The authors report no financial relationships relevant to this article.

CASE 1: Cystic mass in patient’s only remaining ovary

Mrs. R is a 29-year-old G1P1 who underwent a right oophorectomy, with a midline incision, for a dermoid cyst at the time of cesarean delivery. She now has a left ovarian cyst. Preoperative ultrasonography (US) reveals that it measures 3.5×4.2×3.7 cm and has both solid components and a multiloculated appearance, consistent with a dermoid cyst.

How common is this scenario?

Studies predict that one of every three women will undergo surgical management of an adnexal mass at some point in her life.¹ This troubling statistic prompts several critical questions:

• How do we handle the workup for these women so that only appropriate patients undergo surgery?
• How often will a mass be malignant?
• How can we safely remove an adnexal mass to maximize patient safety, reduce overall recovery time, and prevent less favorable outcomes in women who are eventually found to have a malignancy?

A thorough workup and, sometimes, conservative management can prevent unnecessary surgery that may lead to early menopause or surgical complications. And maximizing the use of minimally invasive techniques in women who do require surgery can shorten hospital stay and recovery time. At the time of surgery, careful abdominal entry and meticulous surgical dissection and mass removal can limit the potential risks of laparoscopic excision in women who have an ultimate diagnosis of cancer.

In this article, we review the workup for women who have an adnexal mass, describe patient-selection criteria for laparoscopic surgery, including the risks and benefits of this approach ( TABLE 1 ), and present several techniques to safely manage a mass with potentially malignant histology via laparoscopy.

TABLE 1

There are benefits and risks to managing an adnexal mass laparoscopically

Begin with the physical

When a woman is known to have a pelvic mass, the aim of the office exam is to 1) identify characteristics that suggest malignancy and 2) rule out nongynecologic causes of the mass. Physical findings that are worrisome for a malignant process include:

• fixed or nodular pelvic mass
• bilateral masses
• nodular abdominal mass
• ascites
• pleural effusion on auscultation or percussion of the lung.

Although these findings can be present under benign conditions, they increase the risk that a malignancy will be detected at surgery.

Other causes of a pelvic mass should also be considered, including infection (pelvic abscess) and tumors of the colon, particularly when the pelvic mass occurs on the left side.

Some symptoms, though vague, are worth noting

Although ovarian cancer was once thought to be a silent disease, recent research has shown that bloating, pelvic or abdominal pain, early satiety, and urinary frequency and urgency are more common among women with ovarian cancer than among healthy controls and patients in high-risk screening clinics.^2-4 Although these symptoms are generally nonspecific, they merit attention if they occur more than 12 times a month and have been present for less than 1 year. When they meet these criteria, the symptoms have a sensitivity for diagnosing early- and late-stage ovarian cancer of 56.7% and 79.5%, respectively.⁴

Sensitivity for the diagnosis of early-stage ovarian cancer may be as high as 80% when the symptom index score is combined with an elevated level of the tumor marker CA 125.³

Transvaginal US is crucial

Transvaginal US is now standard practice to obtain high-resolution images of an adnexal mass. Grayscale US has traditionally been used alone for evaluation.

Specificity is typically lower in women who are premenopausal because many benign lesions, such as endometrioma, have a similar sonographic appearance to cancer.

A number of US scoring algorithms have now been proposed to aid in the triage of women who have an adnexal mass. Sensitivity of these algorithms ranges from 65% to 100%; specificity, from 77% to 95%.⁵

CA 125 is the standard tumor marker

For the past two decades, CA 125 has been the standard serum marker in the screening of high-risk women for ovarian cancer and the triage of women who have an adnexal mass.

This blood test has been studied widely since its introduction in 1983. It typically has sensitivity of 75% to 85% and specificity of 85% to 95% in identifying women who have ovarian cancer. However, it is elevated in only 50% to 60% of women who have stage I ovarian cancer. Its lack of specificity and poor positive predictive value have kept researchers busy trying to identify other serum markers, for both ovarian cancer and identification of high-risk pelvic masses.

Our recommended workup and management of adnexal masses In postmenopausal women who had a pelvic mass, one study found that a CA 125 level above 65 IU/mL had sensitivity of 71% and specificity of 92.5% in the identification of ovarian cancer.⁶ Another group found that CA 125 levels above 65 IU/mL were more than 95% sensitive in the diagnosis of ovarian cancer in postmenopausal women.⁷

Several studies have combined CA 125 with other markers or with US to screen high-risk women or triage those who have an adnexal mass. These studies have shown modest improvements in sensitivity but usually lower specificity than with CA 125 testing alone.

Markers that may be used for suspected sex cord stromas and germ-cell tumors are:

• lactate dehydrogenase (LDH) for dysgerminomas
• alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) for yolk sac tumors
• testosterone for Sertoli-Leydig cell tumors
• inhibin A and B for granulosa cell tumors.

An algorithm for working up and managing adnexal masses appears above.

How to gain abdominal access

In the opening case, the patient clearly has a benign mass. The treatment? Safe entry into the peritoneal cavity to remove the cyst and as little normal tissue as possible. This is critical in this patient because she has only one ovary.

Peritoneal access for abdominal and pelvic laparoscopy has been studied widely. Options include:

• direct insertion using a Veress needle
• open laparoscopy
• direct trocar insertion.

The technique usually depends on the preference of the surgeon. The primary goal of abdominal entry is to minimize the risk of injury, particularly unrecognized injury.

Data on complication rates show no definite benefit for open versus closed techniques in the prevention of injury to underlying viscera. However, evidence does suggest that the open technique may lower the risk of major vascular injury.⁸

We employ direct trocar insertion using radially expanding or optical trocars.

The Veress needle option

When the Veress needle is used to gain intraperitoneal access, data indicate that initial intraperitoneal pressure below 10 mm Hg is a reliable marker for peritoneal entry, even in obese patients.⁹ Insufflation pressure as high as 25 to 30 mm Hg prior to placement of the initial trocar is safe from a cardiopulmonary standpoint and may allow easier entry with a nonbladed trocar.¹⁰

Tests to confirm intraperitoneal placement of the Veress needle, such as the hanging-drop test or saline flush, do not appear to offer any additional useful information.¹¹

Open laparoscopy is suitable when adhesions are unlikely

Open laparoscopy is typically performed by making a minilaparotomy incision at the umbilicus and then dissecting and entering the peritoneal cavity. A blunt-tip trocar is inserted.

The disadvantage of this approach is that there may be extensive adhesions under the umbilicus, and it is difficult to dissect such adhesions sufficiently to introduce a cannula and laparoscope. Adhesions left behind often obscure the field of view after introduction of the trocar.

Our preference? Left upper-quadrant insertion

In Case 1, the previous midline incision mandates an alternative approach. When abdominal entry at the umbilicus is unsuccessful or potentially difficult because of an earlier midline incision, umbilical hernia repair, or history of multiple lower abdominal or pelvic surgeries, a left upper-quadrant insertion is useful. It is, in fact, our preferred technique, and involves a small incision at the midclavicular line 5 cm below the left costal margin, at a site called Palmer’s point.

The direction of insertion usually ranges from 45° to 90°, depending on the patient’s body weight. If the trocar is placed properly, the closest organs are the stomach and the left lobe of the liver (4 to 6 cm).¹² Given the stomach’s close proximity, it should be decompressed with an orogastric tube prior to trocar insertion.

Several studies have demonstrated the safety and efficacy of this entry technique.^12-14 It can be helpful in cases that involve difficult access. We usually use a 5-mm primary trocar site for a 5-mm laparoscope. Modern optics allow for a pristine view with these small scopes, eliminating the need to close fascia and perhaps causing less pain at the incision.

Accessory trocar sites facilitate complex technique

We usually use three accessory sites. Two of them are lower-quadrant ports that are placed 2 cm medial and 2 cm cephalad to the anterior superior iliac spine. This area generally lies well away from the inferior epigastric vessels and remains above the area of the ilioinguinal and iliohypogastric nerves, making it a safer point of insertion.¹⁵ One trocar is 5 mm in size and the other is 10 mm. The larger one is used to extract the specimen.

We place an additional 5-mm port lateral to the rectus muscle at the level of the umbilicus. This allows the principal surgeon to use two instruments (a toothed forceps and scissors) comfortably while the assistant holds the laparoscope and assists with a grasper.

Does the type of trocar matter?

No randomized studies have directly compared all types of trocars. Options include:

• a pyramidal tip (as in reusable trocars) or shielded tip
• radial expansion
• visible entry
• blunt (Hasson-type) trocar.

Safety data on direct comparison of trocars are limited, but it appears that a radially expanding trocar may offer less port-site pain and potentially less bleeding than a traditional cutting trocar.¹⁶ Moreover, the rate of hernia at the port site appears to be relatively low with a radially expanding trocar, even when fascia is left unclosed at a 10-mm site.¹⁷

None of these trocars appears to be clearly superior at avoiding visceral or vascular injury.

Technique of laparoscopic cyst removal

A video clip of the surgery is linked to this article in the Video Library at www.obgmanagement.com. In this case, a trocar was inserted in the left upper quadrant, and a laparoscopic cystectomy was initiated using the trocars already specified.

The peritoneal cavity and adnexa were inspected, followed by pelvic washings, as detailed in TABLE 2 . Next, the ovarian cortex was incised ( FIGURE 1A ) with scissors using bipolar or unipolar energy, typically at a low power setting, such as 12 to 15 watts.

It was relatively easy to develop a tissue plane between the cortex and underlying dermoid cyst using simple or aqua-dissection ( FIGURE 1B and C ). The cyst was enucleated without rupture and inserted into a specimen bag through a 10-mm port ( FIGURE 1D ). (The specimen bags generally are available in 10-mm and 15-mm sizes.) Once the trocar was removed, the entire specimen was brought out through the incision ( FIGURE 1E ).

Cystic masses can generally be carefully aspirated using a laparoscopic needle or angiocath, or they can be incised and drained using a standard suction device. Manufacturers of most specimen bags do not recommend the morcellation of tissue within the bag because of the potential for rupture of the bag with tumor spillage or injury to underlying structures.

Occasionally, the mass remains too large to remove after drainage of the cyst fluid. Remedies include enlarging the port site with a scalpel or using a gallbladder speculum to increase the diameter of the port site ( FIGURE 1E ). If possible, the incision should be large enough to deliver the entire bag intact. Use of excessive force will rupture the bag and may cause the specimen to be lost or malignant cells to be inadvertently spilled (in the case of a cancer diagnosis).

TABLE 2

Take these 10 steps to safe laparoscopic surgery

FIGURE 1 Laparoscopic cyst removal

Begin by incising the cortex using scissors with or without an energy source.

Dissect the cyst free from the cortex using sharp dissection.

Remove the cyst from the ovary.

Place the cyst in a specimen bag, and …

… bring it to the surface for extraction. The abdominal incision may have to be enlarged to accommodate the specimen.

CASE 1: OUTCOME

The patient’s cyst is removed intact and she is discharged home. Rupture of a dermoid cyst is not associated with any problems as long as copious irrigation is used to aspirate the cyst content.¹⁸ Other cysts, such as endometriomas, may not be as easily dissected, and rupture is inevitable.

CASE 2: Symptoms suggestive of cancer

Mrs. B is a 47-year-old woman who reports abdominal bloating for the past 3 weeks. She also complains of early satiety and occasional constipation. She has no history of cancer, but her sister was given a diagnosis of breast cancer at 41 years of age, and her maternal aunt had breast cancer at 55 years.

Mrs. B is moderately obese, with a nontender abdomen and no palpable mass. Her pelvic exam also is negative for a mass or nodularity, but the extent of the exam is limited by body habitus. Her physician orders a transvaginal US, which reveals a 6-cm complex mass with thin septation and a 1-cm solid nodule, with no definite blood flow. The patient’s CA 125 level is 80 IU/mL, which we consider to be within the low-risk range for a premenopausal woman.

The patient is counseled about the need to have the mass removed and is scheduled for laparoscopic right salpingooophorectomy. Given the family history of breast cancer, the physician also requests consultation with a gynecologic oncologist, who agrees to assist with surgery and perform a laparotomy and staging in the event that a malignancy is diagnosed.

Is the mass likely to be malignant?

Given the patient’s family history of breast cancer, the recent onset of symptoms associated with ovarian cancer,² and the characteristics of the mass (complex, with a nodule), malignancy is possible. This patient has an intermediate risk of cancer and requires additional counseling and planning.

However, most women who undergo laparoscopy for removal of an adnexal mass have benign pathologic findings.

What is the real risk of ovarian cancer?

The lifetime risk of developing ovarian cancer in the general population remains stable at approximately 1 in 70 women, with a mean age at diagnosis of 63 years.¹⁹ Ninety percent of ovarian cancer cases are sporadic, and less than 10% can be linked to genetic syndromes.

Women who have mutations in the BRCA1 gene carry a lifetime risk of ovarian cancer of up to 50%, and women who have mutations in BRCA2 have a lifetime risk of up to 25%.^20,21 Women who have mutations associated with Lynch II syndrome or Hereditary Nonpolyposis Colorectal Cancer syndrome may have a lifetime risk of ovarian cancer of 12%.^22,23

Some women who have a strong family history of breast and ovarian cancer do not carry a known mutation, but are likely to be at increased risk.

Additional risk factors known to be associated with ovarian cancer are nulliparity and infertility. However, the single most important risk factor for epithelial ovarian cancer is age.

Risk-reducing strategies include:

• screening
• prophylactic bilateral salpingooophorectomy (PBSO)
• use of oral contraceptives.^20,24-26

In the case of PBSO, it is imperative to ensure that all ovarian surface epithelium is removed. This means excising the infundibulopelvic ligament at least 1.5 cm above the proximal end of the ovary and excising any adjacent tissue to which the ovary is adherent (including pelvic sidewall peritoneum). Both requirements are easily achieved using the techniques outlined here.

Who should perform surgery?

The American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Oncologists (SGO) have published guidelines for referral to a gynecologic oncologist ( TABLE 3 ). When Im and colleagues reviewed the records of more than 1,000 women who underwent surgery for a pelvic mass at six institutions over 12 months, they found that 70% of premenopausal women and 94% of postmenopausal women who were diagnosed with ovarian cancer were properly referred to a qualified subspecialist.²⁷ “Over”-referral occurred in 30% to 40% of women who had a benign mass, but may be preferable given the importance of proper staging and debulking to survival.

ACOG and the SGO recommend referral for women who have:

• elevated tumor markers
• ascites
• a fixed or nodular mass
• a strong family history of breast or ovarian cancer.

Consider preoperative referral of all high-risk and, probably, intermediate-risk women, depending on the availability of qualified specialists for complete surgical staging.

