domingo, 30 de octubre de 2011

Clinical Case Nº5

A 24 years-old man arrives to emergency department complaining dyspnea, fever, coughing blood, astenia, pleuritic pain on the left chest. A Chest X-ray is taken inmediately (image). The leucocyte counting revealed 21.300 cells, with neutrophilia. PaO2  69 mmhg. After 3 days of continues antibiotic treatment with: oral cephalosporins, azytromicin and levofloxacine, the patient stills with the same symptoms. A Broncoscopy is performed without any results.



¿What is the Diagnose?

INTRALOBAR PULMONARY SEQUESTRATION

Intralobar pulmonary sequestration is an uncommon but distinct  
clinical  entity that  may  be  the  unrecognized
cause of  recurrent pulmonary infections. The term seques-
tration,  derived  from the Latin verb sequestrure,  “to sepa-
rate,”  was  coined  by  Pryce  in  1946  [l] after his  clear
description  established intralobar  sequestration as a  dis-
tinct  clinical  entity.  Generally  regarded  to result from
disturbed  embryogenesis,  a sequestration is encountered
in 1% to 2% of  all pulmonary  resections  [2]. This malfor-
mation  is  characterized by cystic  nonfunctioning  lung
tissue that usually has no communication with the normal
bronchial tree and that receives its blood supply from an
anomalous  systemic artery. The sequestration consists of
normal  lung  elements  in  an  abnormal  and  disorderly
arrangement  with  variable cartilage, bronchial glands,
a n d  alveolar parenchyma. One or more mucus-filled cysts
result  from  mucous  secretion  into  dilated, obstructed
bronchioles  and alveoli,  causing compression aletectasis
of  surrounding parenchyma  (Fig 1). Microscopic commu-
nications with adjacent normal lung allow air and, some-
times, bacteria to enter the cysts.  If  infection is superim-
posed,  the  cysts  may  contain  purulent  material.  In  the
usual case there is extensive acute and chronic organizing
inflammation, usually  so severe that  little normal tissue
remains. Occasionally there is only a single large cyst or a
noncystic mass containing branching bronchi that  run in
the  direction  of  the aberrent  artery. Apparently  it  takes
years for these changes to occur, because the disease only
rarely becomes apparent in early infancy.
Two types  of  pulmonary sequestration exist: an intra-
lobar sequestration, in which the abnormal tissue is partly
surrounded  by  normal  lung  and  contained within  the
visceral pleura, and less commonly, an extralobar type, in
which  the  abnormal  lung  tissue  has  its  own  distinct
pleural  investment  and  maintains complete anatomical
and  physiological  separation  from  the  adjacent normal
lung.
Several theories have  attempted  in the past to explain
the embryology of  pulmonary sequestration  [l, 31.  How-
ever, they  failed to  offer a common  pathogenesis  to the
multitude of  different clinical presentations. The presence
of  communications  between the  intestinal tract  and  se-
questrations led Gerle and associates [4] to the  develop-
ment  of  a  unified  theory  of  formation  of  intralobar  and
extralobar sequestrations. This theory,  supported  by the
pathohistological studies of  Iwai and co-workers [5], pro-
poses that an additional or accessory lung bud develops in
the early embryo from the ventral aspect of  the primitive
foregut distal to the site of  formation  of  the normal lung
bud.  The accessory lung  bud  migrates  caudad  with  the
normally developing  lung and  receives its blood  supply
from the embryonic splanchnic plexus, which has numer-
ous connections to the primitive dorsal aorta. The vascu-
lar  connections  to the  dorsal aorta persist  and  form the
anomalous arterial  supply  of  the  developing  pulmonary
sequestration.
The time at which the accessory lung bud  develops in
the embryo determines whether the resulting malforma-
tion will be intralobar or extralobar. The  fact that  only a
few sequestrations maintain a patent connection with the
esophagus  or stomach may be  explained by  inadequate mass. 
Special interest in this malformation first arose in
blood  supply to the communication resulting in its invo-
lution  [4]. Simultaneously occurring intralobar and extra-
lobar pulmonary sequestrations in which the lesions were
noted to be communicating with the gastrointestinal tract
strongly support the common origin theory [6]. Albrecht-
sen [7j reported  on  a patient with  an  extralobar pulmo-
nary sequestration connected  by  a  narrow  lung  tissue
pedicle  to  the  left  lower  lobe. This case  represents  a
definite intermediate link between intralobar and extralo-
bar sequestration,  suggesting these lesions are intimately
related in etiology and pathogenesis.  With regard to the
multitude of  anatomical variations, intralobar and extra-
lobar sequestrations represent part of  a spectrum of  mal-
formations, designated “bronchopulmonary-foregut  mal-
formations” by Gerle and associates [4]. At one end of  the
spectrum is a n  anomalous arterial supply to normal lung.
At the other end of  the spectrum is abnormal pulmonary
tissue  but without anomalous  arterial supply; namely,
bronchogenic cyst, lobar emphysema, and adenomatoid
malformation. Between these two extremes lie the  vari-
ants of  sequestration. Recently Rodgers and  co-workers
[8] have suggested that the term bronchopulmonary-foregut
malformation  is best reserved  for  those abnormalities of
ventral foregut budding directly involving the pulmonary
parenchyma and originating from either the tracheobron-
chial  tree  or the  gastrointestinal tract, such  as  bron-
chogenic cysts, sequestrations,  and tracheal lobes. They
did not include lobar emphysema and cystic adenomatoid
malformations, which involve local aberrations of  paren-
chymal development.
The  presenting  complaint in  the  majority  of  patients
harboring  a  sequestration  is  either repeated  localized
pulmonary  infections  or  an  asymptomatic intrathoracic
1940 when Harris and Lewis [9] reported operative injury
of  an anomalous artery to a lower lobe, resulting in the
child’s death. Although death due  to operative trauma to
an anomalous artery has subsequently been reported [2],
most  studies have  shown that  pulmonary sequestration
can  be  diagnosed accurately before operation  and  that
surgical resection can usually be carried out safely. This
paper summarizes our clinical experience with  the  diag-
nosis and  management  of  intralobar  sequestration, em-
phasizing the unfortunate delay in diagnosis often accom-
panying this malformation.

