinogenesis. Combination targeted therapies may be required to improve clinical results; research is ongoing.⁹ Toxicities associated with these medications are also a limiting factor.

What about vaccines? Vaccine studies are also ongoing. Although some have shown promising results, no clearly effective therapy has been produced to date.²

Factors that affect prognosis
The prognosis for melanoma is related to tumor thickness, presence or absence of melanoma in regional lymph nodes, and extent of metastases.^1-4 The TNM classification system takes these factors into account in staging melanoma.⁴ Based on this staging, a 5- and 10-year survival estimate can be discussed with the patient.

Survival estimates based on depth of invasion alone are also used. As an example, one study cited a 5-year survival rate of 95% for a tumor thickness <.75 mm; 85% (.75-1.4 mm); 66% (1.5-3.9 mm); and 46% (≥4 mm).¹

Other variables that affect prognosis include lymphocytic infiltrate (more brisk and tumor infiltrating is better prognostically), mitotic rate (less is better; >6/mm² is worse), ulceration (worse prognostically), and regression of the tumor.² Regression will appear as areas of depigmentation in a previously completely pigmented lesion; it is associated with a poorer prognosis.¹

Follow-up with patients is key
Regular skin, lymph node, and general follow-up exams are recommended to detect metastatic disease or new primary lesions. It has been estimated that approximately 5% of patients with a history of melanoma will develop a new primary lesion.³ Lab and imaging studies should be used when prompted by clinical findings.²

Some protocols recommend routine use of labs, including lactate dehydrogenase, complete blood count, and chemistries, as well as imaging such as chest x-ray, positron emission tomography (PET), or computed tomography (CT) based on the stage of the disease.⁴ No evidence has shown that routine laboratory or imaging studies affect prognosis.²

The reggae legend Bob Marley died at age 36 from metastatic subungual melanoma of the foot.

Close surveillance for my patient
My patient underwent re-excision of the tumor site with wide margins. Sentinel lymph nodes excised from the bilateral axilla were negative for melanoma. He was seen by colleagues in the oncology department, and his lab work and chest x-ray were normal. PET/CT revealed no evidence of fluorodeoxyglucose avid metastatic disease.

Based on staging, my patient’s 5-year survival was estimated at 81% and his 10-year survival at 67%. No further oncology follow-up was planned and the patient was instructed to be seen by a dermatologist for close clinical surveillance.

CORRESPONDENCE
Suresh K. Menon, MD, Hahn Medical Practices, 5078 Williamsport Pike, Martinsburg, WV 25404; [email protected]

A 37-year-old Caucasian man sought care at our clinic for the pruritic patches on his trunk and extremities that had developed 3 days earlier. The patient said that the lesions started on his right arm but had spread to his left arm, posterior legs, and trunk. He reported that the trunk lesions had resolved, but the extremity lesions persisted. He’d had no specific contact exposures.

Upon further questioning, the patient indicated that he had noted the pigmented patch for at least 4 years, but was not sure how long the nodular area had been there. He thought it was a birthmark. He grew up spending a lot of time at the beach in the sun and recalled at least one blistering sunburn on his back.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient underwent elliptical excisional biopsy of the primary lesion after no palpable lymphadenopathy was noted. The lateral and deep margins were negative for melanoma; the mitotic rate was <1/mm². Aggregates of lymphocytes were associated with the lesion, but did not infiltrate it. There was no tumor regression or ulceration of the lesion. The Breslow depth was 1.25 mm.

A histopathologic evaluation revealed a superficial spreading melanoma (inferior lesion in the FIGURE) and a nodular lesion (the superior reddish-black lesion in the FIGURE). (For more on these and other forms of melanoma, see “The 4 main types of melanoma”^1-4 see below.) It was unclear from the patient’s history whether this represented 2 types of melanoma (superficial spreading and nodular) in the same field of skin or the development of a nodular component in a superficial spreading lesion. Important clinical information was also missing, including the evolution of the lesions and how quickly the nodule had grown.

The preferred method for biopsy is complete elliptical excision with 2- to 3-mm margins of normal skin.

Who’s affected most? More than 45,000 cases of melanoma occurred in 45 states and the District of Columbia annually between 2004 and 2006, according to a 2011 report from the Centers for Disease Control and Prevention.⁵ White, non-Hispanics have a far higher incidence of melanoma than any other race or ethnicity.⁶ Women are more likely than men to be diagnosed with melanoma early in life, while men are twice as likely as women to be diagnosed after age 60.⁶ The etiology for the malignant transformation of melanocytes has not been fully clarified, but it is likely multifactorial, including genetic susceptibility and ultraviolet (UV) radiation damage.⁴

The ABCDE mnemonic is widely taught to aid in the detection of melanomas: A = asymmetry of the lesion; B = border irregularities; C = color variegation; D = diameter >6 mm; and E = evolution. The evolution of the lesion has been shown in some studies to be the most specific finding for detecting melanomas.⁴

Regional lymph nodes should also be carefully examined for evidence of clinical spread prior to biopsy of a suspicious lesion. This is important because biopsy may cause regional lymphadenopathy, which could confound later examinations and staging of the disease.¹

The differential: Is it a worrisome lesion—or not?
The differential diagnosis of melanoma includes both benign and malignant lesions. Malignant and potentially malignant diagnoses to consider include pigmented basal cell carcinoma, pigmented squamous cell carcinoma, carcinoma metastatic to the skin, and dysplastic nevi.^2,3

Benign diagnoses to consider include pigmented seborrheic keratoses, lentigo, pyogenic granuloma, Kaposi sarcoma, cherry angioma, subungual traumatic hematoma, dermatofibroma, and nevi (including blue nevi).^2,3

The biopsy is paramount
A diagnosis is established based on the microscopic evaluation of suspicious lesions. Studies suggest that one-third to one-half of melanomas arise from existing nevi, with the remainder developing from previously normal-appearing skin.^1,2 Patients with increased numbers of either common or dysplastic nevi are at increased risk of melanoma compared with the general population.⁴ Historical clues include changes in a lesion’s size, color, or symmetry; new growths; personal or family history of melanoma; and bleeding.

A biopsy for histopathologic evaluation is mandatory when a lesion is suspicious for melanoma. Dermoscopy, which involves a device that magnifies skin lesions, may reveal highly specific dermoscopic features for melanoma that can help in determining the need for biopsy.⁴

The preferred method for biopsy is complete elliptical excision with 2- to 3-mm margins of normal skin.^2,3 However, a deep shave biopsy may also be appropriate, depending upon the clinical situation and physician experience with the technique.⁴

A deep shave biopsy is less time consuming than elliptical excision, making it easier to perform at the time the lesion is first evaluated. Deep shave biopsy may provide several benefits, including reducing the amount of normal tissue that is removed (especially if pathology is benign) as well as, the cost, scarring, and likelihood of wound infections. Deep shave biopsy also can avoid the need for a second elliptical excision.^7,8

Determine margins, proceed with surgical excision
Early surgical excision is the primary treatment for malignant melanoma. After the diagnosis is confirmed by initial biopsy, the depth of the lesion dictates the surgical recommendations. Recommended surgical margins based on depth are: 5 mm with a layer of subcutaneous fat for melanoma in situ, 1 cm down to the fascia for lesions with a Breslow depth ≤2 mm, and 2 cm down to the fascia for lesions with a depth >2 mm.^1,4

The surgical treatment of lentigo maligna melanoma can be challenging due to indistinct borders and large size. Mohs micrographic surgery can be helpful to fully remove the lesion with sparing of healthy surrounding tissue.⁴ When surgical excision of large lentigo maligna is technically difficult, radiation therapy is another option.³

Subungual melanoma may necessitate amputation or grafting of the digit. Mohs micrographic surgery can be useful in these situations for tissue sparing.² (To learn more, see “When to consider Mohs surgery,” J Fam Pract. 2013;558-564.)

Is a sentinel lymph node biopsy needed?
Sentinel lymph node biopsy is often recommended for melanomas >1 mm in depth.^2-4 It provides guidance on who may benefit from regional lymphadenectomy and adjuvant immunotherapy.^1,3

Adjuvant therapy for patients without evidence of distant metastases can be considered in patients with positive nodes or node-negative melanoma that is 4 mm thick or Clark Level IV or V. Adjuvant high-dose interferon alpha-2b is the most commonly used agent in these situations.² Some studies suggest an increase in median overall survival of up to 11 months with high-dose interferon as compared to no treatment.³ Limitations include toxicity from these high-dose regimens.³ Treatment with interferon does not represent a cure; rather, it should be considered a palliative intervention with marginal benefit.¹

When there are distant metastases…
Once distant metastases are identified, the goal of therapy should be palliative care as this condition is generally incurable. Chemotherapy, radiation, and excision of solitary metastases are all interventions that have traditionally been employed.¹ The primary site for metastasis is the skin, but all organs are potential sites of spread. Central nervous system metastasis is the most common cause of the death.²

Novel therapies include inhibition of BRAF, an enzyme of the mitogen-activated protein kinase pathway (MAPK), and blocking of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4).

Sentinel lymph node biopsy is often recommended for melanomas >1 mm in depth.

BRAF-enzyme inhibitor. Mutated BRAF contributes to uncontrolled cell growth and resistance to programmed cell death (apoptosis).^9,10 In August 2011, vemurafenib (Zelboraf ), a BRAF-enzyme inhibitor, was approved by the US Food and Drug Administration (FDA) for the treatment of late-stage melanoma. It works only in patients with the BRAF^V600E mutation, which is found in approximately 60% of melanomas.^11,12 One phase 1 study showed partial to complete regression in 80% of patients treated, but this regression lasted only 2 to 18 months.¹³

Anti-CTLA-4 monoclonal antibody. Cytotoxic T-lymphocytes can recognize and potentially destroy cancer cells.¹⁴ However, CTLA-4, which is expressed on the surface of cytotoxic T-lymphocytes, has a suppressive effect on the T-lymphocyte response after interaction with the antigen-presenting cell. Researchers deduced that blocking CTLA-4 would allow the immune system to remain responsive to abnormal antigens, including those from melanoma.⁹

Ipilimumab (Yervoy), an anti-CTLA-4 monoclonal antibody, was approved by the FDA in March 2011 for the treatment of late-stage melanoma.¹¹ Partial and complete responses have been shown in trials of ipilimumab as monotherapy and in combination with vaccines, chemotherapy, and interleukin-2, but these responses have not been sustained.⁹

Although these novel therapies represent significant advancements in the understanding of the pathogenesis of melanoma, the short duration of efficacy highlights the cancer’s ability to develop resistance to these treatments. This ability to adapt suggests that melanoma harbors multiple oncogenes and several pathways for carcinogenesis. Combination targeted therapies may be required to improve clinical results; research is ongoing.⁹ Toxicities associated with these medications are also a limiting factor.

What about vaccines? Vaccine studies are also ongoing. Although some have shown promising results, no clearly effective therapy has been produced to date.²

Factors that affect prognosis
The prognosis for melanoma is related to tumor thickness, presence or absence of melanoma in regional lymph nodes, and extent of metastases.^1-4 The TNM classification system takes these factors into account in staging melanoma.⁴ Based on this staging, a 5- and 10-year survival estimate can be discussed with the patient.

Survival estimates based on depth of invasion alone are also used. As an example, one study cited a 5-year survival rate of 95% for a tumor thickness <.75 mm; 85% (.75-1.4 mm); 66% (1.5-3.9 mm); and 46% (≥4 mm).¹

Other variables that affect prognosis include lymphocytic infiltrate (more brisk and tumor infiltrating is better prognostically), mitotic rate (less is better; >6/mm² is worse), ulceration (worse prognostically), and regression of the tumor.² Regression will appear as areas of depigmentation in a previously completely pigmented lesion; it is associated with a poorer prognosis.¹

Follow-up with patients is key
Regular skin, lymph node, and general follow-up exams are recommended to detect metastatic disease or new primary lesions. It has been estimated that approximately 5% of patients with a history of melanoma will develop a new primary lesion.³ Lab and imaging studies should be used when prompted by clinical findings.²

Some protocols recommend routine use of labs, including lactate dehydrogenase, complete blood count, and chemistries, as well as imaging such as chest x-ray, positron emission tomography (PET), or computed tomography (CT) based on the stage of the disease.⁴ No evidence has shown that routine laboratory or imaging studies affect prognosis.²

The reggae legend Bob Marley died at age 36 from metastatic subungual melanoma of the foot.

Close surveillance for my patient
My patient underwent re-excision of the tumor site with wide margins. Sentinel lymph nodes excised from the bilateral axilla were negative for melanoma. He was seen by colleagues in the oncology department, and his lab work and chest x-ray were normal. PET/CT revealed no evidence of fluorodeoxyglucose avid metastatic disease.

Based on staging, my patient’s 5-year survival was estimated at 81% and his 10-year survival at 67%. No further oncology follow-up was planned and the patient was instructed to be seen by a dermatologist for close clinical surveillance.

CORRESPONDENCE
Suresh K. Menon, MD, Hahn Medical Practices, 5078 Williamsport Pike, Martinsburg, WV 25404; [email protected]

My coauthors and I appreciate the comments of Drs. Mayer and Hansen. Regarding the cost effectiveness and utility of the Unna boot, we would point out that the focus of our Clinical Inquiry was on the initial management of venous stasis ulcers and how best to promote healing.

Little data exist on Unna boot application alone. But it is likely that many of the compression therapy modality studies in the Cochrane meta-analysis included in our review featured Unna boot dressings as part of some form of multilayer compression therapy being evaluated.¹

As Dr. Hansen observes, compression, the standard compression classes, and the minimal benefits of low pressure levels provided by the classic TED hose and OTC support hose should have been addressed. This information was not included in our review due to space limitations. This subject deserves a dedicated article, as there is a great deal of confusion about terminology and types of dressings.

Both the 2009 Cochrane meta-analysis¹ and a 2012 update² found that adding a component of elastic compression therapy results in faster ulcer healing compared with inelastic compression therapy alone. Venous ulcers treated with 4-layer bandages heal faster, on average, than those treated with short stretch bandages, and regular use of compression stockings lowers the risk of recurrence.³ Correcting underlying venous incompetency issues is certainly a consideration, particularly for ulcers that initially heal but later recur.

Mark Andrews, MD
Winston-Salem, NC

My coauthors and I appreciate the comments of Drs. Mayer and Hansen. Regarding the cost effectiveness and utility of the Unna boot, we would point out that the focus of our Clinical Inquiry was on the initial management of venous stasis ulcers and how best to promote healing.

Little data exist on Unna boot application alone. But it is likely that many of the compression therapy modality studies in the Cochrane meta-analysis included in our review featured Unna boot dressings as part of some form of multilayer compression therapy being evaluated.¹

As Dr. Hansen observes, compression, the standard compression classes, and the minimal benefits of low pressure levels provided by the classic TED hose and OTC support hose should have been addressed. This information was not included in our review due to space limitations. This subject deserves a dedicated article, as there is a great deal of confusion about terminology and types of dressings.

Both the 2009 Cochrane meta-analysis¹ and a 2012 update² found that adding a component of elastic compression therapy results in faster ulcer healing compared with inelastic compression therapy alone. Venous ulcers treated with 4-layer bandages heal faster, on average, than those treated with short stretch bandages, and regular use of compression stockings lowers the risk of recurrence.³ Correcting underlying venous incompetency issues is certainly a consideration, particularly for ulcers that initially heal but later recur.

Mark Andrews, MD
Winston-Salem, NC

My coauthors and I appreciate the comments of Drs. Mayer and Hansen. Regarding the cost effectiveness and utility of the Unna boot, we would point out that the focus of our Clinical Inquiry was on the initial management of venous stasis ulcers and how best to promote healing.

Little data exist on Unna boot application alone. But it is likely that many of the compression therapy modality studies in the Cochrane meta-analysis included in our review featured Unna boot dressings as part of some form of multilayer compression therapy being evaluated.¹

As Dr. Hansen observes, compression, the standard compression classes, and the minimal benefits of low pressure levels provided by the classic TED hose and OTC support hose should have been addressed. This information was not included in our review due to space limitations. This subject deserves a dedicated article, as there is a great deal of confusion about terminology and types of dressings.

Both the 2009 Cochrane meta-analysis¹ and a 2012 update² found that adding a component of elastic compression therapy results in faster ulcer healing compared with inelastic compression therapy alone. Venous ulcers treated with 4-layer bandages heal faster, on average, than those treated with short stretch bandages, and regular use of compression stockings lowers the risk of recurrence.³ Correcting underlying venous incompetency issues is certainly a consideration, particularly for ulcers that initially heal but later recur.

Mark Andrews, MD
Winston-Salem, NC

In “What is the best initial treatment for venous stasis ulcers?” (Clinical Inquiries. J Fam Pract. 2013;62:433-434), Dr. Poynter et al seemed to say that various kinds of compression stockings are suitable. What about going back to the Unna boot?

I have had great success treating venous stasis ulcers with the Unna boot. This calamine-infused gauze dressing, which can easily be applied in a primary care setting, has been replaced by wound treatments that are much more expensive—and may be less effective. Cost matters, and all things being equal, it’s time to promote the Unna boot once more.

Charles Mayer, MD, MPH
Seattle, Wash

As a family physician certified by the American Board of Venous and Lymphatic Disease, I would like to point out a couple of things.

First, while the authors discussed compression, they did not define what that meant. This is important, as many physicians prescribe TED hose for venous stasis ulcers, although it does not provide enough compression.