In addition, women need to be counseled thoroughly about the possibility that a malignancy will be diagnosed by frozen section, necessitating additional surgical procedures.

TABLE 3

Your patient has a newly diagnosed pelvic mass. Should you refer her?

Technique of laparoscopic adnexectomy

In Case 2, an umbilical site was chosen for the primary cannula. In general, the direction of insertion depends on the patient’s body habitus. Heavier patients have a thicker abdominal wall and an umbilicus below the level of the aortic bifurcation. In these women, the angle of insertion should be adjusted from the usual 45° (for patients of normal weight) to an angle nearer to 90°. Lateral ports are typical, as in Case 1.

Treat every mass like cancer

Laparoscopic excision of an adnexal mass can be safe and effective, with better outcomes and recovery than with laparotomy, provided the surgeon adheres to basic principles ( TABLE 2 ). This means treating every mass as though it is potentially malignant, and thoroughly inspecting the abdominal cavity before and after excision of the mass.

Know the retroperitoneal space

As with Case 1, successful laparoscopic excision of an adnexal mass begins with inspection of the peritoneal cavity, abdominopelvic washings, and identification of both the infundibulopelvic ligament and ureter. Knowledge of the retroperitoneal space can be of great value in difficult cases that involve significant pelvic adhesions or sidewall fibrosis. We generally use a retroperitoneal approach for laparoscopic adnexectomy ( FIGURE 2A ).

In our typical approach, we incise the peritoneum lateral to the uteroovarian ligament and continue the incision up the pelvic sidewall lateral to the infundibulopelvic ligament and up along the paracolic gutter, if needed ( FIGURE 2A ). We then mobilize the medial leaf of the broad ligament from the sidewall using blunt dissection between the external iliac vessels laterally and the ureter medially ( FIGURE 2B ).

Once we have identified the ureter, we use scissors to create a window in the medial leaf of the broad ligament just beneath the gonadal vessels. We then use an energy source to occlude and transect the pedicle. Using this technique, we secure the infundibulopelvic ligaments and safely mobilize the ureter before initiating more aggressive sidewall dissection distally for adhesions or fibrosis.

Once the ureter is mobilized, we excise the involved peritoneum along with the mass. We then seal and transect the uteroovarian ligament.

FIGURE 2 The retroperitoneal approach

Grasp and incise the peritoneum just lateral to the adnexal mass and enter the retroperitoneal space, where loose areolar tissue is visible, with the ureter seen on the medial leaf of the broad ligament.

After dissecting this tissue, identify the ureter and internal iliac vessels.

Remove the mass in a bag

Once the mass is excised, we place it in a laparoscopic bag, as described for Case 1. Solid adnexal masses are problematic because they are not amenable to drainage, and morcellation is usually discouraged. Laparoscopic excision can still be carried out, and a minilaparotomy or posterior colpotomy can be used to extract the mass in a bag. Patients managed in this way still have a complication rate similar to or lower than that of patients undergoing laparotomy for oophorectomy; they also recover faster.

Risks in cases of malignancy

The risk of tumor spillage in laparoscopic surgery can be lowered using laparoscopically guided minilaparotomy techniques. Preoperative rupture appears to be more predictive of outcome.²⁸

The concern about metastatic implants in a laparoscopic port site in patients who have gynecologic cancer is real, with an incidence ranging from 0.97% to 1.1%. The phenomenon usually affects women who had ovarian cancer and is most common after laparoscopy with findings of ascites, carcinomatosis, or persistent disease (in the case of second-look laparoscopy performed after completion of primary therapy for ovarian cancer).

These data suggest that port-site implantation is not a concern that should deter clinicians from laparoscopic evaluation of a suspected ovarian neoplasm unless a patient presents with ascites or carcinomatosis suggestive of advanced disease.²⁹

Data are limited regarding delays in definitive therapy. One study suggests that definitive staging on the day of rupture does not influence overall outcome, but delay by more than 2 weeks may lead to poorer prognosis.³⁰

CASE 2: OUTCOME

Laparoscopy is performed. On initial inspection, the peritoneal cavity is unremarkable. The right ovary is multicystic with normal surface anatomy. The mass is somewhat adherent to the pelvic sidewall. Adnexectomy is performed, and frozen section reveals the mass to be a serous cystadenoma.

The authors report no financial relationships relevant to this article.

CASE 1: Cystic mass in patient’s only remaining ovary

Mrs. R is a 29-year-old G1P1 who underwent a right oophorectomy, with a midline incision, for a dermoid cyst at the time of cesarean delivery. She now has a left ovarian cyst. Preoperative ultrasonography (US) reveals that it measures 3.5×4.2×3.7 cm and has both solid components and a multiloculated appearance, consistent with a dermoid cyst.

How common is this scenario?

Studies predict that one of every three women will undergo surgical management of an adnexal mass at some point in her life.¹ This troubling statistic prompts several critical questions:

• How do we handle the workup for these women so that only appropriate patients undergo surgery?
• How often will a mass be malignant?
• How can we safely remove an adnexal mass to maximize patient safety, reduce overall recovery time, and prevent less favorable outcomes in women who are eventually found to have a malignancy?

A thorough workup and, sometimes, conservative management can prevent unnecessary surgery that may lead to early menopause or surgical complications. And maximizing the use of minimally invasive techniques in women who do require surgery can shorten hospital stay and recovery time. At the time of surgery, careful abdominal entry and meticulous surgical dissection and mass removal can limit the potential risks of laparoscopic excision in women who have an ultimate diagnosis of cancer.

In this article, we review the workup for women who have an adnexal mass, describe patient-selection criteria for laparoscopic surgery, including the risks and benefits of this approach ( TABLE 1 ), and present several techniques to safely manage a mass with potentially malignant histology via laparoscopy.

TABLE 1

There are benefits and risks to managing an adnexal mass laparoscopically

Begin with the physical

When a woman is known to have a pelvic mass, the aim of the office exam is to 1) identify characteristics that suggest malignancy and 2) rule out nongynecologic causes of the mass. Physical findings that are worrisome for a malignant process include:

• fixed or nodular pelvic mass
• bilateral masses
• nodular abdominal mass
• ascites
• pleural effusion on auscultation or percussion of the lung.

Although these findings can be present under benign conditions, they increase the risk that a malignancy will be detected at surgery.

Other causes of a pelvic mass should also be considered, including infection (pelvic abscess) and tumors of the colon, particularly when the pelvic mass occurs on the left side.

Some symptoms, though vague, are worth noting

Although ovarian cancer was once thought to be a silent disease, recent research has shown that bloating, pelvic or abdominal pain, early satiety, and urinary frequency and urgency are more common among women with ovarian cancer than among healthy controls and patients in high-risk screening clinics.^2-4 Although these symptoms are generally nonspecific, they merit attention if they occur more than 12 times a month and have been present for less than 1 year. When they meet these criteria, the symptoms have a sensitivity for diagnosing early- and late-stage ovarian cancer of 56.7% and 79.5%, respectively.⁴

Sensitivity for the diagnosis of early-stage ovarian cancer may be as high as 80% when the symptom index score is combined with an elevated level of the tumor marker CA 125.³

Transvaginal US is crucial

Transvaginal US is now standard practice to obtain high-resolution images of an adnexal mass. Grayscale US has traditionally been used alone for evaluation.

Specificity is typically lower in women who are premenopausal because many benign lesions, such as endometrioma, have a similar sonographic appearance to cancer.

A number of US scoring algorithms have now been proposed to aid in the triage of women who have an adnexal mass. Sensitivity of these algorithms ranges from 65% to 100%; specificity, from 77% to 95%.⁵

CA 125 is the standard tumor marker

For the past two decades, CA 125 has been the standard serum marker in the screening of high-risk women for ovarian cancer and the triage of women who have an adnexal mass.

This blood test has been studied widely since its introduction in 1983. It typically has sensitivity of 75% to 85% and specificity of 85% to 95% in identifying women who have ovarian cancer. However, it is elevated in only 50% to 60% of women who have stage I ovarian cancer. Its lack of specificity and poor positive predictive value have kept researchers busy trying to identify other serum markers, for both ovarian cancer and identification of high-risk pelvic masses.

Our recommended workup and management of adnexal masses In postmenopausal women who had a pelvic mass, one study found that a CA 125 level above 65 IU/mL had sensitivity of 71% and specificity of 92.5% in the identification of ovarian cancer.⁶ Another group found that CA 125 levels above 65 IU/mL were more than 95% sensitive in the diagnosis of ovarian cancer in postmenopausal women.⁷

Several studies have combined CA 125 with other markers or with US to screen high-risk women or triage those who have an adnexal mass. These studies have shown modest improvements in sensitivity but usually lower specificity than with CA 125 testing alone.

Markers that may be used for suspected sex cord stromas and germ-cell tumors are:

• lactate dehydrogenase (LDH) for dysgerminomas
• alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) for yolk sac tumors
• testosterone for Sertoli-Leydig cell tumors
• inhibin A and B for granulosa cell tumors.

An algorithm for working up and managing adnexal masses appears above.

How to gain abdominal access

In the opening case, the patient clearly has a benign mass. The treatment? Safe entry into the peritoneal cavity to remove the cyst and as little normal tissue as possible. This is critical in this patient because she has only one ovary.

Peritoneal access for abdominal and pelvic laparoscopy has been studied widely. Options include:

• direct insertion using a Veress needle
• open laparoscopy
• direct trocar insertion.

The technique usually depends on the preference of the surgeon. The primary goal of abdominal entry is to minimize the risk of injury, particularly unrecognized injury.

Data on complication rates show no definite benefit for open versus closed techniques in the prevention of injury to underlying viscera. However, evidence does suggest that the open technique may lower the risk of major vascular injury.⁸

We employ direct trocar insertion using radially expanding or optical trocars.

The Veress needle option

When the Veress needle is used to gain intraperitoneal access, data indicate that initial intraperitoneal pressure below 10 mm Hg is a reliable marker for peritoneal entry, even in obese patients.⁹ Insufflation pressure as high as 25 to 30 mm Hg prior to placement of the initial trocar is safe from a cardiopulmonary standpoint and may allow easier entry with a nonbladed trocar.¹⁰

Tests to confirm intraperitoneal placement of the Veress needle, such as the hanging-drop test or saline flush, do not appear to offer any additional useful information.¹¹

Open laparoscopy is suitable when adhesions are unlikely

Open laparoscopy is typically performed by making a minilaparotomy incision at the umbilicus and then dissecting and entering the peritoneal cavity. A blunt-tip trocar is inserted.

The disadvantage of this approach is that there may be extensive adhesions under the umbilicus, and it is difficult to dissect such adhesions sufficiently to introduce a cannula and laparoscope. Adhesions left behind often obscure the field of view after introduction of the trocar.

Our preference? Left upper-quadrant insertion

In Case 1, the previous midline incision mandates an alternative approach. When abdominal entry at the umbilicus is unsuccessful or potentially difficult because of an earlier midline incision, umbilical hernia repair, or history of multiple lower abdominal or pelvic surgeries, a left upper-quadrant insertion is useful. It is, in fact, our preferred technique, and involves a small incision at the midclavicular line 5 cm below the left costal margin, at a site called Palmer’s point.

The direction of insertion usually ranges from 45° to 90°, depending on the patient’s body weight. If the trocar is placed properly, the closest organs are the stomach and the left lobe of the liver (4 to 6 cm).¹² Given the stomach’s close proximity, it should be decompressed with an orogastric tube prior to trocar insertion.

Several studies have demonstrated the safety and efficacy of this entry technique.^12-14 It can be helpful in cases that involve difficult access. We usually use a 5-mm primary trocar site for a 5-mm laparoscope. Modern optics allow for a pristine view with these small scopes, eliminating the need to close fascia and perhaps causing less pain at the incision.

Accessory trocar sites facilitate complex technique

We usually use three accessory sites. Two of them are lower-quadrant ports that are placed 2 cm medial and 2 cm cephalad to the anterior superior iliac spine. This area generally lies well away from the inferior epigastric vessels and remains above the area of the ilioinguinal and iliohypogastric nerves, making it a safer point of insertion.¹⁵ One trocar is 5 mm in size and the other is 10 mm. The larger one is used to extract the specimen.

We place an additional 5-mm port lateral to the rectus muscle at the level of the umbilicus. This allows the principal surgeon to use two instruments (a toothed forceps and scissors) comfortably while the assistant holds the laparoscope and assists with a grasper.

Does the type of trocar matter?

No randomized studies have directly compared all types of trocars. Options include:

• a pyramidal tip (as in reusable trocars) or shielded tip
• radial expansion
• visible entry
• blunt (Hasson-type) trocar.

Safety data on direct comparison of trocars are limited, but it appears that a radially expanding trocar may offer less port-site pain and potentially less bleeding than a traditional cutting trocar.¹⁶ Moreover, the rate of hernia at the port site appears to be relatively low with a radially expanding trocar, even when fascia is left unclosed at a 10-mm site.¹⁷

None of these trocars appears to be clearly superior at avoiding visceral or vascular injury.

Technique of laparoscopic cyst removal

A video clip of the surgery is linked to this article in the Video Library at www.obgmanagement.com. In this case, a trocar was inserted in the left upper quadrant, and a laparoscopic cystectomy was initiated using the trocars already specified.

The peritoneal cavity and adnexa were inspected, followed by pelvic washings, as detailed in TABLE 2 . Next, the ovarian cortex was incised ( FIGURE 1A ) with scissors using bipolar or unipolar energy, typically at a low power setting, such as 12 to 15 watts.

It was relatively easy to develop a tissue plane between the cortex and underlying dermoid cyst using simple or aqua-dissection ( FIGURE 1B and C ). The cyst was enucleated without rupture and inserted into a specimen bag through a 10-mm port ( FIGURE 1D ). (The specimen bags generally are available in 10-mm and 15-mm sizes.) Once the trocar was removed, the entire specimen was brought out through the incision ( FIGURE 1E ).

Cystic masses can generally be carefully aspirated using a laparoscopic needle or angiocath, or they can be incised and drained using a standard suction device. Manufacturers of most specimen bags do not recommend the morcellation of tissue within the bag because of the potential for rupture of the bag with tumor spillage or injury to underlying structures.

Occasionally, the mass remains too large to remove after drainage of the cyst fluid. Remedies include enlarging the port site with a scalpel or using a gallbladder speculum to increase the diameter of the port site ( FIGURE 1E ). If possible, the incision should be large enough to deliver the entire bag intact. Use of excessive force will rupture the bag and may cause the specimen to be lost or malignant cells to be inadvertently spilled (in the case of a cancer diagnosis).

TABLE 2

Take these 10 steps to safe laparoscopic surgery

FIGURE 1 Laparoscopic cyst removal

Begin by incising the cortex using scissors with or without an energy source.

Dissect the cyst free from the cortex using sharp dissection.

Remove the cyst from the ovary.

Place the cyst in a specimen bag, and …

… bring it to the surface for extraction. The abdominal incision may have to be enlarged to accommodate the specimen.

CASE 1: OUTCOME

The patient’s cyst is removed intact and she is discharged home. Rupture of a dermoid cyst is not associated with any problems as long as copious irrigation is used to aspirate the cyst content.¹⁸ Other cysts, such as endometriomas, may not be as easily dissected, and rupture is inevitable.

CASE 2: Symptoms suggestive of cancer

Mrs. B is a 47-year-old woman who reports abdominal bloating for the past 3 weeks. She also complains of early satiety and occasional constipation. She has no history of cancer, but her sister was given a diagnosis of breast cancer at 41 years of age, and her maternal aunt had breast cancer at 55 years.

Mrs. B is moderately obese, with a nontender abdomen and no palpable mass. Her pelvic exam also is negative for a mass or nodularity, but the extent of the exam is limited by body habitus. Her physician orders a transvaginal US, which reveals a 6-cm complex mass with thin septation and a 1-cm solid nodule, with no definite blood flow. The patient’s CA 125 level is 80 IU/mL, which we consider to be within the low-risk range for a premenopausal woman.

The patient is counseled about the need to have the mass removed and is scheduled for laparoscopic right salpingooophorectomy. Given the family history of breast cancer, the physician also requests consultation with a gynecologic oncologist, who agrees to assist with surgery and perform a laparotomy and staging in the event that a malignancy is diagnosed.

Is the mass likely to be malignant?

Given the patient’s family history of breast cancer, the recent onset of symptoms associated with ovarian cancer,² and the characteristics of the mass (complex, with a nodule), malignancy is possible. This patient has an intermediate risk of cancer and requires additional counseling and planning.

However, most women who undergo laparoscopy for removal of an adnexal mass have benign pathologic findings.

What is the real risk of ovarian cancer?

The lifetime risk of developing ovarian cancer in the general population remains stable at approximately 1 in 70 women, with a mean age at diagnosis of 63 years.¹⁹ Ninety percent of ovarian cancer cases are sporadic, and less than 10% can be linked to genetic syndromes.

Women who have mutations in the BRCA1 gene carry a lifetime risk of ovarian cancer of up to 50%, and women who have mutations in BRCA2 have a lifetime risk of up to 25%.^20,21 Women who have mutations associated with Lynch II syndrome or Hereditary Nonpolyposis Colorectal Cancer syndrome may have a lifetime risk of ovarian cancer of 12%.^22,23

Some women who have a strong family history of breast and ovarian cancer do not carry a known mutation, but are likely to be at increased risk.

Additional risk factors known to be associated with ovarian cancer are nulliparity and infertility. However, the single most important risk factor for epithelial ovarian cancer is age.

Risk-reducing strategies include:

• screening
• prophylactic bilateral salpingooophorectomy (PBSO)
• use of oral contraceptives.^20,24-26

In the case of PBSO, it is imperative to ensure that all ovarian surface epithelium is removed. This means excising the infundibulopelvic ligament at least 1.5 cm above the proximal end of the ovary and excising any adjacent tissue to which the ovary is adherent (including pelvic sidewall peritoneum). Both requirements are easily achieved using the techniques outlined here.

Who should perform surgery?

The American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Oncologists (SGO) have published guidelines for referral to a gynecologic oncologist ( TABLE 3 ). When Im and colleagues reviewed the records of more than 1,000 women who underwent surgery for a pelvic mass at six institutions over 12 months, they found that 70% of premenopausal women and 94% of postmenopausal women who were diagnosed with ovarian cancer were properly referred to a qualified subspecialist.²⁷ “Over”-referral occurred in 30% to 40% of women who had a benign mass, but may be preferable given the importance of proper staging and debulking to survival.

ACOG and the SGO recommend referral for women who have:

• elevated tumor markers
• ascites
• a fixed or nodular mass
• a strong family history of breast or ovarian cancer.

Consider preoperative referral of all high-risk and, probably, intermediate-risk women, depending on the availability of qualified specialists for complete surgical staging.

In addition, women need to be counseled thoroughly about the possibility that a malignancy will be diagnosed by frozen section, necessitating additional surgical procedures.

TABLE 3

Your patient has a newly diagnosed pelvic mass. Should you refer her?

Technique of laparoscopic adnexectomy

In Case 2, an umbilical site was chosen for the primary cannula. In general, the direction of insertion depends on the patient’s body habitus. Heavier patients have a thicker abdominal wall and an umbilicus below the level of the aortic bifurcation. In these women, the angle of insertion should be adjusted from the usual 45° (for patients of normal weight) to an angle nearer to 90°. Lateral ports are typical, as in Case 1.

Treat every mass like cancer

Laparoscopic excision of an adnexal mass can be safe and effective, with better outcomes and recovery than with laparotomy, provided the surgeon adheres to basic principles ( TABLE 2 ). This means treating every mass as though it is potentially malignant, and thoroughly inspecting the abdominal cavity before and after excision of the mass.

Know the retroperitoneal space

As with Case 1, successful laparoscopic excision of an adnexal mass begins with inspection of the peritoneal cavity, abdominopelvic washings, and identification of both the infundibulopelvic ligament and ureter. Knowledge of the retroperitoneal space can be of great value in difficult cases that involve significant pelvic adhesions or sidewall fibrosis. We generally use a retroperitoneal approach for laparoscopic adnexectomy ( FIGURE 2A ).

In our typical approach, we incise the peritoneum lateral to the uteroovarian ligament and continue the incision up the pelvic sidewall lateral to the infundibulopelvic ligament and up along the paracolic gutter, if needed ( FIGURE 2A ). We then mobilize the medial leaf of the broad ligament from the sidewall using blunt dissection between the external iliac vessels laterally and the ureter medially ( FIGURE 2B ).

Once we have identified the ureter, we use scissors to create a window in the medial leaf of the broad ligament just beneath the gonadal vessels. We then use an energy source to occlude and transect the pedicle. Using this technique, we secure the infundibulopelvic ligaments and safely mobilize the ureter before initiating more aggressive sidewall dissection distally for adhesions or fibrosis.

Once the ureter is mobilized, we excise the involved peritoneum along with the mass. We then seal and transect the uteroovarian ligament.

FIGURE 2 The retroperitoneal approach

Grasp and incise the peritoneum just lateral to the adnexal mass and enter the retroperitoneal space, where loose areolar tissue is visible, with the ureter seen on the medial leaf of the broad ligament.

After dissecting this tissue, identify the ureter and internal iliac vessels.

Remove the mass in a bag

Once the mass is excised, we place it in a laparoscopic bag, as described for Case 1. Solid adnexal masses are problematic because they are not amenable to drainage, and morcellation is usually discouraged. Laparoscopic excision can still be carried out, and a minilaparotomy or posterior colpotomy can be used to extract the mass in a bag. Patients managed in this way still have a complication rate similar to or lower than that of patients undergoing laparotomy for oophorectomy; they also recover faster.

Risks in cases of malignancy

The risk of tumor spillage in laparoscopic surgery can be lowered using laparoscopically guided minilaparotomy techniques. Preoperative rupture appears to be more predictive of outcome.²⁸

The concern about metastatic implants in a laparoscopic port site in patients who have gynecologic cancer is real, with an incidence ranging from 0.97% to 1.1%. The phenomenon usually affects women who had ovarian cancer and is most common after laparoscopy with findings of ascites, carcinomatosis, or persistent disease (in the case of second-look laparoscopy performed after completion of primary therapy for ovarian cancer).

These data suggest that port-site implantation is not a concern that should deter clinicians from laparoscopic evaluation of a suspected ovarian neoplasm unless a patient presents with ascites or carcinomatosis suggestive of advanced disease.²⁹

Data are limited regarding delays in definitive therapy. One study suggests that definitive staging on the day of rupture does not influence overall outcome, but delay by more than 2 weeks may lead to poorer prognosis.³⁰

CASE 2: OUTCOME

Laparoscopy is performed. On initial inspection, the peritoneal cavity is unremarkable. The right ovary is multicystic with normal surface anatomy. The mass is somewhat adherent to the pelvic sidewall. Adnexectomy is performed, and frozen section reveals the mass to be a serous cystadenoma.

The authors report no financial relationships relevant to this article.

CASE 1: Cystic mass in patient’s only remaining ovary

Mrs. R is a 29-year-old G1P1 who underwent a right oophorectomy, with a midline incision, for a dermoid cyst at the time of cesarean delivery. She now has a left ovarian cyst. Preoperative ultrasonography (US) reveals that it measures 3.5×4.2×3.7 cm and has both solid components and a multiloculated appearance, consistent with a dermoid cyst.

How common is this scenario?

Studies predict that one of every three women will undergo surgical management of an adnexal mass at some point in her life.¹ This troubling statistic prompts several critical questions:

• How do we handle the workup for these women so that only appropriate patients undergo surgery?
• How often will a mass be malignant?
• How can we safely remove an adnexal mass to maximize patient safety, reduce overall recovery time, and prevent less favorable outcomes in women who are eventually found to have a malignancy?

A thorough workup and, sometimes, conservative management can prevent unnecessary surgery that may lead to early menopause or surgical complications. And maximizing the use of minimally invasive techniques in women who do require surgery can shorten hospital stay and recovery time. At the time of surgery, careful abdominal entry and meticulous surgical dissection and mass removal can limit the potential risks of laparoscopic excision in women who have an ultimate diagnosis of cancer.

In this article, we review the workup for women who have an adnexal mass, describe patient-selection criteria for laparoscopic surgery, including the risks and benefits of this approach ( TABLE 1 ), and present several techniques to safely manage a mass with potentially malignant histology via laparoscopy.

TABLE 1

There are benefits and risks to managing an adnexal mass laparoscopically

Begin with the physical

When a woman is known to have a pelvic mass, the aim of the office exam is to 1) identify characteristics that suggest malignancy and 2) rule out nongynecologic causes of the mass. Physical findings that are worrisome for a malignant process include:

• fixed or nodular pelvic mass
• bilateral masses
• nodular abdominal mass
• ascites
• pleural effusion on auscultation or percussion of the lung.

Although these findings can be present under benign conditions, they increase the risk that a malignancy will be detected at surgery.

Other causes of a pelvic mass should also be considered, including infection (pelvic abscess) and tumors of the colon, particularly when the pelvic mass occurs on the left side.

Some symptoms, though vague, are worth noting

Although ovarian cancer was once thought to be a silent disease, recent research has shown that bloating, pelvic or abdominal pain, early satiety, and urinary frequency and urgency are more common among women with ovarian cancer than among healthy controls and patients in high-risk screening clinics.^2-4 Although these symptoms are generally nonspecific, they merit attention if they occur more than 12 times a month and have been present for less than 1 year. When they meet these criteria, the symptoms have a sensitivity for diagnosing early- and late-stage ovarian cancer of 56.7% and 79.5%, respectively.⁴

Sensitivity for the diagnosis of early-stage ovarian cancer may be as high as 80% when the symptom index score is combined with an elevated level of the tumor marker CA 125.³

Transvaginal US is crucial

Transvaginal US is now standard practice to obtain high-resolution images of an adnexal mass. Grayscale US has traditionally been used alone for evaluation.

Specificity is typically lower in women who are premenopausal because many benign lesions, such as endometrioma, have a similar sonographic appearance to cancer.

A number of US scoring algorithms have now been proposed to aid in the triage of women who have an adnexal mass. Sensitivity of these algorithms ranges from 65% to 100%; specificity, from 77% to 95%.⁵

CA 125 is the standard tumor marker

For the past two decades, CA 125 has been the standard serum marker in the screening of high-risk women for ovarian cancer and the triage of women who have an adnexal mass.

This blood test has been studied widely since its introduction in 1983. It typically has sensitivity of 75% to 85% and specificity of 85% to 95% in identifying women who have ovarian cancer. However, it is elevated in only 50% to 60% of women who have stage I ovarian cancer. Its lack of specificity and poor positive predictive value have kept researchers busy trying to identify other serum markers, for both ovarian cancer and identification of high-risk pelvic masses.

Our recommended workup and management of adnexal masses In postmenopausal women who had a pelvic mass, one study found that a CA 125 level above 65 IU/mL had sensitivity of 71% and specificity of 92.5% in the identification of ovarian cancer.⁶ Another group found that CA 125 levels above 65 IU/mL were more than 95% sensitive in the diagnosis of ovarian cancer in postmenopausal women.⁷

Several studies have combined CA 125 with other markers or with US to screen high-risk women or triage those who have an adnexal mass. These studies have shown modest improvements in sensitivity but usually lower specificity than with CA 125 testing alone.

Markers that may be used for suspected sex cord stromas and germ-cell tumors are:

• lactate dehydrogenase (LDH) for dysgerminomas
• alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) for yolk sac tumors
• testosterone for Sertoli-Leydig cell tumors
• inhibin A and B for granulosa cell tumors.

An algorithm for working up and managing adnexal masses appears above.

How to gain abdominal access

In the opening case, the patient clearly has a benign mass. The treatment? Safe entry into the peritoneal cavity to remove the cyst and as little normal tissue as possible. This is critical in this patient because she has only one ovary.

Peritoneal access for abdominal and pelvic laparoscopy has been studied widely. Options include:

• direct insertion using a Veress needle
• open laparoscopy
• direct trocar insertion.

The technique usually depends on the preference of the surgeon. The primary goal of abdominal entry is to minimize the risk of injury, particularly unrecognized injury.

Data on complication rates show no definite benefit for open versus closed techniques in the prevention of injury to underlying viscera. However, evidence does suggest that the open technique may lower the risk of major vascular injury.⁸

We employ direct trocar insertion using radially expanding or optical trocars.

The Veress needle option

When the Veress needle is used to gain intraperitoneal access, data indicate that initial intraperitoneal pressure below 10 mm Hg is a reliable marker for peritoneal entry, even in obese patients.⁹ Insufflation pressure as high as 25 to 30 mm Hg prior to placement of the initial trocar is safe from a cardiopulmonary standpoint and may allow easier entry with a nonbladed trocar.¹⁰

Tests to confirm intraperitoneal placement of the Veress needle, such as the hanging-drop test or saline flush, do not appear to offer any additional useful information.¹¹

Open laparoscopy is suitable when adhesions are unlikely

Open laparoscopy is typically performed by making a minilaparotomy incision at the umbilicus and then dissecting and entering the peritoneal cavity. A blunt-tip trocar is inserted.