Secondly, fixing the underlying problem should be considered part of the initial treatment. Studies show that a combination of compression and intervention is the best way to ensure long-term healing of venous stasis ulcers.^1,2 I would recommend that such patients be referred to a phlebologist for evaluation. Compression alone has a poor long-term outcome for the healing of ulceration.

Lornell E. Hansen II, MD, FAAFP
Sioux Falls, SD

In “What is the best initial treatment for venous stasis ulcers?” (Clinical Inquiries. J Fam Pract. 2013;62:433-434), Dr. Poynter et al seemed to say that various kinds of compression stockings are suitable. What about going back to the Unna boot?

I have had great success treating venous stasis ulcers with the Unna boot. This calamine-infused gauze dressing, which can easily be applied in a primary care setting, has been replaced by wound treatments that are much more expensive—and may be less effective. Cost matters, and all things being equal, it’s time to promote the Unna boot once more.

Charles Mayer, MD, MPH
Seattle, Wash

As a family physician certified by the American Board of Venous and Lymphatic Disease, I would like to point out a couple of things.

First, while the authors discussed compression, they did not define what that meant. This is important, as many physicians prescribe TED hose for venous stasis ulcers, although it does not provide enough compression.

Secondly, fixing the underlying problem should be considered part of the initial treatment. Studies show that a combination of compression and intervention is the best way to ensure long-term healing of venous stasis ulcers.^1,2 I would recommend that such patients be referred to a phlebologist for evaluation. Compression alone has a poor long-term outcome for the healing of ulceration.

Lornell E. Hansen II, MD, FAAFP
Sioux Falls, SD

In “What is the best initial treatment for venous stasis ulcers?” (Clinical Inquiries. J Fam Pract. 2013;62:433-434), Dr. Poynter et al seemed to say that various kinds of compression stockings are suitable. What about going back to the Unna boot?

I have had great success treating venous stasis ulcers with the Unna boot. This calamine-infused gauze dressing, which can easily be applied in a primary care setting, has been replaced by wound treatments that are much more expensive—and may be less effective. Cost matters, and all things being equal, it’s time to promote the Unna boot once more.

Charles Mayer, MD, MPH
Seattle, Wash

As a family physician certified by the American Board of Venous and Lymphatic Disease, I would like to point out a couple of things.

First, while the authors discussed compression, they did not define what that meant. This is important, as many physicians prescribe TED hose for venous stasis ulcers, although it does not provide enough compression.

Secondly, fixing the underlying problem should be considered part of the initial treatment. Studies show that a combination of compression and intervention is the best way to ensure long-term healing of venous stasis ulcers.^1,2 I would recommend that such patients be referred to a phlebologist for evaluation. Compression alone has a poor long-term outcome for the healing of ulceration.

Lornell E. Hansen II, MD, FAAFP
Sioux Falls, SD

EVIDENCE SUMMARY

In a meta-analysis of 31 studies with 10,130 patients, researchers reported that the total rate of sexual dysfunction (SD) associated with selective serotonin reuptake inhibitors (SSRIs) was significantly higher than the placebo rate of 14.2% (TABLE).¹ The SSRIs citalopram, fluoxetine, paroxetine, and sertraline as well as the SNRI venlafaxine, had significantly greater rates (70%-80%) of reported total sexual dysfunction, including desire, arousal, and orgasm, than placebo.

Bupropion has sexual dysfunction rates comparable to placebo

Other SSRIs (fluvoxamine, escitalopram), the tricyclic antidepressant imipramine, and the SNRI duloxetine also had total SD rates significantly greater than placebo. However, the rates of dysfunction with these agents are often lower than the dysfunction rates of SSRIs such as sertraline and citalopram, and thus, may be viewed as falling into an intermediate risk category. The total SD rates for the NDRI bupropion were comparable to the placebo rate.¹

With few exceptions, all drugs associated with overall SD were associated with significant dysfunction affecting the sexual components of desire, arousal, and orgasm. The results of this meta-analysis should be interpreted with some degree of caution because methods of assessing SD varied within individual studies.

AHRQ weighs in

An Agency for Healthcare Research and Quality (AHRQ) review of antidepressants found that paroxetine, citalopram, and venlafaxine, when compared with other antidepressants (fluoxetine, fluvoxamine, nefazodone, sertraline), generally were associated with more reports of SD, specifically complaints of erectile dysfunction in men and decreased vaginal lubrication in women. 2 The number needed to treat one additional person with general sexual functioning satisfaction was 6 (95% CI, 4-9) with buproprion.²

RECOMMENDATIONS

The American College of Physicians’ clinical practice guidelines suggest that although SD is likely underreported, the NDRI bupropion has consistently shown lower rates of associated dysfunction than the SSRIs fluoxetine and sertraline.³ Conversely, the SSRI paroxetine has shown higher rates of adverse sexual events than other SSRIs, such as fluoxetine and fluvoxamine, and the serotonin reuptake inhibitor/antagonist nefazodone.³

EVIDENCE SUMMARY

In a meta-analysis of 31 studies with 10,130 patients, researchers reported that the total rate of sexual dysfunction (SD) associated with selective serotonin reuptake inhibitors (SSRIs) was significantly higher than the placebo rate of 14.2% (TABLE).¹ The SSRIs citalopram, fluoxetine, paroxetine, and sertraline as well as the SNRI venlafaxine, had significantly greater rates (70%-80%) of reported total sexual dysfunction, including desire, arousal, and orgasm, than placebo.

Bupropion has sexual dysfunction rates comparable to placebo

Other SSRIs (fluvoxamine, escitalopram), the tricyclic antidepressant imipramine, and the SNRI duloxetine also had total SD rates significantly greater than placebo. However, the rates of dysfunction with these agents are often lower than the dysfunction rates of SSRIs such as sertraline and citalopram, and thus, may be viewed as falling into an intermediate risk category. The total SD rates for the NDRI bupropion were comparable to the placebo rate.¹

With few exceptions, all drugs associated with overall SD were associated with significant dysfunction affecting the sexual components of desire, arousal, and orgasm. The results of this meta-analysis should be interpreted with some degree of caution because methods of assessing SD varied within individual studies.

AHRQ weighs in

An Agency for Healthcare Research and Quality (AHRQ) review of antidepressants found that paroxetine, citalopram, and venlafaxine, when compared with other antidepressants (fluoxetine, fluvoxamine, nefazodone, sertraline), generally were associated with more reports of SD, specifically complaints of erectile dysfunction in men and decreased vaginal lubrication in women. 2 The number needed to treat one additional person with general sexual functioning satisfaction was 6 (95% CI, 4-9) with buproprion.²

RECOMMENDATIONS

The American College of Physicians’ clinical practice guidelines suggest that although SD is likely underreported, the NDRI bupropion has consistently shown lower rates of associated dysfunction than the SSRIs fluoxetine and sertraline.³ Conversely, the SSRI paroxetine has shown higher rates of adverse sexual events than other SSRIs, such as fluoxetine and fluvoxamine, and the serotonin reuptake inhibitor/antagonist nefazodone.³

EVIDENCE SUMMARY

In a meta-analysis of 31 studies with 10,130 patients, researchers reported that the total rate of sexual dysfunction (SD) associated with selective serotonin reuptake inhibitors (SSRIs) was significantly higher than the placebo rate of 14.2% (TABLE).¹ The SSRIs citalopram, fluoxetine, paroxetine, and sertraline as well as the SNRI venlafaxine, had significantly greater rates (70%-80%) of reported total sexual dysfunction, including desire, arousal, and orgasm, than placebo.

Bupropion has sexual dysfunction rates comparable to placebo

Other SSRIs (fluvoxamine, escitalopram), the tricyclic antidepressant imipramine, and the SNRI duloxetine also had total SD rates significantly greater than placebo. However, the rates of dysfunction with these agents are often lower than the dysfunction rates of SSRIs such as sertraline and citalopram, and thus, may be viewed as falling into an intermediate risk category. The total SD rates for the NDRI bupropion were comparable to the placebo rate.¹

With few exceptions, all drugs associated with overall SD were associated with significant dysfunction affecting the sexual components of desire, arousal, and orgasm. The results of this meta-analysis should be interpreted with some degree of caution because methods of assessing SD varied within individual studies.

AHRQ weighs in

An Agency for Healthcare Research and Quality (AHRQ) review of antidepressants found that paroxetine, citalopram, and venlafaxine, when compared with other antidepressants (fluoxetine, fluvoxamine, nefazodone, sertraline), generally were associated with more reports of SD, specifically complaints of erectile dysfunction in men and decreased vaginal lubrication in women. 2 The number needed to treat one additional person with general sexual functioning satisfaction was 6 (95% CI, 4-9) with buproprion.²

RECOMMENDATIONS

The American College of Physicians’ clinical practice guidelines suggest that although SD is likely underreported, the NDRI bupropion has consistently shown lower rates of associated dysfunction than the SSRIs fluoxetine and sertraline.³ Conversely, the SSRI paroxetine has shown higher rates of adverse sexual events than other SSRIs, such as fluoxetine and fluvoxamine, and the serotonin reuptake inhibitor/antagonist nefazodone.³

Estimates suggest that about 18 million adults in the United States suffer from fecal incontinence.¹ But because the condition often goes unreported by patients and undetected by physicians, the actual prevalence is not known—and may be considerably higher.

What is known is that fecal incontinence carries a substantial socioeconomic burden. The average annual per patient cost is estimated at $4110.² But fecal incontinence also exacts a heavy personal toll, and is one of the main reasons elderly individuals are placed in nursing homes.³

But it’s not just the elderly who are affected. A recent study of women ages 45 years and older found that nearly one in 5 had an episode of fecal incontinence at least once a year, and for nearly half, the frequency was once a month or more.⁴ Less than 3 in 10 reported their symptoms to a clinician, but those who did were most likely to have confided in their primary care physician.⁵

Fortunately, recent developments—most notably, sacral nerve stimulation, a minimally invasive surgical technique with a high success rate—have changed the outlook for patients with fecal incontinence. Here’s what you need to know to help patients who suffer from this embarrassing condition achieve optimal outcomes.

Risk factors and key causes

Maintaining fecal continence involves a complex series of events, both voluntary and involuntary. Problems at various levels—stool consistency, anatomic and neurologic abnormalities, and psychological problems among them—can disrupt the process.

Those at high risk for fecal incontinence, in addition to the elderly, include patients who are mentally ill and institutionalized, individuals with neurologic disorders, patients who have had anorectal surgery, and women who have had vaginal deliveries.^6-8 Obstetric and operative injuries account for most cases of fecal incontinence.^9-10

Risks of vaginal delivery
As many as 25% of women report some degree of fecal incontinence—although often confined to loss of control of flatus—3 months after giving birth.¹¹ Stool incontinence is more frequent among women who sustained third- or fourth-degree perineal tears. Obstetrical risk factors include first vaginal birth, median episiotomy, forceps delivery, vacuum-assisted delivery, and a prolonged second stage of labor.

Asymptomatic sphincter defects. Studies in which women underwent endosonographic examination of the sphincter complex both before and after vaginal delivery have found sphincter defects in anywhere from 7% to 41% of new mothers.^12-14 It is important to note, however, that as many as 70% of those with defects detected by sonogram were asymptomatic.¹⁵ (Despite the risk of sphincter injury during vaginal delivery and evidence suggesting that the risk of fecal incontinence increases with additional deliveries after a previous perineal tear, prophylactic cesarean section is not recommended.)

Fistula surgery and postop incontinence
Fistula surgery is the primary cause of postoperative incontinence, typically resulting from inadvertent injury to either the internal or external sphincter muscle.¹⁶ Other relatively common causes of fecal incontinence are rectal prolapse, trauma, irradiation, neurologic and demyelinating disorders such as multiple sclerosis, neoplasms, stroke, infection (eg, of a perineal wound), and diabetes.¹⁷ As diagnostic modalities have improved, much of what was previously termed idiopathic incontinence has been found to have identifiable underlying pathology, such as pudendal and inferior hypogastric neuropathies.^18-20

Identifying fecal incontinence starts with a single question
As already noted, most patients with symptoms of bowel leakage do not voluntarily mention it to their physician. Many are likely to acknowledge the problem, however, if they’re specifically asked. While little has been written about how best to screen for fecal incontinence, simply adding it to the checklist on your medical intake form may be a good starting point.

Follow up with a targeted history and physical
When a patient checks fecal incontinence on a form or broaches the subject, it is important to question him or her about medical conditions that may be related. These include urinary incontinence, prolapsing tissue, diabetes, and a history of radiation, as well as childbirth. A medication history is also needed, as certain drugs—including some antacids and laxatives—have been implicated in fecal incontinence.²¹

Physical assessment should include a general neurologic exam as well as a perineal exam, to look for prolapsing tissue and evidence of scars from prior surgery or obstetrical trauma. Check the anocutaneous reflex by stroking the perianal skin. Absence of the anal wink in a younger patient is likely associated with nerve damage; in an older patient, it may simply indicate muscle weakness. Perform a digital rectal exam to assess for normal resting tone and augmentation with squeeze, regardless of the patient’s age. 

Absence of the anal wink in a younger patient is likely associated with nerve damage; in an older patient, it may simply indicate muscle weakness.

Use tools to assess the severity

Anal incontinence can be broadly characterized as complete or partial. Numerous other systems have been proposed for classifying severity, the simplest of which has the following 4 components:
A: Continent of solid, liquid, and flatus (complete continence)
B: Continent of solid and liquid, but not flatus
C: Continent of solid, but not liquid or flatus
D: Continued fecal leakage (complete incontinence).²²

Although this classification system may be helpful, it yields little information about the significance of the problem from the patient’s perspective.²³ Thus, scales that take into account both the frequency of incontinence episodes and the extent of both the mental and physical impact are used more frequently.

One of the most widely used scales is the Cleveland Clinic Fecal Incontinence Score (TABLE),²⁴ which quantifies both the frequency and type of incontinence and scores the level of severity. Fecal incontinence quality of life scales are available, as well, and include questions about the impact on the patient’s lifestyle, coping behavior, mood, and level of embarrassment.²⁵

Even without a quality of life scale, a couple of targeted questions—(eg, Are you ever afraid to go out? Do you worry about others smelling stool on you?)—will give you an idea of how great an impact fecal incontinence is having on your patient’s life. Asking patients to keep bowel diaries can also be helpful in assessing the extent of the problem and the effect of treatment.

Next steps: Start with modifiable risks

While there are numerous diagnostic tests for fecal incontinence (more about these in a bit), none is necessary for initial treatment, which starts with modifiable risks. Chief among them is smoking.

Smoking cessation. Nicotine is believed to have a direct effect on colonic transit and rectal compliance.²⁶ Thus, smoking is associated with an increased risk for fecal incontinence, independent of chronic cough or chronic obstructive pulmonary disease. Patients should be advised to quit smoking and referred to a smoking cessation program.

Dietary fiber. Diet may be a factor in fecal incontinence, as well. Ask patients to record everything they eat, and advise those with a low intake of dietary fiber to eat more fruits, vegetables, whole grains, and other high-fiber food. Recommend that they avoid caffeine and alcohol, as well.

Some medications may also affect stool form and frequency, and precipitate fecal incontinence. Common offenders, in addition to laxatives and antacids, include antibiotics, proton pump inhibitors, and senna-based colon cleansers.²⁷ Consider a switch to another drug class. A trial with a drug thought to improve bowel continence is recommended, as well.

Prescribe pharmacologic treatment
Kaolin, pectin, bulking agents, bismuth salts, anticholinergics, opium derivatives, diphenoxylate/atropine, and loperamide have all been used to treat fecal incontinence, with variable success. Loperamide, the drug most extensively studied for this purpose, has been found to increase resting anal pressure and improve anal sphincter function and continence by acting directly on the circular and longitudinal muscles of the bowel.²⁸

Amitriptyline has also been used empirically, with some success. It is believed to work by decreasing the frequency and amplitude of rectal motor complexes.²⁹ Clonidine in the form of a transdermal patch has been shown to increase the number of problem-free days and overall quality of life for patients with fecal incontinence.³⁰

Consider biofeedback
Biofeedback training is often the next step after pharmacologic treatment. It has been investigated for the treatment of fecal incontinence, and many patients—particularly if they are highly motivated—have reported improvement.³¹ Therapy generally has 3 components: exercising the external sphincter complex, training in the discrimination of rectal sensations, and developing synchrony of the internal and external sphincter responses during rectal distension.

The goal is for the patient to learn to contract the sphincter in response to small amounts of rectal distension.

But a significant time commitment on the part of the patient and sophisticated apparatus are necessary to carry out such therapy, and only a few randomized controlled trials (RCTs) have evaluated the effect. The largest RCT had 4 arms: a standard care group; standard care plus instruction on sphincter exercises; standard care with sphincter exercises and biofeedback; and standard care with sphincter exercises, biofeedback, and training at home.³²

All 4 groups had similar improvement in symptoms, raising questions about the therapeutic value of biofeedback.³² Long-term studies have found that 60% to 80% of patients will continue to have episodes of incontinence after undergoing biofeedback. A Cochrane review of RCTs concluded that there is not enough evidence to judge whether sphincter exercises and biofeedback are effective in reducing fecal incontinence.³³Long-term studies have found that 60% to 80% of patients will continue to have episodes of incontinence after undergoing biofeedback.

Still no relief? Order tests and consider surgery

For patients with fecal incontinence refractory to conservative management, more sophisticated diagnostic studies can provide invaluable information for guiding further treatment.

Endoanal ultrasound is considered the gold standard diagnostic test for fecal incontinence. It is superior to electromyography in terms of availability, patient tolerance, and ability to assess the internal anal sphincter, except in cases in which nerve injury is suspected.³⁴

Other tests sometimes used to pinpoint the cause of fecal incontinence include an enema challenge (which can differentiate between liquid and solid incontinence) and anal manometry (which can quantify anal sphincter tone). Defecography (which makes it possible to visualize the rectal emptying process) can be helpful if a diagnosis of rectal prolapse is being considered.

Magnetic resonance imaging is among the most costly diagnostic studies associated with fecal incontinence. But it is the only modality that can depict the morphology of the external sphincter and the presence of muscle atrophy—providing information that has been shown to significantly improve the likelihood of successful sphincter repair.³⁵

A wider range of surgical options

When medical therapy and biofeedback fail to produce adequate results, referral to a colorectal surgeon is appropriate. (Although conservative management is frequently unsuccessful, health plans typically require that they be attempted before surgical intervention is considered.)

Sphincteroplasty, or anterior anal sphincter repair, addresses the most common cause of fecal incontinence—and is still a common surgical procedure.³⁶ Sphincteroplasty generally has good to excellent results, providing there is sufficient muscle mass for a successful repair.^37,38

The procedure involves dissecting the sphincter complex from the surrounding anoderm, then overlapping the edges of the sphincter muscle and suturing them together. Continence has been reported nearly 80% of the time, although a longer duration of fecal incontinence and incontinence secondary to operative injury of the sphincter are risk factors for poorer outcomes.^39,40

Recent studies have called into question the durability of anterior sphincter repair. A systematic review of 16 studies reporting short- and long-term outcomes for more than 900 patients found that all but one of the studies showed a decline over time in the number of patients who were happy with the outcome.³⁹

Sacral nerve stimulation is first-line surgical treatment
Sacral nerve stimulation (SNS) is the most promising development in the treatment of fecal incontinence. In the last decade, SNS has become the first-line surgical treatment for patients for whom medical and behavioral therapy are unsuccessful.⁴⁰

A minimally invasive procedure that involves an implantable device, SNS is always preceded by an effectiveness trial in which a finder needle is percutaneously inserted into the third sacral foramen. Stimulation should result in immediate contraction of the pelvic floor and external sphincter and plantar flexion of the big toe.

The next step is the insertion of a temporary stimulator lead, which remains in place for a 2- to 3-week test of low-frequency stimulation. If significant reduction in the number of incontinence episodes during the trial period occurs, the device is inserted (See “Sacral nerve stimulation: A case study” above).

Improvement in fecal continence has been reported to be as high as 100% in some cases, with up to 75% of patients achieving complete continence.⁴¹ While the mechanism involved remains unclear, multiple studies have confirmed its effectiveness.^42,43

Posterior tibial nerve stimulation is another recent development, in which a small, thin lead is placed at the posterior tibial nerve, then connected to a temporary stimulator. Less data are available for this treatment, but a recent review summarized the findings of 8 published studies and found success rates ranging from 30% to 83%.⁴⁴

The Secca procedure—a relatively new therapy that delivers radiofrequency energy to the anal sphincter—is another option, believed to work by reducing compliance of the sphincter complex and the level of tolerable rectal distension.⁴⁵ Procedures using injectable bulking materials and fat grafting around the sphincter complex have demonstrated some promise, as well.⁴⁶

A number of other surgical modalities are available, and often effective under certain circumstances. Among them are rotational and free muscle transfers, used only in cases in which the bulk of the sphincter complex has been destroyed.^47,48 Implantable anal sphincters (made from human muscle and nerve cells) are occasionally used, as well, but frequently need to be removed because of infection.^49-51

Regardless of the type of treatment they receive, patients often do not achieve total continence. Anyone who continues to have occasional episodes of fecal incontinence or leakage should be advised to wear incontinence pads, as needed.

Consider colostomy when incontinence is severe

For patients with fecal incontinence severe enough to be disabling—often as a result of irradiation—colostomy remains a tried and true treatment. The rectum can either be left intact or a proctectomy performed in concert with ostomy creation. Most studies evaluating colostomy for the treatment of incontinence have found that it significantly improves the quality of life and that most patients say they would choose to undergo the procedure again.⁵²

Estimates suggest that about 18 million adults in the United States suffer from fecal incontinence.¹ But because the condition often goes unreported by patients and undetected by physicians, the actual prevalence is not known—and may be considerably higher.

What is known is that fecal incontinence carries a substantial socioeconomic burden. The average annual per patient cost is estimated at $4110.² But fecal incontinence also exacts a heavy personal toll, and is one of the main reasons elderly individuals are placed in nursing homes.³

But it’s not just the elderly who are affected. A recent study of women ages 45 years and older found that nearly one in 5 had an episode of fecal incontinence at least once a year, and for nearly half, the frequency was once a month or more.⁴ Less than 3 in 10 reported their symptoms to a clinician, but those who did were most likely to have confided in their primary care physician.⁵

Fortunately, recent developments—most notably, sacral nerve stimulation, a minimally invasive surgical technique with a high success rate—have changed the outlook for patients with fecal incontinence. Here’s what you need to know to help patients who suffer from this embarrassing condition achieve optimal outcomes.

Risk factors and key causes

Maintaining fecal continence involves a complex series of events, both voluntary and involuntary. Problems at various levels—stool consistency, anatomic and neurologic abnormalities, and psychological problems among them—can disrupt the process.

Those at high risk for fecal incontinence, in addition to the elderly, include patients who are mentally ill and institutionalized, individuals with neurologic disorders, patients who have had anorectal surgery, and women who have had vaginal deliveries.^6-8 Obstetric and operative injuries account for most cases of fecal incontinence.^9-10

Risks of vaginal delivery
As many as 25% of women report some degree of fecal incontinence—although often confined to loss of control of flatus—3 months after giving birth.¹¹ Stool incontinence is more frequent among women who sustained third- or fourth-degree perineal tears. Obstetrical risk factors include first vaginal birth, median episiotomy, forceps delivery, vacuum-assisted delivery, and a prolonged second stage of labor.

Asymptomatic sphincter defects. Studies in which women underwent endosonographic examination of the sphincter complex both before and after vaginal delivery have found sphincter defects in anywhere from 7% to 41% of new mothers.^12-14 It is important to note, however, that as many as 70% of those with defects detected by sonogram were asymptomatic.¹⁵ (Despite the risk of sphincter injury during vaginal delivery and evidence suggesting that the risk of fecal incontinence increases with additional deliveries after a previous perineal tear, prophylactic cesarean section is not recommended.)

Fistula surgery and postop incontinence
Fistula surgery is the primary cause of postoperative incontinence, typically resulting from inadvertent injury to either the internal or external sphincter muscle.¹⁶ Other relatively common causes of fecal incontinence are rectal prolapse, trauma, irradiation, neurologic and demyelinating disorders such as multiple sclerosis, neoplasms, stroke, infection (eg, of a perineal wound), and diabetes.¹⁷ As diagnostic modalities have improved, much of what was previously termed idiopathic incontinence has been found to have identifiable underlying pathology, such as pudendal and inferior hypogastric neuropathies.^18-20

Identifying fecal incontinence starts with a single question
As already noted, most patients with symptoms of bowel leakage do not voluntarily mention it to their physician. Many are likely to acknowledge the problem, however, if they’re specifically asked. While little has been written about how best to screen for fecal incontinence, simply adding it to the checklist on your medical intake form may be a good starting point.

Follow up with a targeted history and physical
When a patient checks fecal incontinence on a form or broaches the subject, it is important to question him or her about medical conditions that may be related. These include urinary incontinence, prolapsing tissue, diabetes, and a history of radiation, as well as childbirth. A medication history is also needed, as certain drugs—including some antacids and laxatives—have been implicated in fecal incontinence.²¹

Physical assessment should include a general neurologic exam as well as a perineal exam, to look for prolapsing tissue and evidence of scars from prior surgery or obstetrical trauma. Check the anocutaneous reflex by stroking the perianal skin. Absence of the anal wink in a younger patient is likely associated with nerve damage; in an older patient, it may simply indicate muscle weakness. Perform a digital rectal exam to assess for normal resting tone and augmentation with squeeze, regardless of the patient’s age. 

Absence of the anal wink in a younger patient is likely associated with nerve damage; in an older patient, it may simply indicate muscle weakness.

Use tools to assess the severity

Anal incontinence can be broadly characterized as complete or partial. Numerous other systems have been proposed for classifying severity, the simplest of which has the following 4 components:
A: Continent of solid, liquid, and flatus (complete continence)
B: Continent of solid and liquid, but not flatus
C: Continent of solid, but not liquid or flatus
D: Continued fecal leakage (complete incontinence).²²

Although this classification system may be helpful, it yields little information about the significance of the problem from the patient’s perspective.²³ Thus, scales that take into account both the frequency of incontinence episodes and the extent of both the mental and physical impact are used more frequently.

One of the most widely used scales is the Cleveland Clinic Fecal Incontinence Score (TABLE),²⁴ which quantifies both the frequency and type of incontinence and scores the level of severity. Fecal incontinence quality of life scales are available, as well, and include questions about the impact on the patient’s lifestyle, coping behavior, mood, and level of embarrassment.²⁵

Even without a quality of life scale, a couple of targeted questions—(eg, Are you ever afraid to go out? Do you worry about others smelling stool on you?)—will give you an idea of how great an impact fecal incontinence is having on your patient’s life. Asking patients to keep bowel diaries can also be helpful in assessing the extent of the problem and the effect of treatment.

Next steps: Start with modifiable risks

While there are numerous diagnostic tests for fecal incontinence (more about these in a bit), none is necessary for initial treatment, which starts with modifiable risks. Chief among them is smoking.

Smoking cessation. Nicotine is believed to have a direct effect on colonic transit and rectal compliance.²⁶ Thus, smoking is associated with an increased risk for fecal incontinence, independent of chronic cough or chronic obstructive pulmonary disease. Patients should be advised to quit smoking and referred to a smoking cessation program.

Dietary fiber. Diet may be a factor in fecal incontinence, as well. Ask patients to record everything they eat, and advise those with a low intake of dietary fiber to eat more fruits, vegetables, whole grains, and other high-fiber food. Recommend that they avoid caffeine and alcohol, as well.

Some medications may also affect stool form and frequency, and precipitate fecal incontinence. Common offenders, in addition to laxatives and antacids, include antibiotics, proton pump inhibitors, and senna-based colon cleansers.²⁷ Consider a switch to another drug class. A trial with a drug thought to improve bowel continence is recommended, as well.

Prescribe pharmacologic treatment
Kaolin, pectin, bulking agents, bismuth salts, anticholinergics, opium derivatives, diphenoxylate/atropine, and loperamide have all been used to treat fecal incontinence, with variable success. Loperamide, the drug most extensively studied for this purpose, has been found to increase resting anal pressure and improve anal sphincter function and continence by acting directly on the circular and longitudinal muscles of the bowel.²⁸

Amitriptyline has also been used empirically, with some success. It is believed to work by decreasing the frequency and amplitude of rectal motor complexes.²⁹ Clonidine in the form of a transdermal patch has been shown to increase the number of problem-free days and overall quality of life for patients with fecal incontinence.³⁰

Consider biofeedback
Biofeedback training is often the next step after pharmacologic treatment. It has been investigated for the treatment of fecal incontinence, and many patients—particularly if they are highly motivated—have reported improvement.³¹ Therapy generally has 3 components: exercising the external sphincter complex, training in the discrimination of rectal sensations, and developing synchrony of the internal and external sphincter responses during rectal distension.

The goal is for the patient to learn to contract the sphincter in response to small amounts of rectal distension.

But a significant time commitment on the part of the patient and sophisticated apparatus are necessary to carry out such therapy, and only a few randomized controlled trials (RCTs) have evaluated the effect. The largest RCT had 4 arms: a standard care group; standard care plus instruction on sphincter exercises; standard care with sphincter exercises and biofeedback; and standard care with sphincter exercises, biofeedback, and training at home.³²

All 4 groups had similar improvement in symptoms, raising questions about the therapeutic value of biofeedback.³² Long-term studies have found that 60% to 80% of patients will continue to have episodes of incontinence after undergoing biofeedback. A Cochrane review of RCTs concluded that there is not enough evidence to judge whether sphincter exercises and biofeedback are effective in reducing fecal incontinence.³³Long-term studies have found that 60% to 80% of patients will continue to have episodes of incontinence after undergoing biofeedback.

Still no relief? Order tests and consider surgery

For patients with fecal incontinence refractory to conservative management, more sophisticated diagnostic studies can provide invaluable information for guiding further treatment.

Endoanal ultrasound is considered the gold standard diagnostic test for fecal incontinence. It is superior to electromyography in terms of availability, patient tolerance, and ability to assess the internal anal sphincter, except in cases in which nerve injury is suspected.³⁴

Other tests sometimes used to pinpoint the cause of fecal incontinence include an enema challenge (which can differentiate between liquid and solid incontinence) and anal manometry (which can quantify anal sphincter tone). Defecography (which makes it possible to visualize the rectal emptying process) can be helpful if a diagnosis of rectal prolapse is being considered.

Magnetic resonance imaging is among the most costly diagnostic studies associated with fecal incontinence. But it is the only modality that can depict the morphology of the external sphincter and the presence of muscle atrophy—providing information that has been shown to significantly improve the likelihood of successful sphincter repair.³⁵

A wider range of surgical options

When medical therapy and biofeedback fail to produce adequate results, referral to a colorectal surgeon is appropriate. (Although conservative management is frequently unsuccessful, health plans typically require that they be attempted before surgical intervention is considered.)

Sphincteroplasty, or anterior anal sphincter repair, addresses the most common cause of fecal incontinence—and is still a common surgical procedure.³⁶ Sphincteroplasty generally has good to excellent results, providing there is sufficient muscle mass for a successful repair.^37,38

The procedure involves dissecting the sphincter complex from the surrounding anoderm, then overlapping the edges of the sphincter muscle and suturing them together. Continence has been reported nearly 80% of the time, although a longer duration of fecal incontinence and incontinence secondary to operative injury of the sphincter are risk factors for poorer outcomes.^39,40

Recent studies have called into question the durability of anterior sphincter repair. A systematic review of 16 studies reporting short- and long-term outcomes for more than 900 patients found that all but one of the studies showed a decline over time in the number of patients who were happy with the outcome.³⁹

Sacral nerve stimulation is first-line surgical treatment
Sacral nerve stimulation (SNS) is the most promising development in the treatment of fecal incontinence. In the last decade, SNS has become the first-line surgical treatment for patients for whom medical and behavioral therapy are unsuccessful.⁴⁰

A minimally invasive procedure that involves an implantable device, SNS is always preceded by an effectiveness trial in which a finder needle is percutaneously inserted into the third sacral foramen. Stimulation should result in immediate contraction of the pelvic floor and external sphincter and plantar flexion of the big toe.

The next step is the insertion of a temporary stimulator lead, which remains in place for a 2- to 3-week test of low-frequency stimulation. If significant reduction in the number of incontinence episodes during the trial period occurs, the device is inserted (See “Sacral nerve stimulation: A case study” above).

Improvement in fecal continence has been reported to be as high as 100% in some cases, with up to 75% of patients achieving complete continence.⁴¹ While the mechanism involved remains unclear, multiple studies have confirmed its effectiveness.^42,43

Posterior tibial nerve stimulation is another recent development, in which a small, thin lead is placed at the posterior tibial nerve, then connected to a temporary stimulator. Less data are available for this treatment, but a recent review summarized the findings of 8 published studies and found success rates ranging from 30% to 83%.⁴⁴

The Secca procedure—a relatively new therapy that delivers radiofrequency energy to the anal sphincter—is another option, believed to work by reducing compliance of the sphincter complex and the level of tolerable rectal distension.⁴⁵ Procedures using injectable bulking materials and fat grafting around the sphincter complex have demonstrated some promise, as well.⁴⁶

A number of other surgical modalities are available, and often effective under certain circumstances. Among them are rotational and free muscle transfers, used only in cases in which the bulk of the sphincter complex has been destroyed.^47,48 Implantable anal sphincters (made from human muscle and nerve cells) are occasionally used, as well, but frequently need to be removed because of infection.^49-51

Regardless of the type of treatment they receive, patients often do not achieve total continence. Anyone who continues to have occasional episodes of fecal incontinence or leakage should be advised to wear incontinence pads, as needed.

Consider colostomy when incontinence is severe

For patients with fecal incontinence severe enough to be disabling—often as a result of irradiation—colostomy remains a tried and true treatment. The rectum can either be left intact or a proctectomy performed in concert with ostomy creation. Most studies evaluating colostomy for the treatment of incontinence have found that it significantly improves the quality of life and that most patients say they would choose to undergo the procedure again.⁵²

Estimates suggest that about 18 million adults in the United States suffer from fecal incontinence.¹ But because the condition often goes unreported by patients and undetected by physicians, the actual prevalence is not known—and may be considerably higher.

What is known is that fecal incontinence carries a substantial socioeconomic burden. The average annual per patient cost is estimated at $4110.² But fecal incontinence also exacts a heavy personal toll, and is one of the main reasons elderly individuals are placed in nursing homes.³

But it’s not just the elderly who are affected. A recent study of women ages 45 years and older found that nearly one in 5 had an episode of fecal incontinence at least once a year, and for nearly half, the frequency was once a month or more.⁴ Less than 3 in 10 reported their symptoms to a clinician, but those who did were most likely to have confided in their primary care physician.⁵

Fortunately, recent developments—most notably, sacral nerve stimulation, a minimally invasive surgical technique with a high success rate—have changed the outlook for patients with fecal incontinence. Here’s what you need to know to help patients who suffer from this embarrassing condition achieve optimal outcomes.