The disadvantage of this approach is that there may be extensive adhesions under the umbilicus, and it is difficult to dissect such adhesions sufficiently to introduce a cannula and laparoscope. Adhesions left behind often obscure the field of view after introduction of the trocar.

Our preference? Left upper-quadrant insertion

In Case 1, the previous midline incision mandates an alternative approach. When abdominal entry at the umbilicus is unsuccessful or potentially difficult because of an earlier midline incision, umbilical hernia repair, or history of multiple lower abdominal or pelvic surgeries, a left upper-quadrant insertion is useful. It is, in fact, our preferred technique, and involves a small incision at the midclavicular line 5 cm below the left costal margin, at a site called Palmer’s point.

The direction of insertion usually ranges from 45° to 90°, depending on the patient’s body weight. If the trocar is placed properly, the closest organs are the stomach and the left lobe of the liver (4 to 6 cm).¹² Given the stomach’s close proximity, it should be decompressed with an orogastric tube prior to trocar insertion.

Several studies have demonstrated the safety and efficacy of this entry technique.^12-14 It can be helpful in cases that involve difficult access. We usually use a 5-mm primary trocar site for a 5-mm laparoscope. Modern optics allow for a pristine view with these small scopes, eliminating the need to close fascia and perhaps causing less pain at the incision.

Accessory trocar sites facilitate complex technique

We usually use three accessory sites. Two of them are lower-quadrant ports that are placed 2 cm medial and 2 cm cephalad to the anterior superior iliac spine. This area generally lies well away from the inferior epigastric vessels and remains above the area of the ilioinguinal and iliohypogastric nerves, making it a safer point of insertion.¹⁵ One trocar is 5 mm in size and the other is 10 mm. The larger one is used to extract the specimen.

We place an additional 5-mm port lateral to the rectus muscle at the level of the umbilicus. This allows the principal surgeon to use two instruments (a toothed forceps and scissors) comfortably while the assistant holds the laparoscope and assists with a grasper.

Does the type of trocar matter?

No randomized studies have directly compared all types of trocars. Options include:

• a pyramidal tip (as in reusable trocars) or shielded tip
• radial expansion
• visible entry
• blunt (Hasson-type) trocar.

Safety data on direct comparison of trocars are limited, but it appears that a radially expanding trocar may offer less port-site pain and potentially less bleeding than a traditional cutting trocar.¹⁶ Moreover, the rate of hernia at the port site appears to be relatively low with a radially expanding trocar, even when fascia is left unclosed at a 10-mm site.¹⁷

None of these trocars appears to be clearly superior at avoiding visceral or vascular injury.

Technique of laparoscopic cyst removal

A video clip of the surgery is linked to this article in the Video Library at www.obgmanagement.com. In this case, a trocar was inserted in the left upper quadrant, and a laparoscopic cystectomy was initiated using the trocars already specified.

The peritoneal cavity and adnexa were inspected, followed by pelvic washings, as detailed in TABLE 2 . Next, the ovarian cortex was incised ( FIGURE 1A ) with scissors using bipolar or unipolar energy, typically at a low power setting, such as 12 to 15 watts.

It was relatively easy to develop a tissue plane between the cortex and underlying dermoid cyst using simple or aqua-dissection ( FIGURE 1B and C ). The cyst was enucleated without rupture and inserted into a specimen bag through a 10-mm port ( FIGURE 1D ). (The specimen bags generally are available in 10-mm and 15-mm sizes.) Once the trocar was removed, the entire specimen was brought out through the incision ( FIGURE 1E ).

Cystic masses can generally be carefully aspirated using a laparoscopic needle or angiocath, or they can be incised and drained using a standard suction device. Manufacturers of most specimen bags do not recommend the morcellation of tissue within the bag because of the potential for rupture of the bag with tumor spillage or injury to underlying structures.

Occasionally, the mass remains too large to remove after drainage of the cyst fluid. Remedies include enlarging the port site with a scalpel or using a gallbladder speculum to increase the diameter of the port site ( FIGURE 1E ). If possible, the incision should be large enough to deliver the entire bag intact. Use of excessive force will rupture the bag and may cause the specimen to be lost or malignant cells to be inadvertently spilled (in the case of a cancer diagnosis).

TABLE 2

Take these 10 steps to safe laparoscopic surgery

FIGURE 1 Laparoscopic cyst removal

Begin by incising the cortex using scissors with or without an energy source.

Dissect the cyst free from the cortex using sharp dissection.

Remove the cyst from the ovary.

Place the cyst in a specimen bag, and …

… bring it to the surface for extraction. The abdominal incision may have to be enlarged to accommodate the specimen.

CASE 1: OUTCOME

The patient’s cyst is removed intact and she is discharged home. Rupture of a dermoid cyst is not associated with any problems as long as copious irrigation is used to aspirate the cyst content.¹⁸ Other cysts, such as endometriomas, may not be as easily dissected, and rupture is inevitable.

CASE 2: Symptoms suggestive of cancer

Mrs. B is a 47-year-old woman who reports abdominal bloating for the past 3 weeks. She also complains of early satiety and occasional constipation. She has no history of cancer, but her sister was given a diagnosis of breast cancer at 41 years of age, and her maternal aunt had breast cancer at 55 years.

Mrs. B is moderately obese, with a nontender abdomen and no palpable mass. Her pelvic exam also is negative for a mass or nodularity, but the extent of the exam is limited by body habitus. Her physician orders a transvaginal US, which reveals a 6-cm complex mass with thin septation and a 1-cm solid nodule, with no definite blood flow. The patient’s CA 125 level is 80 IU/mL, which we consider to be within the low-risk range for a premenopausal woman.

The patient is counseled about the need to have the mass removed and is scheduled for laparoscopic right salpingooophorectomy. Given the family history of breast cancer, the physician also requests consultation with a gynecologic oncologist, who agrees to assist with surgery and perform a laparotomy and staging in the event that a malignancy is diagnosed.

Is the mass likely to be malignant?

Given the patient’s family history of breast cancer, the recent onset of symptoms associated with ovarian cancer,² and the characteristics of the mass (complex, with a nodule), malignancy is possible. This patient has an intermediate risk of cancer and requires additional counseling and planning.

However, most women who undergo laparoscopy for removal of an adnexal mass have benign pathologic findings.

What is the real risk of ovarian cancer?

The lifetime risk of developing ovarian cancer in the general population remains stable at approximately 1 in 70 women, with a mean age at diagnosis of 63 years.¹⁹ Ninety percent of ovarian cancer cases are sporadic, and less than 10% can be linked to genetic syndromes.

Women who have mutations in the BRCA1 gene carry a lifetime risk of ovarian cancer of up to 50%, and women who have mutations in BRCA2 have a lifetime risk of up to 25%.^20,21 Women who have mutations associated with Lynch II syndrome or Hereditary Nonpolyposis Colorectal Cancer syndrome may have a lifetime risk of ovarian cancer of 12%.^22,23

Some women who have a strong family history of breast and ovarian cancer do not carry a known mutation, but are likely to be at increased risk.

Additional risk factors known to be associated with ovarian cancer are nulliparity and infertility. However, the single most important risk factor for epithelial ovarian cancer is age.

Risk-reducing strategies include:

• screening
• prophylactic bilateral salpingooophorectomy (PBSO)
• use of oral contraceptives.^20,24-26

In the case of PBSO, it is imperative to ensure that all ovarian surface epithelium is removed. This means excising the infundibulopelvic ligament at least 1.5 cm above the proximal end of the ovary and excising any adjacent tissue to which the ovary is adherent (including pelvic sidewall peritoneum). Both requirements are easily achieved using the techniques outlined here.

Who should perform surgery?

The American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Oncologists (SGO) have published guidelines for referral to a gynecologic oncologist ( TABLE 3 ). When Im and colleagues reviewed the records of more than 1,000 women who underwent surgery for a pelvic mass at six institutions over 12 months, they found that 70% of premenopausal women and 94% of postmenopausal women who were diagnosed with ovarian cancer were properly referred to a qualified subspecialist.²⁷ “Over”-referral occurred in 30% to 40% of women who had a benign mass, but may be preferable given the importance of proper staging and debulking to survival.

ACOG and the SGO recommend referral for women who have:

• elevated tumor markers
• ascites
• a fixed or nodular mass
• a strong family history of breast or ovarian cancer.

Consider preoperative referral of all high-risk and, probably, intermediate-risk women, depending on the availability of qualified specialists for complete surgical staging.

In addition, women need to be counseled thoroughly about the possibility that a malignancy will be diagnosed by frozen section, necessitating additional surgical procedures.

TABLE 3

Your patient has a newly diagnosed pelvic mass. Should you refer her?

Technique of laparoscopic adnexectomy

In Case 2, an umbilical site was chosen for the primary cannula. In general, the direction of insertion depends on the patient’s body habitus. Heavier patients have a thicker abdominal wall and an umbilicus below the level of the aortic bifurcation. In these women, the angle of insertion should be adjusted from the usual 45° (for patients of normal weight) to an angle nearer to 90°. Lateral ports are typical, as in Case 1.

Treat every mass like cancer

Laparoscopic excision of an adnexal mass can be safe and effective, with better outcomes and recovery than with laparotomy, provided the surgeon adheres to basic principles ( TABLE 2 ). This means treating every mass as though it is potentially malignant, and thoroughly inspecting the abdominal cavity before and after excision of the mass.

Know the retroperitoneal space

As with Case 1, successful laparoscopic excision of an adnexal mass begins with inspection of the peritoneal cavity, abdominopelvic washings, and identification of both the infundibulopelvic ligament and ureter. Knowledge of the retroperitoneal space can be of great value in difficult cases that involve significant pelvic adhesions or sidewall fibrosis. We generally use a retroperitoneal approach for laparoscopic adnexectomy ( FIGURE 2A ).

In our typical approach, we incise the peritoneum lateral to the uteroovarian ligament and continue the incision up the pelvic sidewall lateral to the infundibulopelvic ligament and up along the paracolic gutter, if needed ( FIGURE 2A ). We then mobilize the medial leaf of the broad ligament from the sidewall using blunt dissection between the external iliac vessels laterally and the ureter medially ( FIGURE 2B ).

Once we have identified the ureter, we use scissors to create a window in the medial leaf of the broad ligament just beneath the gonadal vessels. We then use an energy source to occlude and transect the pedicle. Using this technique, we secure the infundibulopelvic ligaments and safely mobilize the ureter before initiating more aggressive sidewall dissection distally for adhesions or fibrosis.

Once the ureter is mobilized, we excise the involved peritoneum along with the mass. We then seal and transect the uteroovarian ligament.

FIGURE 2 The retroperitoneal approach

Grasp and incise the peritoneum just lateral to the adnexal mass and enter the retroperitoneal space, where loose areolar tissue is visible, with the ureter seen on the medial leaf of the broad ligament.

After dissecting this tissue, identify the ureter and internal iliac vessels.

Remove the mass in a bag

Once the mass is excised, we place it in a laparoscopic bag, as described for Case 1. Solid adnexal masses are problematic because they are not amenable to drainage, and morcellation is usually discouraged. Laparoscopic excision can still be carried out, and a minilaparotomy or posterior colpotomy can be used to extract the mass in a bag. Patients managed in this way still have a complication rate similar to or lower than that of patients undergoing laparotomy for oophorectomy; they also recover faster.

Risks in cases of malignancy

The risk of tumor spillage in laparoscopic surgery can be lowered using laparoscopically guided minilaparotomy techniques. Preoperative rupture appears to be more predictive of outcome.²⁸

The concern about metastatic implants in a laparoscopic port site in patients who have gynecologic cancer is real, with an incidence ranging from 0.97% to 1.1%. The phenomenon usually affects women who had ovarian cancer and is most common after laparoscopy with findings of ascites, carcinomatosis, or persistent disease (in the case of second-look laparoscopy performed after completion of primary therapy for ovarian cancer).

These data suggest that port-site implantation is not a concern that should deter clinicians from laparoscopic evaluation of a suspected ovarian neoplasm unless a patient presents with ascites or carcinomatosis suggestive of advanced disease.²⁹

Data are limited regarding delays in definitive therapy. One study suggests that definitive staging on the day of rupture does not influence overall outcome, but delay by more than 2 weeks may lead to poorer prognosis.³⁰

CASE 2: OUTCOME

Laparoscopy is performed. On initial inspection, the peritoneal cavity is unremarkable. The right ovary is multicystic with normal surface anatomy. The mass is somewhat adherent to the pelvic sidewall. Adnexectomy is performed, and frozen section reveals the mass to be a serous cystadenoma.

Comment on this article

Jason, age 16, has had difficulty with sleep initiation for 2 years. He describes going to bed at 10:30 PM on school nights but falling asleep no sooner than midnight and typically after 1:30 AM. He denies contributions from an “active mind” or environmental disturbances, and his bedroom contains no TV, computer, or other media devices. He does not sleep better with a change in environment. He denies pervasive low mood symptoms and believes his mood hinges predominantly on his ability to achieve sufficient sleep.

Once asleep, Jason generally enjoys good sleep consolidation until he needs to arise at 6:30 AM. His mother awakens him with difficulty, as he often sleeps through his alarm. He sleeps approximately 5 hours nightly during the school week, endorses impaired concentration, and often dozes during his first several classes. When he returns home from school, he finds it very difficult to resist napping.

On weekends he retires at 1 AM or later and typically falls asleep within 30 minutes. He usually awakens at noon but can sleep as late as 4:30 PM. He feels slightly more refreshed on weekends and describes his mood then as improved. During a recent spring break, he felt much better when allowed to sleep as much as he wanted.

Delayed sleep phase disorder (DSPD)—characterized by a pathological “night owl” circadian preference—is seen most commonly in adolescents and is associated with psychiatric morbidity, psychosocial impairment, and poor academic performance. Proper identification of the condition can be enhanced with a variety of assessment tools, and successful treatment requires an awareness of potential endogenous and exogenous contributors.

This article describes what is known about DSPD and uses the case example to illustrate diagnostic assessment and treatment choices. Intriguing data support various pathophysiologic explanations for DSPD (Box 1).^1-6 Facilitating the adjustment of patients’ physiologic clocks is the overall goal in managing DSPD.