Risk factors and key causes

Maintaining fecal continence involves a complex series of events, both voluntary and involuntary. Problems at various levels—stool consistency, anatomic and neurologic abnormalities, and psychological problems among them—can disrupt the process.

Those at high risk for fecal incontinence, in addition to the elderly, include patients who are mentally ill and institutionalized, individuals with neurologic disorders, patients who have had anorectal surgery, and women who have had vaginal deliveries.^6-8 Obstetric and operative injuries account for most cases of fecal incontinence.^9-10

Risks of vaginal delivery
As many as 25% of women report some degree of fecal incontinence—although often confined to loss of control of flatus—3 months after giving birth.¹¹ Stool incontinence is more frequent among women who sustained third- or fourth-degree perineal tears. Obstetrical risk factors include first vaginal birth, median episiotomy, forceps delivery, vacuum-assisted delivery, and a prolonged second stage of labor.

Asymptomatic sphincter defects. Studies in which women underwent endosonographic examination of the sphincter complex both before and after vaginal delivery have found sphincter defects in anywhere from 7% to 41% of new mothers.^12-14 It is important to note, however, that as many as 70% of those with defects detected by sonogram were asymptomatic.¹⁵ (Despite the risk of sphincter injury during vaginal delivery and evidence suggesting that the risk of fecal incontinence increases with additional deliveries after a previous perineal tear, prophylactic cesarean section is not recommended.)

Fistula surgery and postop incontinence
Fistula surgery is the primary cause of postoperative incontinence, typically resulting from inadvertent injury to either the internal or external sphincter muscle.¹⁶ Other relatively common causes of fecal incontinence are rectal prolapse, trauma, irradiation, neurologic and demyelinating disorders such as multiple sclerosis, neoplasms, stroke, infection (eg, of a perineal wound), and diabetes.¹⁷ As diagnostic modalities have improved, much of what was previously termed idiopathic incontinence has been found to have identifiable underlying pathology, such as pudendal and inferior hypogastric neuropathies.^18-20

Identifying fecal incontinence starts with a single question
As already noted, most patients with symptoms of bowel leakage do not voluntarily mention it to their physician. Many are likely to acknowledge the problem, however, if they’re specifically asked. While little has been written about how best to screen for fecal incontinence, simply adding it to the checklist on your medical intake form may be a good starting point.

Follow up with a targeted history and physical
When a patient checks fecal incontinence on a form or broaches the subject, it is important to question him or her about medical conditions that may be related. These include urinary incontinence, prolapsing tissue, diabetes, and a history of radiation, as well as childbirth. A medication history is also needed, as certain drugs—including some antacids and laxatives—have been implicated in fecal incontinence.²¹

Physical assessment should include a general neurologic exam as well as a perineal exam, to look for prolapsing tissue and evidence of scars from prior surgery or obstetrical trauma. Check the anocutaneous reflex by stroking the perianal skin. Absence of the anal wink in a younger patient is likely associated with nerve damage; in an older patient, it may simply indicate muscle weakness. Perform a digital rectal exam to assess for normal resting tone and augmentation with squeeze, regardless of the patient’s age. 

Absence of the anal wink in a younger patient is likely associated with nerve damage; in an older patient, it may simply indicate muscle weakness.

Use tools to assess the severity

Anal incontinence can be broadly characterized as complete or partial. Numerous other systems have been proposed for classifying severity, the simplest of which has the following 4 components:
A: Continent of solid, liquid, and flatus (complete continence)
B: Continent of solid and liquid, but not flatus
C: Continent of solid, but not liquid or flatus
D: Continued fecal leakage (complete incontinence).²²

Although this classification system may be helpful, it yields little information about the significance of the problem from the patient’s perspective.²³ Thus, scales that take into account both the frequency of incontinence episodes and the extent of both the mental and physical impact are used more frequently.

One of the most widely used scales is the Cleveland Clinic Fecal Incontinence Score (TABLE),²⁴ which quantifies both the frequency and type of incontinence and scores the level of severity. Fecal incontinence quality of life scales are available, as well, and include questions about the impact on the patient’s lifestyle, coping behavior, mood, and level of embarrassment.²⁵

Even without a quality of life scale, a couple of targeted questions—(eg, Are you ever afraid to go out? Do you worry about others smelling stool on you?)—will give you an idea of how great an impact fecal incontinence is having on your patient’s life. Asking patients to keep bowel diaries can also be helpful in assessing the extent of the problem and the effect of treatment.

Next steps: Start with modifiable risks

While there are numerous diagnostic tests for fecal incontinence (more about these in a bit), none is necessary for initial treatment, which starts with modifiable risks. Chief among them is smoking.

Smoking cessation. Nicotine is believed to have a direct effect on colonic transit and rectal compliance.²⁶ Thus, smoking is associated with an increased risk for fecal incontinence, independent of chronic cough or chronic obstructive pulmonary disease. Patients should be advised to quit smoking and referred to a smoking cessation program.

Dietary fiber. Diet may be a factor in fecal incontinence, as well. Ask patients to record everything they eat, and advise those with a low intake of dietary fiber to eat more fruits, vegetables, whole grains, and other high-fiber food. Recommend that they avoid caffeine and alcohol, as well.

Some medications may also affect stool form and frequency, and precipitate fecal incontinence. Common offenders, in addition to laxatives and antacids, include antibiotics, proton pump inhibitors, and senna-based colon cleansers.²⁷ Consider a switch to another drug class. A trial with a drug thought to improve bowel continence is recommended, as well.

Prescribe pharmacologic treatment
Kaolin, pectin, bulking agents, bismuth salts, anticholinergics, opium derivatives, diphenoxylate/atropine, and loperamide have all been used to treat fecal incontinence, with variable success. Loperamide, the drug most extensively studied for this purpose, has been found to increase resting anal pressure and improve anal sphincter function and continence by acting directly on the circular and longitudinal muscles of the bowel.²⁸

Amitriptyline has also been used empirically, with some success. It is believed to work by decreasing the frequency and amplitude of rectal motor complexes.²⁹ Clonidine in the form of a transdermal patch has been shown to increase the number of problem-free days and overall quality of life for patients with fecal incontinence.³⁰

Consider biofeedback
Biofeedback training is often the next step after pharmacologic treatment. It has been investigated for the treatment of fecal incontinence, and many patients—particularly if they are highly motivated—have reported improvement.³¹ Therapy generally has 3 components: exercising the external sphincter complex, training in the discrimination of rectal sensations, and developing synchrony of the internal and external sphincter responses during rectal distension.

The goal is for the patient to learn to contract the sphincter in response to small amounts of rectal distension.

But a significant time commitment on the part of the patient and sophisticated apparatus are necessary to carry out such therapy, and only a few randomized controlled trials (RCTs) have evaluated the effect. The largest RCT had 4 arms: a standard care group; standard care plus instruction on sphincter exercises; standard care with sphincter exercises and biofeedback; and standard care with sphincter exercises, biofeedback, and training at home.³²

All 4 groups had similar improvement in symptoms, raising questions about the therapeutic value of biofeedback.³² Long-term studies have found that 60% to 80% of patients will continue to have episodes of incontinence after undergoing biofeedback. A Cochrane review of RCTs concluded that there is not enough evidence to judge whether sphincter exercises and biofeedback are effective in reducing fecal incontinence.³³Long-term studies have found that 60% to 80% of patients will continue to have episodes of incontinence after undergoing biofeedback.

Still no relief? Order tests and consider surgery

For patients with fecal incontinence refractory to conservative management, more sophisticated diagnostic studies can provide invaluable information for guiding further treatment.

Endoanal ultrasound is considered the gold standard diagnostic test for fecal incontinence. It is superior to electromyography in terms of availability, patient tolerance, and ability to assess the internal anal sphincter, except in cases in which nerve injury is suspected.³⁴

Other tests sometimes used to pinpoint the cause of fecal incontinence include an enema challenge (which can differentiate between liquid and solid incontinence) and anal manometry (which can quantify anal sphincter tone). Defecography (which makes it possible to visualize the rectal emptying process) can be helpful if a diagnosis of rectal prolapse is being considered.

Magnetic resonance imaging is among the most costly diagnostic studies associated with fecal incontinence. But it is the only modality that can depict the morphology of the external sphincter and the presence of muscle atrophy—providing information that has been shown to significantly improve the likelihood of successful sphincter repair.³⁵

A wider range of surgical options

When medical therapy and biofeedback fail to produce adequate results, referral to a colorectal surgeon is appropriate. (Although conservative management is frequently unsuccessful, health plans typically require that they be attempted before surgical intervention is considered.)

Sphincteroplasty, or anterior anal sphincter repair, addresses the most common cause of fecal incontinence—and is still a common surgical procedure.³⁶ Sphincteroplasty generally has good to excellent results, providing there is sufficient muscle mass for a successful repair.^37,38

The procedure involves dissecting the sphincter complex from the surrounding anoderm, then overlapping the edges of the sphincter muscle and suturing them together. Continence has been reported nearly 80% of the time, although a longer duration of fecal incontinence and incontinence secondary to operative injury of the sphincter are risk factors for poorer outcomes.^39,40

Recent studies have called into question the durability of anterior sphincter repair. A systematic review of 16 studies reporting short- and long-term outcomes for more than 900 patients found that all but one of the studies showed a decline over time in the number of patients who were happy with the outcome.³⁹

Sacral nerve stimulation is first-line surgical treatment
Sacral nerve stimulation (SNS) is the most promising development in the treatment of fecal incontinence. In the last decade, SNS has become the first-line surgical treatment for patients for whom medical and behavioral therapy are unsuccessful.⁴⁰

A minimally invasive procedure that involves an implantable device, SNS is always preceded by an effectiveness trial in which a finder needle is percutaneously inserted into the third sacral foramen. Stimulation should result in immediate contraction of the pelvic floor and external sphincter and plantar flexion of the big toe.

The next step is the insertion of a temporary stimulator lead, which remains in place for a 2- to 3-week test of low-frequency stimulation. If significant reduction in the number of incontinence episodes during the trial period occurs, the device is inserted (See “Sacral nerve stimulation: A case study” above).

Improvement in fecal continence has been reported to be as high as 100% in some cases, with up to 75% of patients achieving complete continence.⁴¹ While the mechanism involved remains unclear, multiple studies have confirmed its effectiveness.^42,43

Posterior tibial nerve stimulation is another recent development, in which a small, thin lead is placed at the posterior tibial nerve, then connected to a temporary stimulator. Less data are available for this treatment, but a recent review summarized the findings of 8 published studies and found success rates ranging from 30% to 83%.⁴⁴

The Secca procedure—a relatively new therapy that delivers radiofrequency energy to the anal sphincter—is another option, believed to work by reducing compliance of the sphincter complex and the level of tolerable rectal distension.⁴⁵ Procedures using injectable bulking materials and fat grafting around the sphincter complex have demonstrated some promise, as well.⁴⁶

A number of other surgical modalities are available, and often effective under certain circumstances. Among them are rotational and free muscle transfers, used only in cases in which the bulk of the sphincter complex has been destroyed.^47,48 Implantable anal sphincters (made from human muscle and nerve cells) are occasionally used, as well, but frequently need to be removed because of infection.^49-51

Regardless of the type of treatment they receive, patients often do not achieve total continence. Anyone who continues to have occasional episodes of fecal incontinence or leakage should be advised to wear incontinence pads, as needed.

Consider colostomy when incontinence is severe

For patients with fecal incontinence severe enough to be disabling—often as a result of irradiation—colostomy remains a tried and true treatment. The rectum can either be left intact or a proctectomy performed in concert with ostomy creation. Most studies evaluating colostomy for the treatment of incontinence have found that it significantly improves the quality of life and that most patients say they would choose to undergo the procedure again.⁵²

A woman in her 50s underwent hysterectomy performed by a surgeon, who then assigned an ObGyn to her follow-up care. The day after surgery, the patient had severe abdominal pain with decreased blood pressure and increased heart and respiration rates. The ObGyn admitted the patient to the intensive care unit (ICU), and then designated Dr. A, the patient’s family practitioner to continue her care. Dr. A was not available, so his associate, Dr. B, took over. Over the phone, Dr. B requested pulmonary, cardiology, and infectious disease consults. In the ICU the next day, the patient suffered respiratory arrest and was intubated. When her abdomen became rigid and swollen, emergency surgery revealed that a colon perforation had allowed fecal matter to reach the abdominal cavity. The woman died the next day from complications of sepsis, peritonitis, and multiple organ failure.

ESTATE’S CLAIM None of the physicians assigned to her care ever saw the patient in the ICU. Earlier surgery could have prevented her death. The physicians involved in her care failed to communicate with each other properly.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $3.2 million Illinois settlement was reached with the hospital.

BOTH PARENTS HAD PLATELET ANTIBODIES
When a 32-year-old woman became pregnant with her third child, she sought treatment at a clinic. The mother informed the nurse practi-tioner that her two other children had been diagnosed with low platelets at birth, but they were now healthy and had no further problems.

The woman gave birth vaginally to her third child at term. The newborn had Apgar scores of 8 and 8, at 1 and 5 minutes, respectively. However, the child’s platelet level was 26 x 103/µL. The baby was transferred to another hospital the next day, where he was diagnosed with hydrocephalus and neonatal alloimmune thrombocytopenia. He suffered a massive intracranial hemorrhage, which caused severe neurologic injuries and brain damage. A shunt was placed. The child has significant cognitive deficits as well as cerebral palsy with mild developmental delays. Testing showed that each parent had a different genotype for platelet antibodies.

PARENTS’ CLAIM The parents should have been tested for platelet antibodies prior to this birth due to the family’s history. A prenatal diagnosis of neonatal alloimmune thrombocytopenia would have allowed for treatment with gamma globulin, which could have avoided the intracranial hemorrhage.

DEFENDANTS’ DEFENSE The case was settled during the trial.  

VERDICT A $4.8 million California settlement was reached.

CORD PROLAPSE NOT CARED FOR IN AMBULANCE
At 36 weeks’ gestation, a mother called an ambulance when her membranes ruptured and she noticed an umbilical cord prolapse.

The child was in a breech presentation, experienced oxygen deprivation, and sustained severe neurologic damage.

PARENTS’ CLAIM The ambulance service was negligent in its care. The ambulance service dispatcher advised the mother to stand, squat, and push before the ambulance arrived. The ambulance attendants failed to take basic actions to relieve pressure on the prolapsed umbilical cord. The ambulance did not stop at two closer hospitals, which delayed arrival for an additional 20 minutes.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $2.7 million settlement was reached, but before it was submitted to the court for approval, the child died. The defendants then sought to revoke the settlement, but the parents claimed breach of contract. The defendants claimed that the agreement was orally negotiated independent of defense counsel and was unenforceable due to the child’s death and lack of court approval. A Texas judge issued summary judgment on breach of contract and awarded $2.7 million plus $40,000 in attorney fees to the parents.    

SECOND- AND THIRD-DEGREE BURNS TO PERINEUM
A mother received an epidural injection during vaginal delivery. Six hours later, the patient asked a nurse for a warm compress to place on her perineum. The nurse heated the compress in a microwave and then applied it to the perineal area. The compress caused second- and third-degree burns to the patient’s labia and inner left thigh. She underwent surgical repair of the burned area, and, a year later, had plastic surgery.

PATIENT’S CLAIM The nurse was negligent in overheating the compress.

DEFENDANTS’ DEFENSE The hospital agreed that the nurse who heated and applied the compress had been negligent. The hospital paid all medical expenses relating to the burns, including follow-up surgeries. 

VERDICT A $190,000 Utah verdict was returned for noneconomic damages.

DOCUMENTATION MAKES A DIFFERENCE FOR OBGYN AFTER CHILD DIES
A 30-year-old physician was pregnant with her first child. Due to a low amniotic fluid index and lagging fetal growth, she saw a maternal-fetal medicine specialist, who suggested labor induction at 39 weeks.

Labor progressed slowly. After three attempts at vacuum-assisted delivery, the ObGyn recommended cesarean delivery. The parents eventually consented to cesarean delivery after another failed vacuum-assisted attempt. Although the ObGyn had recommended cesarean 2 hours earlier, surgery was not ordered on an emergent basis.

At birth, the baby’s resuscitation took more than 20 minutes. The child lost nearly one-third of her blood volume; she had a subgaleal hemorrhage. Both parties agreed that the vacuum device probably caused the bleeding.

The child had hypoxic ischemic encephalopathy and disseminated intravascular coagulation. She suffered a myocardial infarction at 3 days of age. Without electrical brain activity, life support was removed, and the child died at 5 days of age. An autopsy found possible hypereosinophilic syndrome as the concurrent cause of death.

PARENTS’ CLAIM The mother claimed she was not informed of the risks, benefits, and alternatives to vacuum extraction; she would not have consented had she known the risks. The mother, her husband, and two family members maintained that the ObGyn offered the possibility of cesarean delivery as a question, but did not insist on it. The mother claimed she wanted what was best for the baby, and never refused a cesarean. The resuscitation efforts caused eosinophilic infiltration into several organs.

PHYSICIAN’S DEFENSE The ObGyn charted that the parents were “adamant about having a vaginal delivery,” and said she told the parents what she charted. The obstetric nurse testified that the mother delayed consent because she felt vaginal delivery was imminent. The ObGyn acted properly; eosinophilia caused the baby’s death.  

VERDICT An Illinois defense verdict was returned.

HIGH BP TO BLAME FOR DEATHS OF BOTH MOTHER AND CHILD
A 23-year-old woman’s pregnancy was at high risk because of very high blood pressure (BP). At 34 weeks’ gestation, she went to a county hospital with symptoms of high BP; she was treated and discharged 3 days later. She returned to the hospital to be checked twice more within a month. The day after the third visit, she suffered a seizure and was taken to a university hospital, where emergency cesarean delivery was performed. The mother died from an aortic rupture during delivery.

The child was born with brain injuries and died at age 4 years due to neurologic complications.

ESTATE’S CLAIM The mother was not properly treated at the county hospital, resulting in both deaths; she should not have been discharged. Under monitoring, she would have undergone delivery before the aortic rupture occurred, avoiding the baby’s brain injury.

DEFENDANTS’ DEFENSE The mother was stable when released; aortic rupture is unpredictable and unpreventable, and would have occurred under any circumstances. It is highly unusual that a woman of her age would have an aortic rupture.

VERDICT A $3,062,803 California verdict was returned. The parties then settled for $1,782,000 (with the county assuming the medical lien).

NECROTIZING FASCIITIS FROM PERFORATED COLON
A woman underwent laparoscopic-assisted vaginal hysterectomy performed by her ObGyn, and was discharged after 3 days. The next day, she went to another hospital’s emergency department (ED) with abdominal distention and rigidity, severe abdominal pain, and vomiting. She had a toxic appearance, rapid pulse rate, and hypotension. In emergency surgery, several liters of dark brown, foul-smelling fluid were found in her abdomen, and feculent peritonitis and necrotizing fasciitis were diagnosed due to a perforated sigmoid colon. She required multiple hospitalizations and operations.

PATIENT’S CLAIM Perforation occur­red during hysterectomy. The ObGyn failed to recognize the injury prior to discharge. The hospital staff did not properly assess her or communicate her symptoms to the ObGyn.

DEFENDANTS’ DEFENSE There was no negligence; proper care was given.

VERDICT A $2,922,503 Florida verdict was returned, with the jury finding the ObGyn 30% at fault and the hospital 70% at fault.

FAILURE TO REACT TO FETAL DISTRESS: $15.6M
After delivery at full term, a child suffered convulsions and seizures on her second day of life. A CT scan showed brain injuries. At age 11 years, she has severe learning and developmental delays, and requires 24-hour care.

PARENTS’ CLAIM Severe decelerations with slow return to baseline occurred several times during labor and delivery. The nurse midwife failed to recognize and react to fetal distress. A cesarean delivery should have been performed instead of a vaginal delivery. The delay in delivery caused the child’s injuries.

DEFENDANTS’ DEFENSE A prenatal neurogenetic disorder caused the child’s injuries. 

VERDICT A $15.6 million Maryland verdict was returned. It will not be automatically reduced; the awarded noneconomic damages do not exceed the state cap.

LATE DELIVERY; SEVERE INJURY TO CHILD
At 40 weeks’ gestation, a woman was admitted to the hospital in labor. When the mother’s membranes were ruptured, a small amount of meconium was noted, but the fetal monitor strips were reassuring. Two hours later, the nurse and midwife noted a pattern of decelerations, but they felt the pattern was nonrepetitive and reactive. Thirty minutes later, the nurse and midwife noted decelerations to 90 bpm with pushing, but did not call a physician.

Another midwife arrived to assist the first midwife who was new to practice. The mother was given oxygen, her position was changed, and an IV fluid bolus was administered. Thirty minutes later, the nurses recognized late decelerations and called a Code White twice while the fetal heart rate continued to decelerate. After the attending physician unsuccessfully attempted vacuum extraction, an emergency cesarean delivery was performed.

The child’s Apgar scores were 2, 3, and 3, at 1, 5, and 10 minutes, respectively. The cord blood pH was 6.66, indicating severe metabolic acidosis. She developed seizures within the first few minutes of life. Imaging studies showed global hypoxic ischemic encephalopathy. The child cannot walk, talk, or sit up unsupported at age 8, and requires a G-tube. She is cortically blind and requires antiseizure medication.

PARENTS’ CLAIM The nurse, two midwives, and physician were negligent in their care of the mother and child.

DEFENDANTS’ DEFENSE The case was settled during the trial.  

VERDICT A $5 million Massachusetts settlement was reached.

WHAT CAUSED INFECTION AFTER ABORTION?
A 20-year-old woman underwent a surgical termination of pregnancy performed by an ObGyn. After discharge, the patient developed pain and other complications requiring rehospitalization and additional surgery for a pelvic infection.

PATIENT’S CLAIM Complications were due to a uterine perforation that spontaneously sealed before it could be detected. The ObGyn was negligent in the performance of the elective abortion. The patient has a large scar on her abdomen because of the additional operation.

PHYSICIAN’S DEFENSE Perforation of the uterus is a known complication of the procedure. However, no perforation occurred; it was not found on imaging, and spontaneous sealing of a perforation cannot occur. The patient’s complications were due to a subclinical infection that was activated by the surgery.  

VERDICT A New York defense verdict was returned.

We want to hear from you. Tell us what you think!

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

A woman in her 50s underwent hysterectomy performed by a surgeon, who then assigned an ObGyn to her follow-up care. The day after surgery, the patient had severe abdominal pain with decreased blood pressure and increased heart and respiration rates. The ObGyn admitted the patient to the intensive care unit (ICU), and then designated Dr. A, the patient’s family practitioner to continue her care. Dr. A was not available, so his associate, Dr. B, took over. Over the phone, Dr. B requested pulmonary, cardiology, and infectious disease consults. In the ICU the next day, the patient suffered respiratory arrest and was intubated. When her abdomen became rigid and swollen, emergency surgery revealed that a colon perforation had allowed fecal matter to reach the abdominal cavity. The woman died the next day from complications of sepsis, peritonitis, and multiple organ failure.

ESTATE’S CLAIM None of the physicians assigned to her care ever saw the patient in the ICU. Earlier surgery could have prevented her death. The physicians involved in her care failed to communicate with each other properly.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $3.2 million Illinois settlement was reached with the hospital.

BOTH PARENTS HAD PLATELET ANTIBODIES
When a 32-year-old woman became pregnant with her third child, she sought treatment at a clinic. The mother informed the nurse practi-tioner that her two other children had been diagnosed with low platelets at birth, but they were now healthy and had no further problems.

The woman gave birth vaginally to her third child at term. The newborn had Apgar scores of 8 and 8, at 1 and 5 minutes, respectively. However, the child’s platelet level was 26 x 103/µL. The baby was transferred to another hospital the next day, where he was diagnosed with hydrocephalus and neonatal alloimmune thrombocytopenia. He suffered a massive intracranial hemorrhage, which caused severe neurologic injuries and brain damage. A shunt was placed. The child has significant cognitive deficits as well as cerebral palsy with mild developmental delays. Testing showed that each parent had a different genotype for platelet antibodies.

PARENTS’ CLAIM The parents should have been tested for platelet antibodies prior to this birth due to the family’s history. A prenatal diagnosis of neonatal alloimmune thrombocytopenia would have allowed for treatment with gamma globulin, which could have avoided the intracranial hemorrhage.

DEFENDANTS’ DEFENSE The case was settled during the trial.  

VERDICT A $4.8 million California settlement was reached.

CORD PROLAPSE NOT CARED FOR IN AMBULANCE
At 36 weeks’ gestation, a mother called an ambulance when her membranes ruptured and she noticed an umbilical cord prolapse.

The child was in a breech presentation, experienced oxygen deprivation, and sustained severe neurologic damage.

PARENTS’ CLAIM The ambulance service was negligent in its care. The ambulance service dispatcher advised the mother to stand, squat, and push before the ambulance arrived. The ambulance attendants failed to take basic actions to relieve pressure on the prolapsed umbilical cord. The ambulance did not stop at two closer hospitals, which delayed arrival for an additional 20 minutes.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $2.7 million settlement was reached, but before it was submitted to the court for approval, the child died. The defendants then sought to revoke the settlement, but the parents claimed breach of contract. The defendants claimed that the agreement was orally negotiated independent of defense counsel and was unenforceable due to the child’s death and lack of court approval. A Texas judge issued summary judgment on breach of contract and awarded $2.7 million plus $40,000 in attorney fees to the parents.    

SECOND- AND THIRD-DEGREE BURNS TO PERINEUM
A mother received an epidural injection during vaginal delivery. Six hours later, the patient asked a nurse for a warm compress to place on her perineum. The nurse heated the compress in a microwave and then applied it to the perineal area. The compress caused second- and third-degree burns to the patient’s labia and inner left thigh. She underwent surgical repair of the burned area, and, a year later, had plastic surgery.

PATIENT’S CLAIM The nurse was negligent in overheating the compress.

DEFENDANTS’ DEFENSE The hospital agreed that the nurse who heated and applied the compress had been negligent. The hospital paid all medical expenses relating to the burns, including follow-up surgeries. 

VERDICT A $190,000 Utah verdict was returned for noneconomic damages.

DOCUMENTATION MAKES A DIFFERENCE FOR OBGYN AFTER CHILD DIES
A 30-year-old physician was pregnant with her first child. Due to a low amniotic fluid index and lagging fetal growth, she saw a maternal-fetal medicine specialist, who suggested labor induction at 39 weeks.

Labor progressed slowly. After three attempts at vacuum-assisted delivery, the ObGyn recommended cesarean delivery. The parents eventually consented to cesarean delivery after another failed vacuum-assisted attempt. Although the ObGyn had recommended cesarean 2 hours earlier, surgery was not ordered on an emergent basis.

At birth, the baby’s resuscitation took more than 20 minutes. The child lost nearly one-third of her blood volume; she had a subgaleal hemorrhage. Both parties agreed that the vacuum device probably caused the bleeding.

The child had hypoxic ischemic encephalopathy and disseminated intravascular coagulation. She suffered a myocardial infarction at 3 days of age. Without electrical brain activity, life support was removed, and the child died at 5 days of age. An autopsy found possible hypereosinophilic syndrome as the concurrent cause of death.

PARENTS’ CLAIM The mother claimed she was not informed of the risks, benefits, and alternatives to vacuum extraction; she would not have consented had she known the risks. The mother, her husband, and two family members maintained that the ObGyn offered the possibility of cesarean delivery as a question, but did not insist on it. The mother claimed she wanted what was best for the baby, and never refused a cesarean. The resuscitation efforts caused eosinophilic infiltration into several organs.

PHYSICIAN’S DEFENSE The ObGyn charted that the parents were “adamant about having a vaginal delivery,” and said she told the parents what she charted. The obstetric nurse testified that the mother delayed consent because she felt vaginal delivery was imminent. The ObGyn acted properly; eosinophilia caused the baby’s death.  

VERDICT An Illinois defense verdict was returned.

HIGH BP TO BLAME FOR DEATHS OF BOTH MOTHER AND CHILD
A 23-year-old woman’s pregnancy was at high risk because of very high blood pressure (BP). At 34 weeks’ gestation, she went to a county hospital with symptoms of high BP; she was treated and discharged 3 days later. She returned to the hospital to be checked twice more within a month. The day after the third visit, she suffered a seizure and was taken to a university hospital, where emergency cesarean delivery was performed. The mother died from an aortic rupture during delivery.

The child was born with brain injuries and died at age 4 years due to neurologic complications.

ESTATE’S CLAIM The mother was not properly treated at the county hospital, resulting in both deaths; she should not have been discharged. Under monitoring, she would have undergone delivery before the aortic rupture occurred, avoiding the baby’s brain injury.

DEFENDANTS’ DEFENSE The mother was stable when released; aortic rupture is unpredictable and unpreventable, and would have occurred under any circumstances. It is highly unusual that a woman of her age would have an aortic rupture.

VERDICT A $3,062,803 California verdict was returned. The parties then settled for $1,782,000 (with the county assuming the medical lien).

NECROTIZING FASCIITIS FROM PERFORATED COLON
A woman underwent laparoscopic-assisted vaginal hysterectomy performed by her ObGyn, and was discharged after 3 days. The next day, she went to another hospital’s emergency department (ED) with abdominal distention and rigidity, severe abdominal pain, and vomiting. She had a toxic appearance, rapid pulse rate, and hypotension. In emergency surgery, several liters of dark brown, foul-smelling fluid were found in her abdomen, and feculent peritonitis and necrotizing fasciitis were diagnosed due to a perforated sigmoid colon. She required multiple hospitalizations and operations.

PATIENT’S CLAIM Perforation occur­red during hysterectomy. The ObGyn failed to recognize the injury prior to discharge. The hospital staff did not properly assess her or communicate her symptoms to the ObGyn.

DEFENDANTS’ DEFENSE There was no negligence; proper care was given.

VERDICT A $2,922,503 Florida verdict was returned, with the jury finding the ObGyn 30% at fault and the hospital 70% at fault.

FAILURE TO REACT TO FETAL DISTRESS: $15.6M
After delivery at full term, a child suffered convulsions and seizures on her second day of life. A CT scan showed brain injuries. At age 11 years, she has severe learning and developmental delays, and requires 24-hour care.

PARENTS’ CLAIM Severe decelerations with slow return to baseline occurred several times during labor and delivery. The nurse midwife failed to recognize and react to fetal distress. A cesarean delivery should have been performed instead of a vaginal delivery. The delay in delivery caused the child’s injuries.

DEFENDANTS’ DEFENSE A prenatal neurogenetic disorder caused the child’s injuries. 

VERDICT A $15.6 million Maryland verdict was returned. It will not be automatically reduced; the awarded noneconomic damages do not exceed the state cap.

LATE DELIVERY; SEVERE INJURY TO CHILD
At 40 weeks’ gestation, a woman was admitted to the hospital in labor. When the mother’s membranes were ruptured, a small amount of meconium was noted, but the fetal monitor strips were reassuring. Two hours later, the nurse and midwife noted a pattern of decelerations, but they felt the pattern was nonrepetitive and reactive. Thirty minutes later, the nurse and midwife noted decelerations to 90 bpm with pushing, but did not call a physician.

Another midwife arrived to assist the first midwife who was new to practice. The mother was given oxygen, her position was changed, and an IV fluid bolus was administered. Thirty minutes later, the nurses recognized late decelerations and called a Code White twice while the fetal heart rate continued to decelerate. After the attending physician unsuccessfully attempted vacuum extraction, an emergency cesarean delivery was performed.

The child’s Apgar scores were 2, 3, and 3, at 1, 5, and 10 minutes, respectively. The cord blood pH was 6.66, indicating severe metabolic acidosis. She developed seizures within the first few minutes of life. Imaging studies showed global hypoxic ischemic encephalopathy. The child cannot walk, talk, or sit up unsupported at age 8, and requires a G-tube. She is cortically blind and requires antiseizure medication.

PARENTS’ CLAIM The nurse, two midwives, and physician were negligent in their care of the mother and child.

DEFENDANTS’ DEFENSE The case was settled during the trial.  

VERDICT A $5 million Massachusetts settlement was reached.

WHAT CAUSED INFECTION AFTER ABORTION?
A 20-year-old woman underwent a surgical termination of pregnancy performed by an ObGyn. After discharge, the patient developed pain and other complications requiring rehospitalization and additional surgery for a pelvic infection.

PATIENT’S CLAIM Complications were due to a uterine perforation that spontaneously sealed before it could be detected. The ObGyn was negligent in the performance of the elective abortion. The patient has a large scar on her abdomen because of the additional operation.

PHYSICIAN’S DEFENSE Perforation of the uterus is a known complication of the procedure. However, no perforation occurred; it was not found on imaging, and spontaneous sealing of a perforation cannot occur. The patient’s complications were due to a subclinical infection that was activated by the surgery.  

VERDICT A New York defense verdict was returned.

We want to hear from you. Tell us what you think!

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

A woman in her 50s underwent hysterectomy performed by a surgeon, who then assigned an ObGyn to her follow-up care. The day after surgery, the patient had severe abdominal pain with decreased blood pressure and increased heart and respiration rates. The ObGyn admitted the patient to the intensive care unit (ICU), and then designated Dr. A, the patient’s family practitioner to continue her care. Dr. A was not available, so his associate, Dr. B, took over. Over the phone, Dr. B requested pulmonary, cardiology, and infectious disease consults. In the ICU the next day, the patient suffered respiratory arrest and was intubated. When her abdomen became rigid and swollen, emergency surgery revealed that a colon perforation had allowed fecal matter to reach the abdominal cavity. The woman died the next day from complications of sepsis, peritonitis, and multiple organ failure.

ESTATE’S CLAIM None of the physicians assigned to her care ever saw the patient in the ICU. Earlier surgery could have prevented her death. The physicians involved in her care failed to communicate with each other properly.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $3.2 million Illinois settlement was reached with the hospital.

BOTH PARENTS HAD PLATELET ANTIBODIES
When a 32-year-old woman became pregnant with her third child, she sought treatment at a clinic. The mother informed the nurse practi-tioner that her two other children had been diagnosed with low platelets at birth, but they were now healthy and had no further problems.