Box 1

Extreme ‘eveningness’

Because of their extreme seemingly innate preference to retire and arise at relatively late clock hours (an “eveningness” trait), school-aged patients with DSPD represent a high-risk population for problematic sleepiness. In a survey of 612 high school students, the 63% who felt they needed more sleep on school nights showed a strong eveningness preference (as assessed by questionnaire), compared with students who described getting sufficient sleep.⁷ Other studies have revealed psychiatric morbidity (including affective and personality disorders), psychosocial impairment, and poor academic performance associated with the condition.^8-10

DSPD may affect 7% to 16% of patients presenting with insomnia complaints in sleep medicine clinics.¹¹ The condition appears most common among young cohorts and has been reported to affect up to 7% of adolescents in the United States.¹² Its high frequency in this age group may be a pathologic exaggeration of the normal tendency toward delayed timing of sleep and wakefulness linked with pubertal development.¹³

Sleep and wakefulness regulation

Conceptually, 2 processes govern sleep and wakefulness:

• The homeostatic drive to sleep (process S) is proportional to the duration of sleep restriction and becomes maximal at about 40 hours.
• Circadian regulation (process C) creates a drive for wakefulness that variably opposes process S and depends upon intrinsic rhythms.¹⁴

Neurons of the suprachiasmatic nucleus in the hypothalamus exert master coordination of this sleep/wake rhythm, along with other behavioral and physiologic variables.¹⁵ Because the typical intrinsic period is slightly longer than 24 hours, synchronization to the 24-hour day (entrainment) is accomplished by environmental inputs (zeitgebers, or “time givers”), the most important of which is exposure to light.¹⁶

Misalignment between endogenous circadian rhythms and the light/dark cycle can result in circadian rhythm sleep disorders, such as:

• delayed sleep timing (DSPD)
• advanced sleep timing (advanced sleep phase disorder)
• erratic sleep timing (irregular sleep/wake rhythm)
• complete dissociation from the light/dark cycle (circadian rhythm sleep disorder, free-running type).

These 4 conditions are thought to involve predominantly intrinsic mechanisms, but circadian dysrhythmias also can be induced by exogenous factors. Extreme work schedules or rapid travel across time zones can challenge the circadian system’s ability to acclimate and the individual’s ability to achieve a desired sleep schedule.¹⁷

Differential diagnosis

Because DSPD relates primarily to an aberration in timing of sleep, it is characterized as a disorder only if the individual’s preferred schedule interferes substantially with social or occupational functioning. The International Classification of Sleep Disorders (ICSD) provides detailed diagnostic criteria (Table).¹⁷

Table

Diagnostic criteria for delayed sleep phase disorder

Depression and anxiety often manifest with sleep difficulties, as do inadequate sleep hygiene and other conditions associated with prolonged sleep initiation. According to ICSD criteria, primary insomnia can be differentiated from DSPD if the patient readily initiates and maintains sleep when allowed to sleep on his/her desired sleep/wake schedule. Accumulated evidence has largely debunked this notion, however, as polysomnographic studies have demonstrated both prolonged sleep latency and impaired sleep efficiency in DSPD patients versus matched controls.³

Assessment tools can complement the clinical history in diagnosing DSPD. Either a sleep log or actigraphy is required to demonstrate a stable phase delay, but actigraphy typically generates more reliable data.¹⁸ Actigraphs are compact “motion detectors” whose output while being worn by patients allows longitudinal assessment of sleep/wake parameters.

Eveningness tendencies of presumptive DSPD patients can be further verified with the Morningness-Eveningness Questionnaire (MEQ) (Box 2).¹⁹ Low scores are associated with evening types—felt to correspond to the endogenous circadian period—and can help narrow the differential diagnosis of sleep-initiation complaints.²⁰

Box 2

CASE CONTINUED: ‘Definite evening type’

Jason scores 28 on the MEQ, consistent with a “definite evening type.” Actigraphic monitoring is scheduled during a school holiday, when he is instructed to sleep according to his preferred schedule with the least possible restriction.

A clearly delayed sleep phase is evident, with the habitual sleep period occurring between 5 AM and 1 PM. Even on days when he was quite sleep-restricted because of an enforced wake time, sleep onset on the ensuing evening was substantially delayed, suggesting an obligate nature for the delayed sleep/wake schedule. Overall, Jason had few complaints with respect to impaired alertness while on this unrestricted schedule and experienced a much more stable mood.

Interventions

Without physiologic assessments, understanding the patient’s “natural” sleep schedule can allow for rational recommendations about using phototherapy and oral melatonin (Figure²¹). However, referral to a sleep specialist is required unless the general psychiatrist has experience in treating circadian rhythm sleep disorders.

Morning phototherapy. Properly timed morning bright light therapy (≥2,500 lux) has been shown to help DSPD patients achieve physiologically measured sleep phase advances, objective improvements in daytime alertness, and earlier reported bedtimes compared with controls.²² Unfortunately, the described 2-hour treatment duration make this research protocol clinically impractical, and most clinicians commence with a 30-minute duration of therapy, as described in the seasonal affective disorder literature.

Relatively new and widely available blue light boxes have been reported to exhibit at least equivalent efficacy to bright light devices (as reported in the literature pertaining to seasonal affective disorder), but with markedly decreased light intensity and fewer associated adverse effects.²³ As the research addressing their use in the treatment of circadian rhythm sleep disorders is still emerging, their future role remains uncertain.

Precautions. Most psychiatrists would not perform a physiologic determination of a patient’s circadian phase, and further undesired phase delays can occur if phototherapy is administered before the core body temperature minimum (Tmin).²⁴ Also, use caution if prescribing phototherapy to patients taking photosensitizing drugs and/or those with ocular or retinal pathology.²⁰

Evening light avoidance. Whether or not you prescribe morning phototherapy, recommending that DSPD patients avoid evening light is essential to avoid further induction or exacerbation of phase delays. Protective eyewear is warranted in instances where these advisory precautions are insufficient (see Related Resources). Such an intervention has been shown effective in decreasing light exposure and undesired phase advances in studies involving subjects exposed to simulated shift work.²⁵

Oral melatonin. Abundant evidence supports melatonin use in achieving phase advances in individuals with DSPD.^26,27 A synergistic effect can be obtained when melatonin is combined with phototherapy.²⁸

Proper timing of melatonin to achieve a maximal phase advance can be estimated based on the individual’s dim light melatonin onset (DLMO), which occurs approximately 14 hours after the habitual (unrestricted) wake time.²⁹ Maximal phase advances appear to occur when melatonin is given approximately 6 hours before the DLMO.²⁶ Thus, a rational practice is to recommend that patients take melatonin 8 hours after their natural wake time. Doses of ≤0.5 mg appear to achieve the maximal chronobiotic effect while avoiding an undesired hypnotic effect.³⁰

Precautions. Verifying the purity of over-the-counter melatonin is difficult. A review by the National Academy of Sciences states that short-term use of melatonin, ≤10 mg/d, appears to be safe in healthy adults but recommends caution in children/adolescents and women of reproductive age. Doses recommended for circadian-based interventions are typically physiologic in nature (i.e., ≤0.5 mg), which may serve to mitigate these concerns.

Adverse effects such as headaches, somnolence, hypotension, hypertension, gastrointestinal upset, and exacerbation of alopecia areata have been reported at higher melatonin doses in healthy adults and at lower doses in persons with preexisting central nervous system, cardiovascular, gastrointestinal, or dermatologic conditions.³¹

Figure Light and melatonin phase response curves: Normal vs. delayed

This schematic compares ‘normal sleep’ phase response curves (PRCs) to light and exogenous melatonin with postulated PRCs for an individual with delayed sleep phase disorder (DSPD), presumed to be 5 hours ‘out of phase.’ Y-axis shows the direction and relative magnitude of phase shifts produced by light or melatonin at times shown on the x-axis. X-axis covers >24 hours to better illustrate the PRCs.
Relationships between ‘normal sleepers’ and DSPD patients are depicted by:

• rectangles (sleep period)
• triangles (core body temperature minimum [Tmin])
• arrows (dim light melatonin onsets [DLMOs]).

‘Normal’ sleep is shown to occur from midnight to 8 AM, and the DSPD patient’s sleep from 5 AM to 1 PM; DLMO and Tmin are similarly delayed by 5 hours in the DSPD patient. This schematic assumes that phase relationships are maintained in DSPD patients, which is not a certainty.
Source: Adapted from reference 21

CASE CONTINUED: Under the bright lights

Jason starts phototherapy treatment during his winter break, administering bright light daily upon natural awakening using a 10,000 lux light box for at least 30 minutes. As instructed, he gradually advances the time of administration by approximately 30 minutes every other day, striving for a nocturnal sleep period of 11 PM to 7 AM. He also wears protective eyewear to reduce light exposure during evening hours to avoid further delays in sleep phase. To further promote a phase advance, he takes oral melatonin, 0.5 mg/d at approximately 8 PM, as determined by his self-report and results of actigraphic recording.

Other options

Hypnotics. Little evidence supports the use of hypnotics in DSPD,³² and patients may show resistance to these drugs.³³ Nevertheless, hypnotics can heighten confidence in the ability to initiate sleep in individuals with a concomitant conditioned insomnia.

With chronotherapy, patients are prescribed a sleep schedule that is delayed several hours incrementally until sleep is aligned to a target bedtime. The individual then is advised to rigorously maintain a regular sleep/wake schedule, repeating the process as necessary.

Although case reports have shown positive results with chronotherapy for DSPD,³⁴ no controlled trials have demonstrated its efficacy or safety. One study reported high relapse rates,³¹ and 1 patient with DSPD developed free-running circadian rhythms.³⁵ Clinical experience suggests chronotherapy is impractical for patients who must adhere to a fixed schedule.

Behavioral approaches

For an adolescent with DSPD, consider asking the school district to allow him or her a later school start-time. This alone often can substantially increase total sleep time and mitigate associated impairments.³⁶ In all instances pursue and address external contributors to DSPD, such as poor sleep hygiene (including excessive caffeine use) and substance misuse.

Emphasize regular wake times, as arising later on weekends can cause phase delays.³⁷ DSPD patients may have a concomitant conditioned insomnia that responds to evidence-based behavioral treatments.³⁸

Whatever intervention you choose, schedule a follow-up appointment in approximately 2 months to evaluate patients’ progress and compliance. Encourage them to contact you with questions or concerns in the interim. Review sleep logs or actigraphy during this visit, and adjust the timing and/or nature of interventions as needed. Adolescents can be particularly noncompliant with clinical interventions, and therapeutic goals cannot be reached without their full investment.

Because no guidelines exist on how long to treat DSPD, stop on a “trial-and-error” basis when symptoms are controlled, and resume if they recur. Another approach is to maintain a desired sleep/wake schedule with bedtime melatonin and encourage continued adherence to other measures.

CASE CONTINUED: Maintenance therapy

Jason returns to the clinic approximately 10 weeks later. After an obviously concerted effort to adhere to treatment, his progress is quite remarkable. He rarely falls asleep later than 11 PM, so he is obtaining 2.5 hours more sleep each night before arising for school at 6:30 AM. Sleepiness at school is rarely problematic, and his mood is more stable.

He nevertheless describes a persistent tendency to retire and arise later and asks to continue melatonin and phototherapy. Because no guidelines exist for long-term therapy of DSPD, he is advised to switch melatonin to bedtime dosing (with a presumed phase-neutral “maintenance” effect), and to continue phototherapy as prescribed.

Related resources

• Wyatt JK. Delayed sleep phase syndrome: pathophysiology and treatment options. Sleep. 2004;27(6):1195-1203.
• Crowley SJ, Acebo C, Carskadon MA. Sleep, circadian rhythms, and delayed sleep phase in adolescence. Sleep Med. 2007;8(6):602-612.
• National Sleep Foundation. Adolescent sleep needs and patterns: research report and resource guide. Washington, DC; 2000:1-30.
• Products designed to assist in the avoidance of light at improper times. www.lowbluelights.com.

Disclosure

Dr. Auger reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Comment on this article

Jason, age 16, has had difficulty with sleep initiation for 2 years. He describes going to bed at 10:30 PM on school nights but falling asleep no sooner than midnight and typically after 1:30 AM. He denies contributions from an “active mind” or environmental disturbances, and his bedroom contains no TV, computer, or other media devices. He does not sleep better with a change in environment. He denies pervasive low mood symptoms and believes his mood hinges predominantly on his ability to achieve sufficient sleep.

Once asleep, Jason generally enjoys good sleep consolidation until he needs to arise at 6:30 AM. His mother awakens him with difficulty, as he often sleeps through his alarm. He sleeps approximately 5 hours nightly during the school week, endorses impaired concentration, and often dozes during his first several classes. When he returns home from school, he finds it very difficult to resist napping.

On weekends he retires at 1 AM or later and typically falls asleep within 30 minutes. He usually awakens at noon but can sleep as late as 4:30 PM. He feels slightly more refreshed on weekends and describes his mood then as improved. During a recent spring break, he felt much better when allowed to sleep as much as he wanted.

Delayed sleep phase disorder (DSPD)—characterized by a pathological “night owl” circadian preference—is seen most commonly in adolescents and is associated with psychiatric morbidity, psychosocial impairment, and poor academic performance. Proper identification of the condition can be enhanced with a variety of assessment tools, and successful treatment requires an awareness of potential endogenous and exogenous contributors.

This article describes what is known about DSPD and uses the case example to illustrate diagnostic assessment and treatment choices. Intriguing data support various pathophysiologic explanations for DSPD (Box 1).^1-6 Facilitating the adjustment of patients’ physiologic clocks is the overall goal in managing DSPD.

Box 1

Extreme ‘eveningness’

Because of their extreme seemingly innate preference to retire and arise at relatively late clock hours (an “eveningness” trait), school-aged patients with DSPD represent a high-risk population for problematic sleepiness. In a survey of 612 high school students, the 63% who felt they needed more sleep on school nights showed a strong eveningness preference (as assessed by questionnaire), compared with students who described getting sufficient sleep.⁷ Other studies have revealed psychiatric morbidity (including affective and personality disorders), psychosocial impairment, and poor academic performance associated with the condition.^8-10

DSPD may affect 7% to 16% of patients presenting with insomnia complaints in sleep medicine clinics.¹¹ The condition appears most common among young cohorts and has been reported to affect up to 7% of adolescents in the United States.¹² Its high frequency in this age group may be a pathologic exaggeration of the normal tendency toward delayed timing of sleep and wakefulness linked with pubertal development.¹³

Sleep and wakefulness regulation

Conceptually, 2 processes govern sleep and wakefulness:

• The homeostatic drive to sleep (process S) is proportional to the duration of sleep restriction and becomes maximal at about 40 hours.
• Circadian regulation (process C) creates a drive for wakefulness that variably opposes process S and depends upon intrinsic rhythms.¹⁴

Neurons of the suprachiasmatic nucleus in the hypothalamus exert master coordination of this sleep/wake rhythm, along with other behavioral and physiologic variables.¹⁵ Because the typical intrinsic period is slightly longer than 24 hours, synchronization to the 24-hour day (entrainment) is accomplished by environmental inputs (zeitgebers, or “time givers”), the most important of which is exposure to light.¹⁶

Misalignment between endogenous circadian rhythms and the light/dark cycle can result in circadian rhythm sleep disorders, such as:

• delayed sleep timing (DSPD)
• advanced sleep timing (advanced sleep phase disorder)
• erratic sleep timing (irregular sleep/wake rhythm)
• complete dissociation from the light/dark cycle (circadian rhythm sleep disorder, free-running type).

These 4 conditions are thought to involve predominantly intrinsic mechanisms, but circadian dysrhythmias also can be induced by exogenous factors. Extreme work schedules or rapid travel across time zones can challenge the circadian system’s ability to acclimate and the individual’s ability to achieve a desired sleep schedule.¹⁷

Differential diagnosis

Because DSPD relates primarily to an aberration in timing of sleep, it is characterized as a disorder only if the individual’s preferred schedule interferes substantially with social or occupational functioning. The International Classification of Sleep Disorders (ICSD) provides detailed diagnostic criteria (Table).¹⁷

Table

Diagnostic criteria for delayed sleep phase disorder

Depression and anxiety often manifest with sleep difficulties, as do inadequate sleep hygiene and other conditions associated with prolonged sleep initiation. According to ICSD criteria, primary insomnia can be differentiated from DSPD if the patient readily initiates and maintains sleep when allowed to sleep on his/her desired sleep/wake schedule. Accumulated evidence has largely debunked this notion, however, as polysomnographic studies have demonstrated both prolonged sleep latency and impaired sleep efficiency in DSPD patients versus matched controls.³

Assessment tools can complement the clinical history in diagnosing DSPD. Either a sleep log or actigraphy is required to demonstrate a stable phase delay, but actigraphy typically generates more reliable data.¹⁸ Actigraphs are compact “motion detectors” whose output while being worn by patients allows longitudinal assessment of sleep/wake parameters.

Eveningness tendencies of presumptive DSPD patients can be further verified with the Morningness-Eveningness Questionnaire (MEQ) (Box 2).¹⁹ Low scores are associated with evening types—felt to correspond to the endogenous circadian period—and can help narrow the differential diagnosis of sleep-initiation complaints.²⁰

Box 2

CASE CONTINUED: ‘Definite evening type’

Jason scores 28 on the MEQ, consistent with a “definite evening type.” Actigraphic monitoring is scheduled during a school holiday, when he is instructed to sleep according to his preferred schedule with the least possible restriction.

A clearly delayed sleep phase is evident, with the habitual sleep period occurring between 5 AM and 1 PM. Even on days when he was quite sleep-restricted because of an enforced wake time, sleep onset on the ensuing evening was substantially delayed, suggesting an obligate nature for the delayed sleep/wake schedule. Overall, Jason had few complaints with respect to impaired alertness while on this unrestricted schedule and experienced a much more stable mood.

Interventions

Without physiologic assessments, understanding the patient’s “natural” sleep schedule can allow for rational recommendations about using phototherapy and oral melatonin (Figure²¹). However, referral to a sleep specialist is required unless the general psychiatrist has experience in treating circadian rhythm sleep disorders.

Morning phototherapy. Properly timed morning bright light therapy (≥2,500 lux) has been shown to help DSPD patients achieve physiologically measured sleep phase advances, objective improvements in daytime alertness, and earlier reported bedtimes compared with controls.²² Unfortunately, the described 2-hour treatment duration make this research protocol clinically impractical, and most clinicians commence with a 30-minute duration of therapy, as described in the seasonal affective disorder literature.

Relatively new and widely available blue light boxes have been reported to exhibit at least equivalent efficacy to bright light devices (as reported in the literature pertaining to seasonal affective disorder), but with markedly decreased light intensity and fewer associated adverse effects.²³ As the research addressing their use in the treatment of circadian rhythm sleep disorders is still emerging, their future role remains uncertain.

Precautions. Most psychiatrists would not perform a physiologic determination of a patient’s circadian phase, and further undesired phase delays can occur if phototherapy is administered before the core body temperature minimum (Tmin).²⁴ Also, use caution if prescribing phototherapy to patients taking photosensitizing drugs and/or those with ocular or retinal pathology.²⁰

Evening light avoidance. Whether or not you prescribe morning phototherapy, recommending that DSPD patients avoid evening light is essential to avoid further induction or exacerbation of phase delays. Protective eyewear is warranted in instances where these advisory precautions are insufficient (see Related Resources). Such an intervention has been shown effective in decreasing light exposure and undesired phase advances in studies involving subjects exposed to simulated shift work.²⁵

Oral melatonin. Abundant evidence supports melatonin use in achieving phase advances in individuals with DSPD.^26,27 A synergistic effect can be obtained when melatonin is combined with phototherapy.²⁸

Proper timing of melatonin to achieve a maximal phase advance can be estimated based on the individual’s dim light melatonin onset (DLMO), which occurs approximately 14 hours after the habitual (unrestricted) wake time.²⁹ Maximal phase advances appear to occur when melatonin is given approximately 6 hours before the DLMO.²⁶ Thus, a rational practice is to recommend that patients take melatonin 8 hours after their natural wake time. Doses of ≤0.5 mg appear to achieve the maximal chronobiotic effect while avoiding an undesired hypnotic effect.³⁰

Precautions. Verifying the purity of over-the-counter melatonin is difficult. A review by the National Academy of Sciences states that short-term use of melatonin, ≤10 mg/d, appears to be safe in healthy adults but recommends caution in children/adolescents and women of reproductive age. Doses recommended for circadian-based interventions are typically physiologic in nature (i.e., ≤0.5 mg), which may serve to mitigate these concerns.

Adverse effects such as headaches, somnolence, hypotension, hypertension, gastrointestinal upset, and exacerbation of alopecia areata have been reported at higher melatonin doses in healthy adults and at lower doses in persons with preexisting central nervous system, cardiovascular, gastrointestinal, or dermatologic conditions.³¹

Figure Light and melatonin phase response curves: Normal vs. delayed

This schematic compares ‘normal sleep’ phase response curves (PRCs) to light and exogenous melatonin with postulated PRCs for an individual with delayed sleep phase disorder (DSPD), presumed to be 5 hours ‘out of phase.’ Y-axis shows the direction and relative magnitude of phase shifts produced by light or melatonin at times shown on the x-axis. X-axis covers >24 hours to better illustrate the PRCs.
Relationships between ‘normal sleepers’ and DSPD patients are depicted by:

• rectangles (sleep period)
• triangles (core body temperature minimum [Tmin])
• arrows (dim light melatonin onsets [DLMOs]).

‘Normal’ sleep is shown to occur from midnight to 8 AM, and the DSPD patient’s sleep from 5 AM to 1 PM; DLMO and Tmin are similarly delayed by 5 hours in the DSPD patient. This schematic assumes that phase relationships are maintained in DSPD patients, which is not a certainty.
Source: Adapted from reference 21

CASE CONTINUED: Under the bright lights

Jason starts phototherapy treatment during his winter break, administering bright light daily upon natural awakening using a 10,000 lux light box for at least 30 minutes. As instructed, he gradually advances the time of administration by approximately 30 minutes every other day, striving for a nocturnal sleep period of 11 PM to 7 AM. He also wears protective eyewear to reduce light exposure during evening hours to avoid further delays in sleep phase. To further promote a phase advance, he takes oral melatonin, 0.5 mg/d at approximately 8 PM, as determined by his self-report and results of actigraphic recording.

Other options

Hypnotics. Little evidence supports the use of hypnotics in DSPD,³² and patients may show resistance to these drugs.³³ Nevertheless, hypnotics can heighten confidence in the ability to initiate sleep in individuals with a concomitant conditioned insomnia.

With chronotherapy, patients are prescribed a sleep schedule that is delayed several hours incrementally until sleep is aligned to a target bedtime. The individual then is advised to rigorously maintain a regular sleep/wake schedule, repeating the process as necessary.

Although case reports have shown positive results with chronotherapy for DSPD,³⁴ no controlled trials have demonstrated its efficacy or safety. One study reported high relapse rates,³¹ and 1 patient with DSPD developed free-running circadian rhythms.³⁵ Clinical experience suggests chronotherapy is impractical for patients who must adhere to a fixed schedule.

Behavioral approaches

For an adolescent with DSPD, consider asking the school district to allow him or her a later school start-time. This alone often can substantially increase total sleep time and mitigate associated impairments.³⁶ In all instances pursue and address external contributors to DSPD, such as poor sleep hygiene (including excessive caffeine use) and substance misuse.

Emphasize regular wake times, as arising later on weekends can cause phase delays.³⁷ DSPD patients may have a concomitant conditioned insomnia that responds to evidence-based behavioral treatments.³⁸

Whatever intervention you choose, schedule a follow-up appointment in approximately 2 months to evaluate patients’ progress and compliance. Encourage them to contact you with questions or concerns in the interim. Review sleep logs or actigraphy during this visit, and adjust the timing and/or nature of interventions as needed. Adolescents can be particularly noncompliant with clinical interventions, and therapeutic goals cannot be reached without their full investment.

Because no guidelines exist on how long to treat DSPD, stop on a “trial-and-error” basis when symptoms are controlled, and resume if they recur. Another approach is to maintain a desired sleep/wake schedule with bedtime melatonin and encourage continued adherence to other measures.

CASE CONTINUED: Maintenance therapy

Jason returns to the clinic approximately 10 weeks later. After an obviously concerted effort to adhere to treatment, his progress is quite remarkable. He rarely falls asleep later than 11 PM, so he is obtaining 2.5 hours more sleep each night before arising for school at 6:30 AM. Sleepiness at school is rarely problematic, and his mood is more stable.

He nevertheless describes a persistent tendency to retire and arise later and asks to continue melatonin and phototherapy. Because no guidelines exist for long-term therapy of DSPD, he is advised to switch melatonin to bedtime dosing (with a presumed phase-neutral “maintenance” effect), and to continue phototherapy as prescribed.

Related resources

• Wyatt JK. Delayed sleep phase syndrome: pathophysiology and treatment options. Sleep. 2004;27(6):1195-1203.
• Crowley SJ, Acebo C, Carskadon MA. Sleep, circadian rhythms, and delayed sleep phase in adolescence. Sleep Med. 2007;8(6):602-612.
• National Sleep Foundation. Adolescent sleep needs and patterns: research report and resource guide. Washington, DC; 2000:1-30.
• Products designed to assist in the avoidance of light at improper times. www.lowbluelights.com.

Disclosure

Dr. Auger reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Comment on this article

Jason, age 16, has had difficulty with sleep initiation for 2 years. He describes going to bed at 10:30 PM on school nights but falling asleep no sooner than midnight and typically after 1:30 AM. He denies contributions from an “active mind” or environmental disturbances, and his bedroom contains no TV, computer, or other media devices. He does not sleep better with a change in environment. He denies pervasive low mood symptoms and believes his mood hinges predominantly on his ability to achieve sufficient sleep.

Once asleep, Jason generally enjoys good sleep consolidation until he needs to arise at 6:30 AM. His mother awakens him with difficulty, as he often sleeps through his alarm. He sleeps approximately 5 hours nightly during the school week, endorses impaired concentration, and often dozes during his first several classes. When he returns home from school, he finds it very difficult to resist napping.

On weekends he retires at 1 AM or later and typically falls asleep within 30 minutes. He usually awakens at noon but can sleep as late as 4:30 PM. He feels slightly more refreshed on weekends and describes his mood then as improved. During a recent spring break, he felt much better when allowed to sleep as much as he wanted.

Delayed sleep phase disorder (DSPD)—characterized by a pathological “night owl” circadian preference—is seen most commonly in adolescents and is associated with psychiatric morbidity, psychosocial impairment, and poor academic performance. Proper identification of the condition can be enhanced with a variety of assessment tools, and successful treatment requires an awareness of potential endogenous and exogenous contributors.

This article describes what is known about DSPD and uses the case example to illustrate diagnostic assessment and treatment choices. Intriguing data support various pathophysiologic explanations for DSPD (Box 1).^1-6 Facilitating the adjustment of patients’ physiologic clocks is the overall goal in managing DSPD.

Box 1

Extreme ‘eveningness’

Because of their extreme seemingly innate preference to retire and arise at relatively late clock hours (an “eveningness” trait), school-aged patients with DSPD represent a high-risk population for problematic sleepiness. In a survey of 612 high school students, the 63% who felt they needed more sleep on school nights showed a strong eveningness preference (as assessed by questionnaire), compared with students who described getting sufficient sleep.⁷ Other studies have revealed psychiatric morbidity (including affective and personality disorders), psychosocial impairment, and poor academic performance associated with the condition.^8-10

DSPD may affect 7% to 16% of patients presenting with insomnia complaints in sleep medicine clinics.¹¹ The condition appears most common among young cohorts and has been reported to affect up to 7% of adolescents in the United States.¹² Its high frequency in this age group may be a pathologic exaggeration of the normal tendency toward delayed timing of sleep and wakefulness linked with pubertal development.¹³

Sleep and wakefulness regulation

Conceptually, 2 processes govern sleep and wakefulness:

• The homeostatic drive to sleep (process S) is proportional to the duration of sleep restriction and becomes maximal at about 40 hours.
• Circadian regulation (process C) creates a drive for wakefulness that variably opposes process S and depends upon intrinsic rhythms.¹⁴

Neurons of the suprachiasmatic nucleus in the hypothalamus exert master coordination of this sleep/wake rhythm, along with other behavioral and physiologic variables.¹⁵ Because the typical intrinsic period is slightly longer than 24 hours, synchronization to the 24-hour day (entrainment) is accomplished by environmental inputs (zeitgebers, or “time givers”), the most important of which is exposure to light.¹⁶

Misalignment between endogenous circadian rhythms and the light/dark cycle can result in circadian rhythm sleep disorders, such as:

• delayed sleep timing (DSPD)
• advanced sleep timing (advanced sleep phase disorder)
• erratic sleep timing (irregular sleep/wake rhythm)
• complete dissociation from the light/dark cycle (circadian rhythm sleep disorder, free-running type).