The woman gave birth vaginally to her third child at term. The newborn had Apgar scores of 8 and 8, at 1 and 5 minutes, respectively. However, the child’s platelet level was 26 x 103/µL. The baby was transferred to another hospital the next day, where he was diagnosed with hydrocephalus and neonatal alloimmune thrombocytopenia. He suffered a massive intracranial hemorrhage, which caused severe neurologic injuries and brain damage. A shunt was placed. The child has significant cognitive deficits as well as cerebral palsy with mild developmental delays. Testing showed that each parent had a different genotype for platelet antibodies.

PARENTS’ CLAIM The parents should have been tested for platelet antibodies prior to this birth due to the family’s history. A prenatal diagnosis of neonatal alloimmune thrombocytopenia would have allowed for treatment with gamma globulin, which could have avoided the intracranial hemorrhage.

DEFENDANTS’ DEFENSE The case was settled during the trial.  

VERDICT A $4.8 million California settlement was reached.

CORD PROLAPSE NOT CARED FOR IN AMBULANCE
At 36 weeks’ gestation, a mother called an ambulance when her membranes ruptured and she noticed an umbilical cord prolapse.

The child was in a breech presentation, experienced oxygen deprivation, and sustained severe neurologic damage.

PARENTS’ CLAIM The ambulance service was negligent in its care. The ambulance service dispatcher advised the mother to stand, squat, and push before the ambulance arrived. The ambulance attendants failed to take basic actions to relieve pressure on the prolapsed umbilical cord. The ambulance did not stop at two closer hospitals, which delayed arrival for an additional 20 minutes.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $2.7 million settlement was reached, but before it was submitted to the court for approval, the child died. The defendants then sought to revoke the settlement, but the parents claimed breach of contract. The defendants claimed that the agreement was orally negotiated independent of defense counsel and was unenforceable due to the child’s death and lack of court approval. A Texas judge issued summary judgment on breach of contract and awarded $2.7 million plus $40,000 in attorney fees to the parents.    

SECOND- AND THIRD-DEGREE BURNS TO PERINEUM
A mother received an epidural injection during vaginal delivery. Six hours later, the patient asked a nurse for a warm compress to place on her perineum. The nurse heated the compress in a microwave and then applied it to the perineal area. The compress caused second- and third-degree burns to the patient’s labia and inner left thigh. She underwent surgical repair of the burned area, and, a year later, had plastic surgery.

PATIENT’S CLAIM The nurse was negligent in overheating the compress.

DEFENDANTS’ DEFENSE The hospital agreed that the nurse who heated and applied the compress had been negligent. The hospital paid all medical expenses relating to the burns, including follow-up surgeries. 

VERDICT A $190,000 Utah verdict was returned for noneconomic damages.

DOCUMENTATION MAKES A DIFFERENCE FOR OBGYN AFTER CHILD DIES
A 30-year-old physician was pregnant with her first child. Due to a low amniotic fluid index and lagging fetal growth, she saw a maternal-fetal medicine specialist, who suggested labor induction at 39 weeks.

Labor progressed slowly. After three attempts at vacuum-assisted delivery, the ObGyn recommended cesarean delivery. The parents eventually consented to cesarean delivery after another failed vacuum-assisted attempt. Although the ObGyn had recommended cesarean 2 hours earlier, surgery was not ordered on an emergent basis.

At birth, the baby’s resuscitation took more than 20 minutes. The child lost nearly one-third of her blood volume; she had a subgaleal hemorrhage. Both parties agreed that the vacuum device probably caused the bleeding.

The child had hypoxic ischemic encephalopathy and disseminated intravascular coagulation. She suffered a myocardial infarction at 3 days of age. Without electrical brain activity, life support was removed, and the child died at 5 days of age. An autopsy found possible hypereosinophilic syndrome as the concurrent cause of death.

PARENTS’ CLAIM The mother claimed she was not informed of the risks, benefits, and alternatives to vacuum extraction; she would not have consented had she known the risks. The mother, her husband, and two family members maintained that the ObGyn offered the possibility of cesarean delivery as a question, but did not insist on it. The mother claimed she wanted what was best for the baby, and never refused a cesarean. The resuscitation efforts caused eosinophilic infiltration into several organs.

PHYSICIAN’S DEFENSE The ObGyn charted that the parents were “adamant about having a vaginal delivery,” and said she told the parents what she charted. The obstetric nurse testified that the mother delayed consent because she felt vaginal delivery was imminent. The ObGyn acted properly; eosinophilia caused the baby’s death.  

VERDICT An Illinois defense verdict was returned.

HIGH BP TO BLAME FOR DEATHS OF BOTH MOTHER AND CHILD
A 23-year-old woman’s pregnancy was at high risk because of very high blood pressure (BP). At 34 weeks’ gestation, she went to a county hospital with symptoms of high BP; she was treated and discharged 3 days later. She returned to the hospital to be checked twice more within a month. The day after the third visit, she suffered a seizure and was taken to a university hospital, where emergency cesarean delivery was performed. The mother died from an aortic rupture during delivery.

The child was born with brain injuries and died at age 4 years due to neurologic complications.

ESTATE’S CLAIM The mother was not properly treated at the county hospital, resulting in both deaths; she should not have been discharged. Under monitoring, she would have undergone delivery before the aortic rupture occurred, avoiding the baby’s brain injury.

DEFENDANTS’ DEFENSE The mother was stable when released; aortic rupture is unpredictable and unpreventable, and would have occurred under any circumstances. It is highly unusual that a woman of her age would have an aortic rupture.

VERDICT A $3,062,803 California verdict was returned. The parties then settled for $1,782,000 (with the county assuming the medical lien).

NECROTIZING FASCIITIS FROM PERFORATED COLON
A woman underwent laparoscopic-assisted vaginal hysterectomy performed by her ObGyn, and was discharged after 3 days. The next day, she went to another hospital’s emergency department (ED) with abdominal distention and rigidity, severe abdominal pain, and vomiting. She had a toxic appearance, rapid pulse rate, and hypotension. In emergency surgery, several liters of dark brown, foul-smelling fluid were found in her abdomen, and feculent peritonitis and necrotizing fasciitis were diagnosed due to a perforated sigmoid colon. She required multiple hospitalizations and operations.

PATIENT’S CLAIM Perforation occur­red during hysterectomy. The ObGyn failed to recognize the injury prior to discharge. The hospital staff did not properly assess her or communicate her symptoms to the ObGyn.

DEFENDANTS’ DEFENSE There was no negligence; proper care was given.

VERDICT A $2,922,503 Florida verdict was returned, with the jury finding the ObGyn 30% at fault and the hospital 70% at fault.

FAILURE TO REACT TO FETAL DISTRESS: $15.6M
After delivery at full term, a child suffered convulsions and seizures on her second day of life. A CT scan showed brain injuries. At age 11 years, she has severe learning and developmental delays, and requires 24-hour care.

PARENTS’ CLAIM Severe decelerations with slow return to baseline occurred several times during labor and delivery. The nurse midwife failed to recognize and react to fetal distress. A cesarean delivery should have been performed instead of a vaginal delivery. The delay in delivery caused the child’s injuries.

DEFENDANTS’ DEFENSE A prenatal neurogenetic disorder caused the child’s injuries. 

VERDICT A $15.6 million Maryland verdict was returned. It will not be automatically reduced; the awarded noneconomic damages do not exceed the state cap.

LATE DELIVERY; SEVERE INJURY TO CHILD
At 40 weeks’ gestation, a woman was admitted to the hospital in labor. When the mother’s membranes were ruptured, a small amount of meconium was noted, but the fetal monitor strips were reassuring. Two hours later, the nurse and midwife noted a pattern of decelerations, but they felt the pattern was nonrepetitive and reactive. Thirty minutes later, the nurse and midwife noted decelerations to 90 bpm with pushing, but did not call a physician.

Another midwife arrived to assist the first midwife who was new to practice. The mother was given oxygen, her position was changed, and an IV fluid bolus was administered. Thirty minutes later, the nurses recognized late decelerations and called a Code White twice while the fetal heart rate continued to decelerate. After the attending physician unsuccessfully attempted vacuum extraction, an emergency cesarean delivery was performed.

The child’s Apgar scores were 2, 3, and 3, at 1, 5, and 10 minutes, respectively. The cord blood pH was 6.66, indicating severe metabolic acidosis. She developed seizures within the first few minutes of life. Imaging studies showed global hypoxic ischemic encephalopathy. The child cannot walk, talk, or sit up unsupported at age 8, and requires a G-tube. She is cortically blind and requires antiseizure medication.

PARENTS’ CLAIM The nurse, two midwives, and physician were negligent in their care of the mother and child.

DEFENDANTS’ DEFENSE The case was settled during the trial.  

VERDICT A $5 million Massachusetts settlement was reached.

WHAT CAUSED INFECTION AFTER ABORTION?
A 20-year-old woman underwent a surgical termination of pregnancy performed by an ObGyn. After discharge, the patient developed pain and other complications requiring rehospitalization and additional surgery for a pelvic infection.

PATIENT’S CLAIM Complications were due to a uterine perforation that spontaneously sealed before it could be detected. The ObGyn was negligent in the performance of the elective abortion. The patient has a large scar on her abdomen because of the additional operation.

PHYSICIAN’S DEFENSE Perforation of the uterus is a known complication of the procedure. However, no perforation occurred; it was not found on imaging, and spontaneous sealing of a perforation cannot occur. The patient’s complications were due to a subclinical infection that was activated by the surgery.  

VERDICT A New York defense verdict was returned.

We want to hear from you. Tell us what you think!

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Every morning before I leave for work, I kiss my three children goodbye and tell them, “I love you. Make good choices today.”

This has become my mantra—so much so that, on her way out the door to join her friends at the movies recently, my daughter turned to me and said, “I know, Dad. I know. I’ll make good decisions tonight.”

And what decision is more important than where to deliver your child and who to have in attendance at the birth?

It is said that the passage from the uterus to the outside world that each one of us was forced to negotiate at birth is the most treacherous journey we will ever undertake. Any unnecessary delay or complication can have profound, lifelong consequences.

There is no question that the past few centuries have seen a significant “medicalization” of childbirth, including the relocation of deliveries from the community to a hospital setting, the introduction of male obstetricians, the unfortunate marginalization of midwives and support personnel (doulas), the development of uterotonic drugs, and the evolution of operative vaginal (forceps, vacuum) and cesarean deliveries.

Many of the practices initially introduced by obstetric care providers (including multiple vaginal examinations in labor, induction of labor for a large baby, and active management of labor protocols) have since been shown to be unhelpful in improving pregnancy outcomes, and some practices (such as episiotomy) have even been shown to be harmful.

Related article: Difficult fetal extraction at cesarean delivery: What should you do? Robert L. Barbieri, MD (Editorial, January 2012)

In the midst of this confusion, the one voice that has been lost is that of the patient herself.

Whose birth is it anyway?
The American College of Obstetricians and Gynecologists (ACOG), the American Academy of Pediatrics (AAP), and the American College of Nurse-Midwives (ACNM) all agree that patient autonomy is paramount, and that the final decision of where to deliver and who to have in attendance should be made by the patient herself, ideally in conjunction with her family and her obstetric care provider.^1–3 But an informed decision is only as good as the available data. Regrettably, the literature on how planned home birth compares with hospital delivery in terms of pregnancy outcomes in the United States are sparse.

Related article: Lay midwives the the ObGyn: Is collaboration risky? Lucia DiVenere, MA (May 2012)

How safe is home birth in the United States?
Cheng and colleagues attempt to answer this question by reviewing newborn and maternal outcomes among planned home births versus hospital deliveries in a contemporary low-risk birth cohort. Their retrospective study included low-risk women at term with a singleton vertex live birth in 2008 in 27 of the 50 states using information from the Vital Statistics Natality Data provided by the Centers for Disease Control and Prevention.

Of these 2,081,753 women, 0.58% (n = 12,039) had planned home births, and the remainder delivered in a hospital setting. Women who had an “accidental” (unintended) home birth or who delivered in a freestanding birthing center were excluded. The primary outcome was the risk of a 5-minute Apgar score less than 4. Secondary outcomes included the risk of a 5-minute Apgar score less than 7, assisted ventilation for more than 6 hours, neonatal seizures, admission to the NICU, and a series of maternal outcome measures.

Besides the outcomes listed previously (top of page 24), women with a planned home birth had fewer obstetric interventions, including operative vaginal delivery and labor induction or augmentation. They also were less likely to be given antibiotics during labor (although the authors did not distinguish between antibiotics administered for prophylaxis against group B strep or surgical-site infection versus antibiotics to treat infections such as urinary tract infections or chorioamnionitis).

Of special interest is the fact that neither a prior vaginal delivery (multiparity) nor the absence of a prior cesarean delivery was protective against these adverse events.

The women at highest risk of an adverse event were those who delivered at home under the supervision of “other midwives.” Although these providers were not well defined, this term typically refers to community-based lay midwives whose only “training” consists of an unofficial apprenticeship of variable length. Despite the absence of formal training, the lack of certification and standardization of care, and the existence of legislation in many states banning their activity, such lay midwives continue to encourage and support home birth for both low- and high-risk women in the United States.

Related article: Update on Obstetrics John T. Repke, MD, and Jaimey M. Pauli, MD (January 2012)

Limitations of the study design
Although this dataset contains more than 2 million births, it includes only low-risk women at term and, therefore, is underpowered to measure outcomes such as fetal or neonatal death or birth injuries.

No data were presented on a number of important variables and outcome measures, such as the rate of or indications for cesarean delivery, the mode and frequency of intrapartum fetal monitoring, birth weight, intrapartum complications (uterine rupture, postpartum hemorrhage), blood transfusions, and infectious morbidity. The study also lacks long-term follow-up data on the infants.

That said, the study was well designed and very well written, and many of the limitations listed above are inherent in all retrospective cohort studies.

Putting these findings in context
These data are not novel, but they are remarkably consistent with other publications that have explored pregnancy outcomes in planned home birth versus hospital delivery from the Netherlands, the United Kingdom, Australia, and the United States, all of which show a higher rate of neonatal complications with planned home birth [see Reference 4 for review].⁴

Moreover, it is likely that the data in the current report significantly underestimate the risks of planned home birth for two reasons:

• Attempted home births that ended in transfer and, ultimately, delivery in a hospital setting (presumably for some unforeseen event such as excessive hemorrhage or uterine rupture or cord prolapse or nonreassuring fetal testing) were classified as hospital births.
• Apgar scores at 5 minutes are assigned by the attending care provider, and there is no way to independently verify their accuracy. Because of their limited training and/or concern about efforts to limit the scope of their practice, “other midwives” may be inclined to assign more favorable Apgar scores.

Who is choosing to deliver at home?
The proportion of US women who delivered outside the hospital setting increased by 29% between 2004 and 2009,⁵ although home births still constitute a minority of low-risk births (0.58% in the current study).

Related Article: Why are well-educated women more likely to choose home birth? Errol R. Norwitz, MD, PhD (Audiocast, November 2013)

One of the more interesting questions raised by this publication is the issue of who is choosing to deliver at home. In this cohort, women who planned home birth were more likely to be older, married, multiparous, white, and well educated. These aren’t exactly the women you would expect to gamble with the lives of their unborn offspring. So why are they choosing to deliver at home?

It could be that they are not well informed about the risks. Alternatively, they may have concluded that, although the relative risk of an adverse event is significantly higher with home birth, the absolute risk is low and acceptable to them. Or it could be that they are frustrated by the lack of autonomy afforded to them in the decisions surrounding antenatal care and the birthing process.

In recent years, more women are asking for minimally invasive births that are physically, emotionally, and socially supported. As hospital-based obstetric care providers, we do not always respect or meet these expectations. We can and should do better.

Women should not have to choose between a good birth experience and medical safety, between social support and hospital resources, between a sense of autonomy and access to life-saving interventions. Although every effort should be taken to make the birthing experience a positive one for the mother and her family as a whole, it should not be done at the expense of safety. I have yet to hear an asphyxiated and brain-damaged child thank his mother’s obstetric care provider for allowing a wonderful birth experience.

What this evidence means for practice
Even in countries where home births are integrated fully into the medical care system and attended by trained and certified nurse-midwives, they are associated with increased risks, including a twofold to threefold increase in the odds of neonatal death.4 In the US, where no such integration exists, home births are dangerous.

Maternity care has come a long way since the 17th Century, when a woman had a 1 in 6 chance of dying in childbirth and only one of every five children lived to enjoy a first birthday. It is appropriate in this era of Obamacare and cost containment that we explore alternative methods. The option of a safe home delivery may well be part of the solution, as it is for many European countries--but until we can be assured that such an approach is safe for both mothers and infants, let's keep home delivery where it belongs...for pizza!

--Errol R. Norwitz, MD, PHD

We want to hear from you! Tell us what you think.

Every morning before I leave for work, I kiss my three children goodbye and tell them, “I love you. Make good choices today.”

This has become my mantra—so much so that, on her way out the door to join her friends at the movies recently, my daughter turned to me and said, “I know, Dad. I know. I’ll make good decisions tonight.”

And what decision is more important than where to deliver your child and who to have in attendance at the birth?

It is said that the passage from the uterus to the outside world that each one of us was forced to negotiate at birth is the most treacherous journey we will ever undertake. Any unnecessary delay or complication can have profound, lifelong consequences.

There is no question that the past few centuries have seen a significant “medicalization” of childbirth, including the relocation of deliveries from the community to a hospital setting, the introduction of male obstetricians, the unfortunate marginalization of midwives and support personnel (doulas), the development of uterotonic drugs, and the evolution of operative vaginal (forceps, vacuum) and cesarean deliveries.