These 4 conditions are thought to involve predominantly intrinsic mechanisms, but circadian dysrhythmias also can be induced by exogenous factors. Extreme work schedules or rapid travel across time zones can challenge the circadian system’s ability to acclimate and the individual’s ability to achieve a desired sleep schedule.¹⁷

Differential diagnosis

Because DSPD relates primarily to an aberration in timing of sleep, it is characterized as a disorder only if the individual’s preferred schedule interferes substantially with social or occupational functioning. The International Classification of Sleep Disorders (ICSD) provides detailed diagnostic criteria (Table).¹⁷

Table

Diagnostic criteria for delayed sleep phase disorder

Depression and anxiety often manifest with sleep difficulties, as do inadequate sleep hygiene and other conditions associated with prolonged sleep initiation. According to ICSD criteria, primary insomnia can be differentiated from DSPD if the patient readily initiates and maintains sleep when allowed to sleep on his/her desired sleep/wake schedule. Accumulated evidence has largely debunked this notion, however, as polysomnographic studies have demonstrated both prolonged sleep latency and impaired sleep efficiency in DSPD patients versus matched controls.³

Assessment tools can complement the clinical history in diagnosing DSPD. Either a sleep log or actigraphy is required to demonstrate a stable phase delay, but actigraphy typically generates more reliable data.¹⁸ Actigraphs are compact “motion detectors” whose output while being worn by patients allows longitudinal assessment of sleep/wake parameters.

Eveningness tendencies of presumptive DSPD patients can be further verified with the Morningness-Eveningness Questionnaire (MEQ) (Box 2).¹⁹ Low scores are associated with evening types—felt to correspond to the endogenous circadian period—and can help narrow the differential diagnosis of sleep-initiation complaints.²⁰

Box 2

CASE CONTINUED: ‘Definite evening type’

Jason scores 28 on the MEQ, consistent with a “definite evening type.” Actigraphic monitoring is scheduled during a school holiday, when he is instructed to sleep according to his preferred schedule with the least possible restriction.

A clearly delayed sleep phase is evident, with the habitual sleep period occurring between 5 AM and 1 PM. Even on days when he was quite sleep-restricted because of an enforced wake time, sleep onset on the ensuing evening was substantially delayed, suggesting an obligate nature for the delayed sleep/wake schedule. Overall, Jason had few complaints with respect to impaired alertness while on this unrestricted schedule and experienced a much more stable mood.

Interventions

Without physiologic assessments, understanding the patient’s “natural” sleep schedule can allow for rational recommendations about using phototherapy and oral melatonin (Figure²¹). However, referral to a sleep specialist is required unless the general psychiatrist has experience in treating circadian rhythm sleep disorders.

Morning phototherapy. Properly timed morning bright light therapy (≥2,500 lux) has been shown to help DSPD patients achieve physiologically measured sleep phase advances, objective improvements in daytime alertness, and earlier reported bedtimes compared with controls.²² Unfortunately, the described 2-hour treatment duration make this research protocol clinically impractical, and most clinicians commence with a 30-minute duration of therapy, as described in the seasonal affective disorder literature.

Relatively new and widely available blue light boxes have been reported to exhibit at least equivalent efficacy to bright light devices (as reported in the literature pertaining to seasonal affective disorder), but with markedly decreased light intensity and fewer associated adverse effects.²³ As the research addressing their use in the treatment of circadian rhythm sleep disorders is still emerging, their future role remains uncertain.

Precautions. Most psychiatrists would not perform a physiologic determination of a patient’s circadian phase, and further undesired phase delays can occur if phototherapy is administered before the core body temperature minimum (Tmin).²⁴ Also, use caution if prescribing phototherapy to patients taking photosensitizing drugs and/or those with ocular or retinal pathology.²⁰

Evening light avoidance. Whether or not you prescribe morning phototherapy, recommending that DSPD patients avoid evening light is essential to avoid further induction or exacerbation of phase delays. Protective eyewear is warranted in instances where these advisory precautions are insufficient (see Related Resources). Such an intervention has been shown effective in decreasing light exposure and undesired phase advances in studies involving subjects exposed to simulated shift work.²⁵

Oral melatonin. Abundant evidence supports melatonin use in achieving phase advances in individuals with DSPD.^26,27 A synergistic effect can be obtained when melatonin is combined with phototherapy.²⁸

Proper timing of melatonin to achieve a maximal phase advance can be estimated based on the individual’s dim light melatonin onset (DLMO), which occurs approximately 14 hours after the habitual (unrestricted) wake time.²⁹ Maximal phase advances appear to occur when melatonin is given approximately 6 hours before the DLMO.²⁶ Thus, a rational practice is to recommend that patients take melatonin 8 hours after their natural wake time. Doses of ≤0.5 mg appear to achieve the maximal chronobiotic effect while avoiding an undesired hypnotic effect.³⁰

Precautions. Verifying the purity of over-the-counter melatonin is difficult. A review by the National Academy of Sciences states that short-term use of melatonin, ≤10 mg/d, appears to be safe in healthy adults but recommends caution in children/adolescents and women of reproductive age. Doses recommended for circadian-based interventions are typically physiologic in nature (i.e., ≤0.5 mg), which may serve to mitigate these concerns.

Adverse effects such as headaches, somnolence, hypotension, hypertension, gastrointestinal upset, and exacerbation of alopecia areata have been reported at higher melatonin doses in healthy adults and at lower doses in persons with preexisting central nervous system, cardiovascular, gastrointestinal, or dermatologic conditions.³¹

Figure Light and melatonin phase response curves: Normal vs. delayed

This schematic compares ‘normal sleep’ phase response curves (PRCs) to light and exogenous melatonin with postulated PRCs for an individual with delayed sleep phase disorder (DSPD), presumed to be 5 hours ‘out of phase.’ Y-axis shows the direction and relative magnitude of phase shifts produced by light or melatonin at times shown on the x-axis. X-axis covers >24 hours to better illustrate the PRCs.
Relationships between ‘normal sleepers’ and DSPD patients are depicted by:

• rectangles (sleep period)
• triangles (core body temperature minimum [Tmin])
• arrows (dim light melatonin onsets [DLMOs]).

‘Normal’ sleep is shown to occur from midnight to 8 AM, and the DSPD patient’s sleep from 5 AM to 1 PM; DLMO and Tmin are similarly delayed by 5 hours in the DSPD patient. This schematic assumes that phase relationships are maintained in DSPD patients, which is not a certainty.
Source: Adapted from reference 21

CASE CONTINUED: Under the bright lights

Jason starts phototherapy treatment during his winter break, administering bright light daily upon natural awakening using a 10,000 lux light box for at least 30 minutes. As instructed, he gradually advances the time of administration by approximately 30 minutes every other day, striving for a nocturnal sleep period of 11 PM to 7 AM. He also wears protective eyewear to reduce light exposure during evening hours to avoid further delays in sleep phase. To further promote a phase advance, he takes oral melatonin, 0.5 mg/d at approximately 8 PM, as determined by his self-report and results of actigraphic recording.

Other options

Hypnotics. Little evidence supports the use of hypnotics in DSPD,³² and patients may show resistance to these drugs.³³ Nevertheless, hypnotics can heighten confidence in the ability to initiate sleep in individuals with a concomitant conditioned insomnia.

With chronotherapy, patients are prescribed a sleep schedule that is delayed several hours incrementally until sleep is aligned to a target bedtime. The individual then is advised to rigorously maintain a regular sleep/wake schedule, repeating the process as necessary.

Although case reports have shown positive results with chronotherapy for DSPD,³⁴ no controlled trials have demonstrated its efficacy or safety. One study reported high relapse rates,³¹ and 1 patient with DSPD developed free-running circadian rhythms.³⁵ Clinical experience suggests chronotherapy is impractical for patients who must adhere to a fixed schedule.

Behavioral approaches

For an adolescent with DSPD, consider asking the school district to allow him or her a later school start-time. This alone often can substantially increase total sleep time and mitigate associated impairments.³⁶ In all instances pursue and address external contributors to DSPD, such as poor sleep hygiene (including excessive caffeine use) and substance misuse.

Emphasize regular wake times, as arising later on weekends can cause phase delays.³⁷ DSPD patients may have a concomitant conditioned insomnia that responds to evidence-based behavioral treatments.³⁸

Whatever intervention you choose, schedule a follow-up appointment in approximately 2 months to evaluate patients’ progress and compliance. Encourage them to contact you with questions or concerns in the interim. Review sleep logs or actigraphy during this visit, and adjust the timing and/or nature of interventions as needed. Adolescents can be particularly noncompliant with clinical interventions, and therapeutic goals cannot be reached without their full investment.

Because no guidelines exist on how long to treat DSPD, stop on a “trial-and-error” basis when symptoms are controlled, and resume if they recur. Another approach is to maintain a desired sleep/wake schedule with bedtime melatonin and encourage continued adherence to other measures.

CASE CONTINUED: Maintenance therapy

Jason returns to the clinic approximately 10 weeks later. After an obviously concerted effort to adhere to treatment, his progress is quite remarkable. He rarely falls asleep later than 11 PM, so he is obtaining 2.5 hours more sleep each night before arising for school at 6:30 AM. Sleepiness at school is rarely problematic, and his mood is more stable.

He nevertheless describes a persistent tendency to retire and arise later and asks to continue melatonin and phototherapy. Because no guidelines exist for long-term therapy of DSPD, he is advised to switch melatonin to bedtime dosing (with a presumed phase-neutral “maintenance” effect), and to continue phototherapy as prescribed.

Related resources

• Wyatt JK. Delayed sleep phase syndrome: pathophysiology and treatment options. Sleep. 2004;27(6):1195-1203.
• Crowley SJ, Acebo C, Carskadon MA. Sleep, circadian rhythms, and delayed sleep phase in adolescence. Sleep Med. 2007;8(6):602-612.
• National Sleep Foundation. Adolescent sleep needs and patterns: research report and resource guide. Washington, DC; 2000:1-30.
• Products designed to assist in the avoidance of light at improper times. www.lowbluelights.com.

Disclosure

Dr. Auger reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

The economic stimulus bill that became law last week includes several items on SHM's healthcare policy wish list.

"It clearly hits some key issues," Eric Siegal, MD, chair of SHM's Public Policy Committee, says in regard to the American Recovery and Reinvestment Act. "This is a step in the right direction."

The $787 billion stimulus package includes:

• $1.1 billion for comparative effectiveness research (CER). Funding for CER is one of SHM's top policy priorities, says Laura Allendorf, SHM's senior advisor for advocacy and government affairs. CER examines the effectiveness of multiple therapies for specific medical conditions, or for a specific set of patients, to determine the best care options. "Funding for this is long overdue and key to healthcare reform," Dr. Siegal says. CER money will be split among the major players in this research, including the National Institutes of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ).
• A 34% increase in NIH funding. This includes $8.5 billion for research grants and programs that will allow for as many as 15,000 additional grants. "We know that an investment in biomedical research is an investment in the future of healthcare," says David Meltzer, MD, PhD, chair of SHM's Research Committee.
• $19 billion for health information technology. Incentives—and penalties—will target adoption of electronic health records by hospitals and office-based practices. "This will help improve patient safety, as well as care coordination," Allendorf says.

Other healthcare provisions in the package include an additional $86.6 billion in federal Medicaid funds, as well as temporary Medicaid coverage for the recently unemployed.

To keep up with public policy initiatives, check out SHM's advocacy portal.

The economic stimulus bill that became law last week includes several items on SHM's healthcare policy wish list.

"It clearly hits some key issues," Eric Siegal, MD, chair of SHM's Public Policy Committee, says in regard to the American Recovery and Reinvestment Act. "This is a step in the right direction."

The $787 billion stimulus package includes:

• $1.1 billion for comparative effectiveness research (CER). Funding for CER is one of SHM's top policy priorities, says Laura Allendorf, SHM's senior advisor for advocacy and government affairs. CER examines the effectiveness of multiple therapies for specific medical conditions, or for a specific set of patients, to determine the best care options. "Funding for this is long overdue and key to healthcare reform," Dr. Siegal says. CER money will be split among the major players in this research, including the National Institutes of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ).
• A 34% increase in NIH funding. This includes $8.5 billion for research grants and programs that will allow for as many as 15,000 additional grants. "We know that an investment in biomedical research is an investment in the future of healthcare," says David Meltzer, MD, PhD, chair of SHM's Research Committee.
• $19 billion for health information technology. Incentives—and penalties—will target adoption of electronic health records by hospitals and office-based practices. "This will help improve patient safety, as well as care coordination," Allendorf says.

Other healthcare provisions in the package include an additional $86.6 billion in federal Medicaid funds, as well as temporary Medicaid coverage for the recently unemployed.

To keep up with public policy initiatives, check out SHM's advocacy portal.

The economic stimulus bill that became law last week includes several items on SHM's healthcare policy wish list.

"It clearly hits some key issues," Eric Siegal, MD, chair of SHM's Public Policy Committee, says in regard to the American Recovery and Reinvestment Act. "This is a step in the right direction."

The $787 billion stimulus package includes:

• $1.1 billion for comparative effectiveness research (CER). Funding for CER is one of SHM's top policy priorities, says Laura Allendorf, SHM's senior advisor for advocacy and government affairs. CER examines the effectiveness of multiple therapies for specific medical conditions, or for a specific set of patients, to determine the best care options. "Funding for this is long overdue and key to healthcare reform," Dr. Siegal says. CER money will be split among the major players in this research, including the National Institutes of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ).
• A 34% increase in NIH funding. This includes $8.5 billion for research grants and programs that will allow for as many as 15,000 additional grants. "We know that an investment in biomedical research is an investment in the future of healthcare," says David Meltzer, MD, PhD, chair of SHM's Research Committee.
• $19 billion for health information technology. Incentives—and penalties—will target adoption of electronic health records by hospitals and office-based practices. "This will help improve patient safety, as well as care coordination," Allendorf says.

Other healthcare provisions in the package include an additional $86.6 billion in federal Medicaid funds, as well as temporary Medicaid coverage for the recently unemployed.

To keep up with public policy initiatives, check out SHM's advocacy portal.

The recent death of an up-and-coming Brazilian model due to sepsis has again drawn attention to the common disease and how hospitalists should be wary not to miss its diagnosis in hospitalized patients.

Mariana Bridi da Costa, a 20-year-old beauty queen who participated in international competitions, died Jan. 24 from septicemia that began with a urinary tract infection. The original diagnosis did not include the urinary tract infection, leading to severe sepsis. Septicemia kills about 1,400 people a day worldwide, according to the Society of Critical Care Medicine (SCCM). The sepsis mortality rate is on a similar scale to lung, breast, and colon cancer, SCCM data shows.

"When someone comes in with high fever, high heart rate, high respiratory rate, and low blood pressure, you have to begin thinking about how well their organs are working," says Jeffrey Dichter, MD, medical director of cardiovascular intensive care at Regions Hospital in St. Paul, Minn., and former HM program director. "How sick are they? ... Hospitalists should look for the source of infection and evidence of organ failure."

According to the Mayo Clinic, about 750,000 people in the U.S. contract severe sepsis each year, and more than 200,000 people die of it.