Many of the practices initially introduced by obstetric care providers (including multiple vaginal examinations in labor, induction of labor for a large baby, and active management of labor protocols) have since been shown to be unhelpful in improving pregnancy outcomes, and some practices (such as episiotomy) have even been shown to be harmful.

Related article: Difficult fetal extraction at cesarean delivery: What should you do? Robert L. Barbieri, MD (Editorial, January 2012)

In the midst of this confusion, the one voice that has been lost is that of the patient herself.

Whose birth is it anyway?
The American College of Obstetricians and Gynecologists (ACOG), the American Academy of Pediatrics (AAP), and the American College of Nurse-Midwives (ACNM) all agree that patient autonomy is paramount, and that the final decision of where to deliver and who to have in attendance should be made by the patient herself, ideally in conjunction with her family and her obstetric care provider.^1–3 But an informed decision is only as good as the available data. Regrettably, the literature on how planned home birth compares with hospital delivery in terms of pregnancy outcomes in the United States are sparse.

Related article: Lay midwives the the ObGyn: Is collaboration risky? Lucia DiVenere, MA (May 2012)

How safe is home birth in the United States?
Cheng and colleagues attempt to answer this question by reviewing newborn and maternal outcomes among planned home births versus hospital deliveries in a contemporary low-risk birth cohort. Their retrospective study included low-risk women at term with a singleton vertex live birth in 2008 in 27 of the 50 states using information from the Vital Statistics Natality Data provided by the Centers for Disease Control and Prevention.

Of these 2,081,753 women, 0.58% (n = 12,039) had planned home births, and the remainder delivered in a hospital setting. Women who had an “accidental” (unintended) home birth or who delivered in a freestanding birthing center were excluded. The primary outcome was the risk of a 5-minute Apgar score less than 4. Secondary outcomes included the risk of a 5-minute Apgar score less than 7, assisted ventilation for more than 6 hours, neonatal seizures, admission to the NICU, and a series of maternal outcome measures.

Besides the outcomes listed previously (top of page 24), women with a planned home birth had fewer obstetric interventions, including operative vaginal delivery and labor induction or augmentation. They also were less likely to be given antibiotics during labor (although the authors did not distinguish between antibiotics administered for prophylaxis against group B strep or surgical-site infection versus antibiotics to treat infections such as urinary tract infections or chorioamnionitis).

Of special interest is the fact that neither a prior vaginal delivery (multiparity) nor the absence of a prior cesarean delivery was protective against these adverse events.

The women at highest risk of an adverse event were those who delivered at home under the supervision of “other midwives.” Although these providers were not well defined, this term typically refers to community-based lay midwives whose only “training” consists of an unofficial apprenticeship of variable length. Despite the absence of formal training, the lack of certification and standardization of care, and the existence of legislation in many states banning their activity, such lay midwives continue to encourage and support home birth for both low- and high-risk women in the United States.

Related article: Update on Obstetrics John T. Repke, MD, and Jaimey M. Pauli, MD (January 2012)

Limitations of the study design
Although this dataset contains more than 2 million births, it includes only low-risk women at term and, therefore, is underpowered to measure outcomes such as fetal or neonatal death or birth injuries.

No data were presented on a number of important variables and outcome measures, such as the rate of or indications for cesarean delivery, the mode and frequency of intrapartum fetal monitoring, birth weight, intrapartum complications (uterine rupture, postpartum hemorrhage), blood transfusions, and infectious morbidity. The study also lacks long-term follow-up data on the infants.

That said, the study was well designed and very well written, and many of the limitations listed above are inherent in all retrospective cohort studies.

Putting these findings in context
These data are not novel, but they are remarkably consistent with other publications that have explored pregnancy outcomes in planned home birth versus hospital delivery from the Netherlands, the United Kingdom, Australia, and the United States, all of which show a higher rate of neonatal complications with planned home birth [see Reference 4 for review].⁴

Moreover, it is likely that the data in the current report significantly underestimate the risks of planned home birth for two reasons:

• Attempted home births that ended in transfer and, ultimately, delivery in a hospital setting (presumably for some unforeseen event such as excessive hemorrhage or uterine rupture or cord prolapse or nonreassuring fetal testing) were classified as hospital births.
• Apgar scores at 5 minutes are assigned by the attending care provider, and there is no way to independently verify their accuracy. Because of their limited training and/or concern about efforts to limit the scope of their practice, “other midwives” may be inclined to assign more favorable Apgar scores.

Who is choosing to deliver at home?
The proportion of US women who delivered outside the hospital setting increased by 29% between 2004 and 2009,⁵ although home births still constitute a minority of low-risk births (0.58% in the current study).

Related Article: Why are well-educated women more likely to choose home birth? Errol R. Norwitz, MD, PhD (Audiocast, November 2013)

One of the more interesting questions raised by this publication is the issue of who is choosing to deliver at home. In this cohort, women who planned home birth were more likely to be older, married, multiparous, white, and well educated. These aren’t exactly the women you would expect to gamble with the lives of their unborn offspring. So why are they choosing to deliver at home?

It could be that they are not well informed about the risks. Alternatively, they may have concluded that, although the relative risk of an adverse event is significantly higher with home birth, the absolute risk is low and acceptable to them. Or it could be that they are frustrated by the lack of autonomy afforded to them in the decisions surrounding antenatal care and the birthing process.

In recent years, more women are asking for minimally invasive births that are physically, emotionally, and socially supported. As hospital-based obstetric care providers, we do not always respect or meet these expectations. We can and should do better.

Women should not have to choose between a good birth experience and medical safety, between social support and hospital resources, between a sense of autonomy and access to life-saving interventions. Although every effort should be taken to make the birthing experience a positive one for the mother and her family as a whole, it should not be done at the expense of safety. I have yet to hear an asphyxiated and brain-damaged child thank his mother’s obstetric care provider for allowing a wonderful birth experience.

What this evidence means for practice
Even in countries where home births are integrated fully into the medical care system and attended by trained and certified nurse-midwives, they are associated with increased risks, including a twofold to threefold increase in the odds of neonatal death.4 In the US, where no such integration exists, home births are dangerous.

Maternity care has come a long way since the 17th Century, when a woman had a 1 in 6 chance of dying in childbirth and only one of every five children lived to enjoy a first birthday. It is appropriate in this era of Obamacare and cost containment that we explore alternative methods. The option of a safe home delivery may well be part of the solution, as it is for many European countries--but until we can be assured that such an approach is safe for both mothers and infants, let's keep home delivery where it belongs...for pizza!

--Errol R. Norwitz, MD, PHD

We want to hear from you! Tell us what you think.

Every morning before I leave for work, I kiss my three children goodbye and tell them, “I love you. Make good choices today.”

This has become my mantra—so much so that, on her way out the door to join her friends at the movies recently, my daughter turned to me and said, “I know, Dad. I know. I’ll make good decisions tonight.”

And what decision is more important than where to deliver your child and who to have in attendance at the birth?

It is said that the passage from the uterus to the outside world that each one of us was forced to negotiate at birth is the most treacherous journey we will ever undertake. Any unnecessary delay or complication can have profound, lifelong consequences.

There is no question that the past few centuries have seen a significant “medicalization” of childbirth, including the relocation of deliveries from the community to a hospital setting, the introduction of male obstetricians, the unfortunate marginalization of midwives and support personnel (doulas), the development of uterotonic drugs, and the evolution of operative vaginal (forceps, vacuum) and cesarean deliveries.

Many of the practices initially introduced by obstetric care providers (including multiple vaginal examinations in labor, induction of labor for a large baby, and active management of labor protocols) have since been shown to be unhelpful in improving pregnancy outcomes, and some practices (such as episiotomy) have even been shown to be harmful.

Related article: Difficult fetal extraction at cesarean delivery: What should you do? Robert L. Barbieri, MD (Editorial, January 2012)

In the midst of this confusion, the one voice that has been lost is that of the patient herself.

Whose birth is it anyway?
The American College of Obstetricians and Gynecologists (ACOG), the American Academy of Pediatrics (AAP), and the American College of Nurse-Midwives (ACNM) all agree that patient autonomy is paramount, and that the final decision of where to deliver and who to have in attendance should be made by the patient herself, ideally in conjunction with her family and her obstetric care provider.^1–3 But an informed decision is only as good as the available data. Regrettably, the literature on how planned home birth compares with hospital delivery in terms of pregnancy outcomes in the United States are sparse.

Related article: Lay midwives the the ObGyn: Is collaboration risky? Lucia DiVenere, MA (May 2012)

How safe is home birth in the United States?
Cheng and colleagues attempt to answer this question by reviewing newborn and maternal outcomes among planned home births versus hospital deliveries in a contemporary low-risk birth cohort. Their retrospective study included low-risk women at term with a singleton vertex live birth in 2008 in 27 of the 50 states using information from the Vital Statistics Natality Data provided by the Centers for Disease Control and Prevention.

Of these 2,081,753 women, 0.58% (n = 12,039) had planned home births, and the remainder delivered in a hospital setting. Women who had an “accidental” (unintended) home birth or who delivered in a freestanding birthing center were excluded. The primary outcome was the risk of a 5-minute Apgar score less than 4. Secondary outcomes included the risk of a 5-minute Apgar score less than 7, assisted ventilation for more than 6 hours, neonatal seizures, admission to the NICU, and a series of maternal outcome measures.

Besides the outcomes listed previously (top of page 24), women with a planned home birth had fewer obstetric interventions, including operative vaginal delivery and labor induction or augmentation. They also were less likely to be given antibiotics during labor (although the authors did not distinguish between antibiotics administered for prophylaxis against group B strep or surgical-site infection versus antibiotics to treat infections such as urinary tract infections or chorioamnionitis).

Of special interest is the fact that neither a prior vaginal delivery (multiparity) nor the absence of a prior cesarean delivery was protective against these adverse events.

The women at highest risk of an adverse event were those who delivered at home under the supervision of “other midwives.” Although these providers were not well defined, this term typically refers to community-based lay midwives whose only “training” consists of an unofficial apprenticeship of variable length. Despite the absence of formal training, the lack of certification and standardization of care, and the existence of legislation in many states banning their activity, such lay midwives continue to encourage and support home birth for both low- and high-risk women in the United States.

Related article: Update on Obstetrics John T. Repke, MD, and Jaimey M. Pauli, MD (January 2012)

Limitations of the study design
Although this dataset contains more than 2 million births, it includes only low-risk women at term and, therefore, is underpowered to measure outcomes such as fetal or neonatal death or birth injuries.

No data were presented on a number of important variables and outcome measures, such as the rate of or indications for cesarean delivery, the mode and frequency of intrapartum fetal monitoring, birth weight, intrapartum complications (uterine rupture, postpartum hemorrhage), blood transfusions, and infectious morbidity. The study also lacks long-term follow-up data on the infants.

That said, the study was well designed and very well written, and many of the limitations listed above are inherent in all retrospective cohort studies.

Putting these findings in context
These data are not novel, but they are remarkably consistent with other publications that have explored pregnancy outcomes in planned home birth versus hospital delivery from the Netherlands, the United Kingdom, Australia, and the United States, all of which show a higher rate of neonatal complications with planned home birth [see Reference 4 for review].⁴

Moreover, it is likely that the data in the current report significantly underestimate the risks of planned home birth for two reasons:

• Attempted home births that ended in transfer and, ultimately, delivery in a hospital setting (presumably for some unforeseen event such as excessive hemorrhage or uterine rupture or cord prolapse or nonreassuring fetal testing) were classified as hospital births.
• Apgar scores at 5 minutes are assigned by the attending care provider, and there is no way to independently verify their accuracy. Because of their limited training and/or concern about efforts to limit the scope of their practice, “other midwives” may be inclined to assign more favorable Apgar scores.

Who is choosing to deliver at home?
The proportion of US women who delivered outside the hospital setting increased by 29% between 2004 and 2009,⁵ although home births still constitute a minority of low-risk births (0.58% in the current study).

Related Article: Why are well-educated women more likely to choose home birth? Errol R. Norwitz, MD, PhD (Audiocast, November 2013)

One of the more interesting questions raised by this publication is the issue of who is choosing to deliver at home. In this cohort, women who planned home birth were more likely to be older, married, multiparous, white, and well educated. These aren’t exactly the women you would expect to gamble with the lives of their unborn offspring. So why are they choosing to deliver at home?

It could be that they are not well informed about the risks. Alternatively, they may have concluded that, although the relative risk of an adverse event is significantly higher with home birth, the absolute risk is low and acceptable to them. Or it could be that they are frustrated by the lack of autonomy afforded to them in the decisions surrounding antenatal care and the birthing process.

In recent years, more women are asking for minimally invasive births that are physically, emotionally, and socially supported. As hospital-based obstetric care providers, we do not always respect or meet these expectations. We can and should do better.

Women should not have to choose between a good birth experience and medical safety, between social support and hospital resources, between a sense of autonomy and access to life-saving interventions. Although every effort should be taken to make the birthing experience a positive one for the mother and her family as a whole, it should not be done at the expense of safety. I have yet to hear an asphyxiated and brain-damaged child thank his mother’s obstetric care provider for allowing a wonderful birth experience.

What this evidence means for practice
Even in countries where home births are integrated fully into the medical care system and attended by trained and certified nurse-midwives, they are associated with increased risks, including a twofold to threefold increase in the odds of neonatal death.4 In the US, where no such integration exists, home births are dangerous.

Maternity care has come a long way since the 17th Century, when a woman had a 1 in 6 chance of dying in childbirth and only one of every five children lived to enjoy a first birthday. It is appropriate in this era of Obamacare and cost containment that we explore alternative methods. The option of a safe home delivery may well be part of the solution, as it is for many European countries--but until we can be assured that such an approach is safe for both mothers and infants, let's keep home delivery where it belongs...for pizza!

--Errol R. Norwitz, MD, PHD

We want to hear from you! Tell us what you think.

This educational supplement to Pediatric News was sponsored by Johnson & Johnson Consumer Products Company.

Topic Highlights

• Introduction—Knowledge About Development and Maintenance of Normal Sleep and Healthy Skin in Infants and Children Continues to Evolve
• Sleep and Development in Infants and Toddlers
• Sleep in Young Children: A Cross-Cultural Perspective
• Sleep Education in Pediatric Residency Programs
• The Impact of Young Children’s Sleep on Maternal Sleep
• An iPhone^® Application for Infant and Toddler Sleep: Concerns of Users
• Intra- and Interpersonal Changes in the Skin Microbiome from Infancy to Adulthood
• Chymotrypsin-Like Protease Activity in the Stratum Corneum is Increased in Atopic Dermatitis and Upon Washing with Soap
• Avena sativa Extracts in Atopic Eczema: A Two-Month Observational Study in Greece

Faculty/Faculty Disclosures

Paul Horowitz, MD, FAAP
Discovery Pediatrics
Valencia, California

Sherrill J. Rudy, MSN, CRNP
School of Nursing and Health Sciences
Robert Morris University
Pittsburgh, Pennsylvania

Dr. Horowitz discloses that he is a paid consultant and Advisory Board member to Johnson & Johnson Consumer Companies, Inc.

Ms. Rudy discloses that she is a paid consultant to Johnson & Johnson Consumer Companies, Inc.

This educational supplement to Pediatric News was sponsored by Johnson & Johnson Consumer Products Company.

Topic Highlights

• Introduction—Knowledge About Development and Maintenance of Normal Sleep and Healthy Skin in Infants and Children Continues to Evolve
• Sleep and Development in Infants and Toddlers
• Sleep in Young Children: A Cross-Cultural Perspective
• Sleep Education in Pediatric Residency Programs
• The Impact of Young Children’s Sleep on Maternal Sleep
• An iPhone^® Application for Infant and Toddler Sleep: Concerns of Users
• Intra- and Interpersonal Changes in the Skin Microbiome from Infancy to Adulthood
• Chymotrypsin-Like Protease Activity in the Stratum Corneum is Increased in Atopic Dermatitis and Upon Washing with Soap
• Avena sativa Extracts in Atopic Eczema: A Two-Month Observational Study in Greece

Faculty/Faculty Disclosures

Paul Horowitz, MD, FAAP
Discovery Pediatrics
Valencia, California

Sherrill J. Rudy, MSN, CRNP
School of Nursing and Health Sciences
Robert Morris University
Pittsburgh, Pennsylvania

Dr. Horowitz discloses that he is a paid consultant and Advisory Board member to Johnson & Johnson Consumer Companies, Inc.

Ms. Rudy discloses that she is a paid consultant to Johnson & Johnson Consumer Companies, Inc.

This educational supplement to Pediatric News was sponsored by Johnson & Johnson Consumer Products Company.

Topic Highlights

• Introduction—Knowledge About Development and Maintenance of Normal Sleep and Healthy Skin in Infants and Children Continues to Evolve
• Sleep and Development in Infants and Toddlers
• Sleep in Young Children: A Cross-Cultural Perspective
• Sleep Education in Pediatric Residency Programs
• The Impact of Young Children’s Sleep on Maternal Sleep
• An iPhone^® Application for Infant and Toddler Sleep: Concerns of Users
• Intra- and Interpersonal Changes in the Skin Microbiome from Infancy to Adulthood
• Chymotrypsin-Like Protease Activity in the Stratum Corneum is Increased in Atopic Dermatitis and Upon Washing with Soap
• Avena sativa Extracts in Atopic Eczema: A Two-Month Observational Study in Greece

Faculty/Faculty Disclosures

Paul Horowitz, MD, FAAP
Discovery Pediatrics
Valencia, California

Sherrill J. Rudy, MSN, CRNP
School of Nursing and Health Sciences
Robert Morris University
Pittsburgh, Pennsylvania

Dr. Horowitz discloses that he is a paid consultant and Advisory Board member to Johnson & Johnson Consumer Companies, Inc.

Ms. Rudy discloses that she is a paid consultant to Johnson & Johnson Consumer Companies, Inc.

Despite the advent of modern chemo- and radioimmunotherapies, the disease course in most mature B-cell malignancies (with the exception of diffuse large B-cell lymphoma [DLBCL] and Burkitt lymphoma) is highlighted by frequent relapses, progressively shorter remissions, and eventual emergence of therapy resistance. An effective salvage therapy in this setting remains an area of unmet medical need. Bruton’s tyrosine kinase (BTK) is a critical component of B-cell–receptor signaling that mediates interactions with the tumor microenvironment and promotes survival and proliferation of malignant B-cells.1,2 The BTK protein itself is a Tec family tyrosine kinase that is activated by spleen tyrosine kinase following B-cell-receptor stimulation and which is then required for downstream events including calcium release, activation of the NFB and NFAT pathways, cell survival and proliferation.1 The fundamental role of BTK in B-cell function is underscored by the human disease X-linked agammaglobulinemia, which is caused by loss of function mutations in BTK.3 These mutations result in the virtual absence of all B cells and immunoglobulins, leading to recurrent bacterial infections. Ibrutinib (formally known as PCI-32765) is the first-in-class BTK inhibitor to enter clinical trials. In a multicenter phase 1 dose-escalating study, 56 patients with relapsed or refractory B-cell lymphomas received escalated doses of oral ibrutinib either on an intermittent or continuous daily dosing schedule.4 The most common adverse effects were grade 1-2 nonhematologic toxicities, which included rash, nausea, fatigue, diarrhea, muscle spasms/myalgia, and arthralgia. An overall response rate (ORR) of 60% was achieved across all histological types with the best efficacy seen in patients with mantle cell lymphoma (MCL; 78%) and chronic lymphocytic leukemia (CLL; 68%).

Click on the PDF icon at the top of this article to read the full article.

Despite the advent of modern chemo- and radioimmunotherapies, the disease course in most mature B-cell malignancies (with the exception of diffuse large B-cell lymphoma [DLBCL] and Burkitt lymphoma) is highlighted by frequent relapses, progressively shorter remissions, and eventual emergence of therapy resistance. An effective salvage therapy in this setting remains an area of unmet medical need. Bruton’s tyrosine kinase (BTK) is a critical component of B-cell–receptor signaling that mediates interactions with the tumor microenvironment and promotes survival and proliferation of malignant B-cells.1,2 The BTK protein itself is a Tec family tyrosine kinase that is activated by spleen tyrosine kinase following B-cell-receptor stimulation and which is then required for downstream events including calcium release, activation of the NFB and NFAT pathways, cell survival and proliferation.1 The fundamental role of BTK in B-cell function is underscored by the human disease X-linked agammaglobulinemia, which is caused by loss of function mutations in BTK.3 These mutations result in the virtual absence of all B cells and immunoglobulins, leading to recurrent bacterial infections. Ibrutinib (formally known as PCI-32765) is the first-in-class BTK inhibitor to enter clinical trials. In a multicenter phase 1 dose-escalating study, 56 patients with relapsed or refractory B-cell lymphomas received escalated doses of oral ibrutinib either on an intermittent or continuous daily dosing schedule.4 The most common adverse effects were grade 1-2 nonhematologic toxicities, which included rash, nausea, fatigue, diarrhea, muscle spasms/myalgia, and arthralgia. An overall response rate (ORR) of 60% was achieved across all histological types with the best efficacy seen in patients with mantle cell lymphoma (MCL; 78%) and chronic lymphocytic leukemia (CLL; 68%).

Click on the PDF icon at the top of this article to read the full article.

Despite the advent of modern chemo- and radioimmunotherapies, the disease course in most mature B-cell malignancies (with the exception of diffuse large B-cell lymphoma [DLBCL] and Burkitt lymphoma) is highlighted by frequent relapses, progressively shorter remissions, and eventual emergence of therapy resistance. An effective salvage therapy in this setting remains an area of unmet medical need. Bruton’s tyrosine kinase (BTK) is a critical component of B-cell–receptor signaling that mediates interactions with the tumor microenvironment and promotes survival and proliferation of malignant B-cells.1,2 The BTK protein itself is a Tec family tyrosine kinase that is activated by spleen tyrosine kinase following B-cell-receptor stimulation and which is then required for downstream events including calcium release, activation of the NFB and NFAT pathways, cell survival and proliferation.1 The fundamental role of BTK in B-cell function is underscored by the human disease X-linked agammaglobulinemia, which is caused by loss of function mutations in BTK.3 These mutations result in the virtual absence of all B cells and immunoglobulins, leading to recurrent bacterial infections. Ibrutinib (formally known as PCI-32765) is the first-in-class BTK inhibitor to enter clinical trials. In a multicenter phase 1 dose-escalating study, 56 patients with relapsed or refractory B-cell lymphomas received escalated doses of oral ibrutinib either on an intermittent or continuous daily dosing schedule.4 The most common adverse effects were grade 1-2 nonhematologic toxicities, which included rash, nausea, fatigue, diarrhea, muscle spasms/myalgia, and arthralgia. An overall response rate (ORR) of 60% was achieved across all histological types with the best efficacy seen in patients with mantle cell lymphoma (MCL; 78%) and chronic lymphocytic leukemia (CLL; 68%).

Click on the PDF icon at the top of this article to read the full article.

Pazopanib was well tolerated and appeared to be of clinical benefit in children with soft tissue sarcoma in a phase I study. Although the findings are preliminary, eight children in the trial achieved stable disease and two achieved a partial response.

"The clinical activity of pazopanib is encouraging in this heavily pretreated pediatric population," said Dr. Julia Glad Bender, of Columbia University Medical Center, New York, and her associates (J. Clin. Oncol. 2013;31:3034-43).

Pazopanib (Votrient) is approved by the Food and Drug Administration as a treatment for adult patients with soft tissue sarcoma and in those with advanced renal cell carcinoma. The drug inhibited cell proliferation, angiogenesis, and possibly tumor growth in pediatric xenografts, prompting the research team to evaluate pazopanib’s therapeutic potential in children.

The multicenter phase I study examined the pharmacokinetic and pharmacodynamic properties of two formulations of pazopanib in children with soft tissue sarcoma or other refractory solid tumors. Overall, 51 children with a median age of 12.9 years and recurrent or refractory solid or primary central nervous system tumors were evaluated in the trial.

For the first component of the trial, the maximum tolerated dose (MTD) of a tablet formulation of pazopanib was determined in 25 children who had a median age of 13.5 years. The starting dose of pazopanib was 275 mg/m² given every day in 28-day cycles for up to a maximum of 24 cycles. The MTD was found to be 450 mg/m².

The researchers next determined the MTD of a powder suspension formulation of the drug based on the tablet MTD in 16 children with a median age of 10.5 years. The suspension MTD was found to be 160 mg/m².

Finally, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used at the start of and after 15 days’ treatment in 10 children with a median age of 17.2 years. All received pazopanib tablets at the MTD of 450 mg/m². The aim was to see if there was any sign of a change in tumor angiogenesis in response to treatment.

The most common adverse effects seen with pazopanib treatment were gastrointestinal (diarrhea, nausea, and vomiting), fatigue, proteinuria, and hypertension. Grade 3-4 toxicities that limited dosing in the first cycle of treatment included elevations in lipase, amylase and alanine transaminase, proteinuria, and hypertension. There was a single (grade 4) case of intracranial hemorrhage in a child with occult brain metastases.

"Overall toxicity seemed to correlate with exposure rather than dose," the researchers wrote. The bioavailability of pazopanib appeared to be higher with the suspension than with the tablet formulation, so there might be a relationship between higher steady state plasma trough concentrations and the development of hypertension.

"In adults, elevated blood pressure has been suggested as a correlative marker for improved antitumor efficacy of VEGF [vascular endothelial growth factor] pathway inhibitors," the researchers wrote. "Additional studies are warranted to determine whether hypertension can be used to optimize dose or predict clinical benefit in children."

Eight patients in the trial had stable disease for 6 months or more, and seven of those children had soft tissue sarcomas. Partial responses were seen in two children – one with a desmoplastic small round cell tumor and one with a hepatoblastoma. The latter patient had to be removed from the study due to recurrent neutropenia after 12 cycles.

Results of the DCE-MRI analysis showed a decrease in tumor blood volume from a mean of 16% at the start of treatment to 7% at the end of pazopanib treatment (P = .004).

"To our knowledge, this is the first pediatric, multicenter trial to systematically evaluate DCE-MRI in soft tissue sarcoma, demonstrating the feasibility of performing such studies in a clinical trial network," Dr. Bender and team commented.

"Within the imaging stratum, all patients with interpretable studies had a decrease in tumor blood volume and permeability consistent with the antiangiogenic mechanism of pazopanib." Due to the small number of children evaluated, however, it is not possible to correlate the decrease in tumor blood volume with any clinical benefit.

A phase II trial is planned to further determine the pharmacokinetics and pharmacodynamic of pazopanib in children with soft tissue sarcomas and other refractory solid tumors.

The study was supported by grants from the Alex’s Lemonade Stand Foundation, Columbia University, GlaxoSmithKline, and the National Institutes of Health. Dr. Bender has acted as an unpaid advisor to GlaxoSmithKline. The other authors reported no conflicts of interest.

[email protected]

Pazopanib was well tolerated and appeared to be of clinical benefit in children with soft tissue sarcoma in a phase I study. Although the findings are preliminary, eight children in the trial achieved stable disease and two achieved a partial response.

"The clinical activity of pazopanib is encouraging in this heavily pretreated pediatric population," said Dr. Julia Glad Bender, of Columbia University Medical Center, New York, and her associates (J. Clin. Oncol. 2013;31:3034-43).

Pazopanib (Votrient) is approved by the Food and Drug Administration as a treatment for adult patients with soft tissue sarcoma and in those with advanced renal cell carcinoma. The drug inhibited cell proliferation, angiogenesis, and possibly tumor growth in pediatric xenografts, prompting the research team to evaluate pazopanib’s therapeutic potential in children.

The multicenter phase I study examined the pharmacokinetic and pharmacodynamic properties of two formulations of pazopanib in children with soft tissue sarcoma or other refractory solid tumors. Overall, 51 children with a median age of 12.9 years and recurrent or refractory solid or primary central nervous system tumors were evaluated in the trial.

For the first component of the trial, the maximum tolerated dose (MTD) of a tablet formulation of pazopanib was determined in 25 children who had a median age of 13.5 years. The starting dose of pazopanib was 275 mg/m² given every day in 28-day cycles for up to a maximum of 24 cycles. The MTD was found to be 450 mg/m².

The researchers next determined the MTD of a powder suspension formulation of the drug based on the tablet MTD in 16 children with a median age of 10.5 years. The suspension MTD was found to be 160 mg/m².

Finally, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used at the start of and after 15 days’ treatment in 10 children with a median age of 17.2 years. All received pazopanib tablets at the MTD of 450 mg/m². The aim was to see if there was any sign of a change in tumor angiogenesis in response to treatment.

The most common adverse effects seen with pazopanib treatment were gastrointestinal (diarrhea, nausea, and vomiting), fatigue, proteinuria, and hypertension. Grade 3-4 toxicities that limited dosing in the first cycle of treatment included elevations in lipase, amylase and alanine transaminase, proteinuria, and hypertension. There was a single (grade 4) case of intracranial hemorrhage in a child with occult brain metastases.

"Overall toxicity seemed to correlate with exposure rather than dose," the researchers wrote. The bioavailability of pazopanib appeared to be higher with the suspension than with the tablet formulation, so there might be a relationship between higher steady state plasma trough concentrations and the development of hypertension.

"In adults, elevated blood pressure has been suggested as a correlative marker for improved antitumor efficacy of VEGF [vascular endothelial growth factor] pathway inhibitors," the researchers wrote. "Additional studies are warranted to determine whether hypertension can be used to optimize dose or predict clinical benefit in children."

Eight patients in the trial had stable disease for 6 months or more, and seven of those children had soft tissue sarcomas. Partial responses were seen in two children – one with a desmoplastic small round cell tumor and one with a hepatoblastoma. The latter patient had to be removed from the study due to recurrent neutropenia after 12 cycles.

Results of the DCE-MRI analysis showed a decrease in tumor blood volume from a mean of 16% at the start of treatment to 7% at the end of pazopanib treatment (P = .004).

"To our knowledge, this is the first pediatric, multicenter trial to systematically evaluate DCE-MRI in soft tissue sarcoma, demonstrating the feasibility of performing such studies in a clinical trial network," Dr. Bender and team commented.

"Within the imaging stratum, all patients with interpretable studies had a decrease in tumor blood volume and permeability consistent with the antiangiogenic mechanism of pazopanib." Due to the small number of children evaluated, however, it is not possible to correlate the decrease in tumor blood volume with any clinical benefit.

A phase II trial is planned to further determine the pharmacokinetics and pharmacodynamic of pazopanib in children with soft tissue sarcomas and other refractory solid tumors.

The study was supported by grants from the Alex’s Lemonade Stand Foundation, Columbia University, GlaxoSmithKline, and the National Institutes of Health. Dr. Bender has acted as an unpaid advisor to GlaxoSmithKline. The other authors reported no conflicts of interest.

[email protected]

Pazopanib was well tolerated and appeared to be of clinical benefit in children with soft tissue sarcoma in a phase I study. Although the findings are preliminary, eight children in the trial achieved stable disease and two achieved a partial response.

"The clinical activity of pazopanib is encouraging in this heavily pretreated pediatric population," said Dr. Julia Glad Bender, of Columbia University Medical Center, New York, and her associates (J. Clin. Oncol. 2013;31:3034-43).

Pazopanib (Votrient) is approved by the Food and Drug Administration as a treatment for adult patients with soft tissue sarcoma and in those with advanced renal cell carcinoma. The drug inhibited cell proliferation, angiogenesis, and possibly tumor growth in pediatric xenografts, prompting the research team to evaluate pazopanib’s therapeutic potential in children.

The multicenter phase I study examined the pharmacokinetic and pharmacodynamic properties of two formulations of pazopanib in children with soft tissue sarcoma or other refractory solid tumors. Overall, 51 children with a median age of 12.9 years and recurrent or refractory solid or primary central nervous system tumors were evaluated in the trial.

For the first component of the trial, the maximum tolerated dose (MTD) of a tablet formulation of pazopanib was determined in 25 children who had a median age of 13.5 years. The starting dose of pazopanib was 275 mg/m² given every day in 28-day cycles for up to a maximum of 24 cycles. The MTD was found to be 450 mg/m².

The researchers next determined the MTD of a powder suspension formulation of the drug based on the tablet MTD in 16 children with a median age of 10.5 years. The suspension MTD was found to be 160 mg/m².

Finally, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used at the start of and after 15 days’ treatment in 10 children with a median age of 17.2 years. All received pazopanib tablets at the MTD of 450 mg/m². The aim was to see if there was any sign of a change in tumor angiogenesis in response to treatment.

The most common adverse effects seen with pazopanib treatment were gastrointestinal (diarrhea, nausea, and vomiting), fatigue, proteinuria, and hypertension. Grade 3-4 toxicities that limited dosing in the first cycle of treatment included elevations in lipase, amylase and alanine transaminase, proteinuria, and hypertension. There was a single (grade 4) case of intracranial hemorrhage in a child with occult brain metastases.

"Overall toxicity seemed to correlate with exposure rather than dose," the researchers wrote. The bioavailability of pazopanib appeared to be higher with the suspension than with the tablet formulation, so there might be a relationship between higher steady state plasma trough concentrations and the development of hypertension.

"In adults, elevated blood pressure has been suggested as a correlative marker for improved antitumor efficacy of VEGF [vascular endothelial growth factor] pathway inhibitors," the researchers wrote. "Additional studies are warranted to determine whether hypertension can be used to optimize dose or predict clinical benefit in children."

Eight patients in the trial had stable disease for 6 months or more, and seven of those children had soft tissue sarcomas. Partial responses were seen in two children – one with a desmoplastic small round cell tumor and one with a hepatoblastoma. The latter patient had to be removed from the study due to recurrent neutropenia after 12 cycles.

Results of the DCE-MRI analysis showed a decrease in tumor blood volume from a mean of 16% at the start of treatment to 7% at the end of pazopanib treatment (P = .004).

"To our knowledge, this is the first pediatric, multicenter trial to systematically evaluate DCE-MRI in soft tissue sarcoma, demonstrating the feasibility of performing such studies in a clinical trial network," Dr. Bender and team commented.

"Within the imaging stratum, all patients with interpretable studies had a decrease in tumor blood volume and permeability consistent with the antiangiogenic mechanism of pazopanib." Due to the small number of children evaluated, however, it is not possible to correlate the decrease in tumor blood volume with any clinical benefit.

A phase II trial is planned to further determine the pharmacokinetics and pharmacodynamic of pazopanib in children with soft tissue sarcomas and other refractory solid tumors.

The study was supported by grants from the Alex’s Lemonade Stand Foundation, Columbia University, GlaxoSmithKline, and the National Institutes of Health. Dr. Bender has acted as an unpaid advisor to GlaxoSmithKline. The other authors reported no conflicts of interest.

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