Dr. Dichter notes that hospitalists in any setting—from acute-care hospitals to off-site clinics—can run blood tests for kidney and liver functions, as well as electrolyte levels, that serve as quick windows into the presence of sepsis. He also promotes www.survivingsepsis.org, the SCCM's program that aims to reduce sepsis mortality by 25% in five years by defining the disease more clearly and improving its diagnosis.

"Sometimes the symptoms patients come in with seem subtle," Dr. Dichter says. "Sometimes they may come in with evidence of an infection or low blood pressure, but they're awake and alert and talking and seem very normal. … Hospitalists need to be attune."

The recent death of an up-and-coming Brazilian model due to sepsis has again drawn attention to the common disease and how hospitalists should be wary not to miss its diagnosis in hospitalized patients.

Mariana Bridi da Costa, a 20-year-old beauty queen who participated in international competitions, died Jan. 24 from septicemia that began with a urinary tract infection. The original diagnosis did not include the urinary tract infection, leading to severe sepsis. Septicemia kills about 1,400 people a day worldwide, according to the Society of Critical Care Medicine (SCCM). The sepsis mortality rate is on a similar scale to lung, breast, and colon cancer, SCCM data shows.

"When someone comes in with high fever, high heart rate, high respiratory rate, and low blood pressure, you have to begin thinking about how well their organs are working," says Jeffrey Dichter, MD, medical director of cardiovascular intensive care at Regions Hospital in St. Paul, Minn., and former HM program director. "How sick are they? ... Hospitalists should look for the source of infection and evidence of organ failure."

According to the Mayo Clinic, about 750,000 people in the U.S. contract severe sepsis each year, and more than 200,000 people die of it.

Dr. Dichter notes that hospitalists in any setting—from acute-care hospitals to off-site clinics—can run blood tests for kidney and liver functions, as well as electrolyte levels, that serve as quick windows into the presence of sepsis. He also promotes www.survivingsepsis.org, the SCCM's program that aims to reduce sepsis mortality by 25% in five years by defining the disease more clearly and improving its diagnosis.

"Sometimes the symptoms patients come in with seem subtle," Dr. Dichter says. "Sometimes they may come in with evidence of an infection or low blood pressure, but they're awake and alert and talking and seem very normal. … Hospitalists need to be attune."

The recent death of an up-and-coming Brazilian model due to sepsis has again drawn attention to the common disease and how hospitalists should be wary not to miss its diagnosis in hospitalized patients.

Mariana Bridi da Costa, a 20-year-old beauty queen who participated in international competitions, died Jan. 24 from septicemia that began with a urinary tract infection. The original diagnosis did not include the urinary tract infection, leading to severe sepsis. Septicemia kills about 1,400 people a day worldwide, according to the Society of Critical Care Medicine (SCCM). The sepsis mortality rate is on a similar scale to lung, breast, and colon cancer, SCCM data shows.

"When someone comes in with high fever, high heart rate, high respiratory rate, and low blood pressure, you have to begin thinking about how well their organs are working," says Jeffrey Dichter, MD, medical director of cardiovascular intensive care at Regions Hospital in St. Paul, Minn., and former HM program director. "How sick are they? ... Hospitalists should look for the source of infection and evidence of organ failure."

According to the Mayo Clinic, about 750,000 people in the U.S. contract severe sepsis each year, and more than 200,000 people die of it.

Dr. Dichter notes that hospitalists in any setting—from acute-care hospitals to off-site clinics—can run blood tests for kidney and liver functions, as well as electrolyte levels, that serve as quick windows into the presence of sepsis. He also promotes www.survivingsepsis.org, the SCCM's program that aims to reduce sepsis mortality by 25% in five years by defining the disease more clearly and improving its diagnosis.

"Sometimes the symptoms patients come in with seem subtle," Dr. Dichter says. "Sometimes they may come in with evidence of an infection or low blood pressure, but they're awake and alert and talking and seem very normal. … Hospitalists need to be attune."

Question: Do blood transfusions in hospitalized cancer patients with anemia or thrombocytopenia affect thrombotic event and in-hospital mortality rates?

Background: Erythropoiesis-stimulating agents have recently been shown to increase thrombotic risk and decrease survival in cancer patients. Blood transfusions are a common alternative for anemic patients. However, there are no randomized trials demonstrating improved outcomes in cancer patients receiving transfusions. Furthermore, the safety of transfusions has not been clearly defined.

Study design: Retrospective, cohort study.

Setting: 60 U.S. medical centers.

Synopsis: Using discharge data from the University Health System Consortium, 504,208 hospitalizations of cancer patients revealed that 14% of patients received at least one RBC transfusion and 3% of patients received a platelet transfusion. RBC and platelet transfusions were associated with increased risk of arterial thrombosis (RBCs: OR 1.53; 95% CI 1.46-1.61; platelets: OR 1.55; 1.4-1.71, P<0.001) and venous thrombotic events (RBCs: OR 1.34; 1.29-1.38; platelets: OR 1.2; 1.11-1.29, P<0.001). Additionally, transfusions were associated with increased in-hospital mortality (RBCs: OR 1.34; 1.29-1.38; platelets: OR 2.4; 2.27-2.52, P<0.001). Study results are limited by several factors, including the observational nature and the use of administrative coding data. Information on venous thromboembolism prophylaxis was not available, and the timing of transfusions in relation to the diagnosis of thrombotic events is unknown. Finally, anemia-necessitating transfusions may be a surrogate for "sicker" patients, explaining the increased in-hospital mortality. Blood transfusions in hospitalized patients require further study to determine whether there is a causal relationship between transfusions and increased thrombotic events and mortality.

Bottom line: Blood transfusions in hospitalized cancer patients should be used cautiously, as they are associated with increased thrombotic events and in-hospital mortality.

Citation: Arch Int Med. 2008;168:2377-2381

—Reviewed for the eWire by Kerry Will, MD, Jayne Barr, MD, Kim Tartaglia, MD, Aaron Wenger, MD, Jonathan Wynbrandt, MD, Nathan J. O’Dorisio, MD, The Ohio State University Medical Center, Columbus, OH.

Question: Do blood transfusions in hospitalized cancer patients with anemia or thrombocytopenia affect thrombotic event and in-hospital mortality rates?

Background: Erythropoiesis-stimulating agents have recently been shown to increase thrombotic risk and decrease survival in cancer patients. Blood transfusions are a common alternative for anemic patients. However, there are no randomized trials demonstrating improved outcomes in cancer patients receiving transfusions. Furthermore, the safety of transfusions has not been clearly defined.

Study design: Retrospective, cohort study.

Setting: 60 U.S. medical centers.

Synopsis: Using discharge data from the University Health System Consortium, 504,208 hospitalizations of cancer patients revealed that 14% of patients received at least one RBC transfusion and 3% of patients received a platelet transfusion. RBC and platelet transfusions were associated with increased risk of arterial thrombosis (RBCs: OR 1.53; 95% CI 1.46-1.61; platelets: OR 1.55; 1.4-1.71, P<0.001) and venous thrombotic events (RBCs: OR 1.34; 1.29-1.38; platelets: OR 1.2; 1.11-1.29, P<0.001). Additionally, transfusions were associated with increased in-hospital mortality (RBCs: OR 1.34; 1.29-1.38; platelets: OR 2.4; 2.27-2.52, P<0.001). Study results are limited by several factors, including the observational nature and the use of administrative coding data. Information on venous thromboembolism prophylaxis was not available, and the timing of transfusions in relation to the diagnosis of thrombotic events is unknown. Finally, anemia-necessitating transfusions may be a surrogate for "sicker" patients, explaining the increased in-hospital mortality. Blood transfusions in hospitalized patients require further study to determine whether there is a causal relationship between transfusions and increased thrombotic events and mortality.

Bottom line: Blood transfusions in hospitalized cancer patients should be used cautiously, as they are associated with increased thrombotic events and in-hospital mortality.

Citation: Arch Int Med. 2008;168:2377-2381

—Reviewed for the eWire by Kerry Will, MD, Jayne Barr, MD, Kim Tartaglia, MD, Aaron Wenger, MD, Jonathan Wynbrandt, MD, Nathan J. O’Dorisio, MD, The Ohio State University Medical Center, Columbus, OH.

Question: Do blood transfusions in hospitalized cancer patients with anemia or thrombocytopenia affect thrombotic event and in-hospital mortality rates?

Background: Erythropoiesis-stimulating agents have recently been shown to increase thrombotic risk and decrease survival in cancer patients. Blood transfusions are a common alternative for anemic patients. However, there are no randomized trials demonstrating improved outcomes in cancer patients receiving transfusions. Furthermore, the safety of transfusions has not been clearly defined.

Study design: Retrospective, cohort study.

Setting: 60 U.S. medical centers.

Synopsis: Using discharge data from the University Health System Consortium, 504,208 hospitalizations of cancer patients revealed that 14% of patients received at least one RBC transfusion and 3% of patients received a platelet transfusion. RBC and platelet transfusions were associated with increased risk of arterial thrombosis (RBCs: OR 1.53; 95% CI 1.46-1.61; platelets: OR 1.55; 1.4-1.71, P<0.001) and venous thrombotic events (RBCs: OR 1.34; 1.29-1.38; platelets: OR 1.2; 1.11-1.29, P<0.001). Additionally, transfusions were associated with increased in-hospital mortality (RBCs: OR 1.34; 1.29-1.38; platelets: OR 2.4; 2.27-2.52, P<0.001). Study results are limited by several factors, including the observational nature and the use of administrative coding data. Information on venous thromboembolism prophylaxis was not available, and the timing of transfusions in relation to the diagnosis of thrombotic events is unknown. Finally, anemia-necessitating transfusions may be a surrogate for "sicker" patients, explaining the increased in-hospital mortality. Blood transfusions in hospitalized patients require further study to determine whether there is a causal relationship between transfusions and increased thrombotic events and mortality.

Bottom line: Blood transfusions in hospitalized cancer patients should be used cautiously, as they are associated with increased thrombotic events and in-hospital mortality.

Citation: Arch Int Med. 2008;168:2377-2381

—Reviewed for the eWire by Kerry Will, MD, Jayne Barr, MD, Kim Tartaglia, MD, Aaron Wenger, MD, Jonathan Wynbrandt, MD, Nathan J. O’Dorisio, MD, The Ohio State University Medical Center, Columbus, OH.

A multidisciplinary pre-discharge intervention—one that hospitalists can advocate for and help lead—resulted in a 30% reduction in hospital utilization within 30 days, according to a single-center study published in the Feb. 3 Annals of Internal Medicine (2009;150(3):178-187).

Researchers, including hospitalist Jeffrey Greenwald, MD, followed 749 adult patients over 30-day periods at Boston Medical Center to test the effects of a nurse discharge advocate program. A nurse arranged follow-up appointments and confirmed medication, while a clinical pharmacist called patients two to four days after discharge to reinforce the discharge plan.

"It isn't realistic that the hospitalists become the primary-care doctors after the discharge," says Dr. Greenwald, director of HM at Boston Medical Center and associate professor of medicine at Boston University School of Medicine. "It's critical that the hospitalists take a lead role in taking responsibility for the pitfalls into which the patients are likely to fall."

Dr. Greenwald thinks hospitalists can push for interventions at their respective centers to reduce rehospitalizations. The research team already is working on a new study to determine which measures could be automated to ensure their completion.

"All we're asking is that, as a team, you put in place the common stopgaps. ... None of this is gene therapy," Dr. Greenwald says. "This is low brain activity. The problem is that it's not low resource intense, and it's not low culture change."

Dr. Greenwald plans to submit information about his study to SHM's Project BOOST (Better Outcomes for Older Adults through Safe Transitions), a mentoring program meant to help hospitalists redesign their discharge process to improve patient outcomes. He says programs like Project BOOST are helping to draw attention to post-discharge protocols at hospitals around the country.

A multidisciplinary pre-discharge intervention—one that hospitalists can advocate for and help lead—resulted in a 30% reduction in hospital utilization within 30 days, according to a single-center study published in the Feb. 3 Annals of Internal Medicine (2009;150(3):178-187).

Researchers, including hospitalist Jeffrey Greenwald, MD, followed 749 adult patients over 30-day periods at Boston Medical Center to test the effects of a nurse discharge advocate program. A nurse arranged follow-up appointments and confirmed medication, while a clinical pharmacist called patients two to four days after discharge to reinforce the discharge plan.

"It isn't realistic that the hospitalists become the primary-care doctors after the discharge," says Dr. Greenwald, director of HM at Boston Medical Center and associate professor of medicine at Boston University School of Medicine. "It's critical that the hospitalists take a lead role in taking responsibility for the pitfalls into which the patients are likely to fall."

Dr. Greenwald thinks hospitalists can push for interventions at their respective centers to reduce rehospitalizations. The research team already is working on a new study to determine which measures could be automated to ensure their completion.

"All we're asking is that, as a team, you put in place the common stopgaps. ... None of this is gene therapy," Dr. Greenwald says. "This is low brain activity. The problem is that it's not low resource intense, and it's not low culture change."

Dr. Greenwald plans to submit information about his study to SHM's Project BOOST (Better Outcomes for Older Adults through Safe Transitions), a mentoring program meant to help hospitalists redesign their discharge process to improve patient outcomes. He says programs like Project BOOST are helping to draw attention to post-discharge protocols at hospitals around the country.

A multidisciplinary pre-discharge intervention—one that hospitalists can advocate for and help lead—resulted in a 30% reduction in hospital utilization within 30 days, according to a single-center study published in the Feb. 3 Annals of Internal Medicine (2009;150(3):178-187).

Researchers, including hospitalist Jeffrey Greenwald, MD, followed 749 adult patients over 30-day periods at Boston Medical Center to test the effects of a nurse discharge advocate program. A nurse arranged follow-up appointments and confirmed medication, while a clinical pharmacist called patients two to four days after discharge to reinforce the discharge plan.

"It isn't realistic that the hospitalists become the primary-care doctors after the discharge," says Dr. Greenwald, director of HM at Boston Medical Center and associate professor of medicine at Boston University School of Medicine. "It's critical that the hospitalists take a lead role in taking responsibility for the pitfalls into which the patients are likely to fall."

Dr. Greenwald thinks hospitalists can push for interventions at their respective centers to reduce rehospitalizations. The research team already is working on a new study to determine which measures could be automated to ensure their completion.

"All we're asking is that, as a team, you put in place the common stopgaps. ... None of this is gene therapy," Dr. Greenwald says. "This is low brain activity. The problem is that it's not low resource intense, and it's not low culture change."

Dr. Greenwald plans to submit information about his study to SHM's Project BOOST (Better Outcomes for Older Adults through Safe Transitions), a mentoring program meant to help hospitalists redesign their discharge process to improve patient outcomes. He says programs like Project BOOST are helping to draw attention to post-discharge protocols at hospitals around the country.