Charatecteristics and diferential Diagnose

The position of a lesion and its persistence in a relatively young individual raises the index of suspicion that the underlying pathology may be the result of a sequestered segment. Demonstration of a dominant feeding vessel, usually from the aorta or its major vessels, and venous drainage to the pulmonary veins suggests the diagnosis.
Alternative venous drainage patterns in ILS include a route directly into the left atrium via the azygos or hemiazygos systems, into intercostals veins, or into the inferior vena cava (IVC) or superior vena cava (SVC).
The finding of alternative venous drainage patterns separates pulmonary sequestration from other diagnoses, such as infection and tumor, round atelectasis, Bochdalek hernia, and pulmonary infarction. Enlargement of the associated abnormal feeding vessels is a constant feature, and the azygos vein is also frequently enlarged.
Multiple supply arteries are found in 15% of sequestrations; 73% of sequestrations develop blood vessels leading off the abdominal aorta, and 18% develop blood vessels leading off the thoracic aorta. Rare documented origins include the ascending aorta and the arch, subclavian, innominate, celiac, right coronary, and circumflex arteries.
Extralobar sequestration
In ELS, 80% of sequestrations lie between the lower lobe and the diaphragm. Lesions are usually located in the region of the posterior basal segments of the lower lobes. Left-sided lesions are more common than right-sided lesions. The mass may be closely associated with the esophagus, and fistulae may develop.
Subdiaphragmatic ELS lesions can mimic masses arising in various organs, such as the adrenal gland. In addition, ELS frequently is associated with other congenital extrapulmonary anomalies. Venous drainage occurs via the systemic circulation.
Many patients with ELS present in infancy with respiratory distress and chronic cough; some lesions are diagnosed coincidentally.
Intralobar sequestration
In ILS, sequestrations occur within pulmonary visceral pleurae and do not communicate with the bronchial tree. ILS is seen in males and females in equal numbers. The lesions of ILS may be solid, fluid, or hemorrhagic or may contain mucus. Cystic or emphysematous elements may be present, and adjacent atelectasis often exists.
Most lesions appear hypervascular, because of abundant systemic vascularization. Super-added infection may lead to some consolidation in adjacent segments, and a chronic inflammatory process may induce localized reactive neovascularization. Mucoid impaction of a bronchus surrounded by a hyperinflated lung is believed to be characteristic of ILS.
Intrapulmonary sequestration is usually diagnosed later than ELS, being found in childhood or adulthood when the patient presents with an infection

Radiography
Conventional chest radiographic findings vary depending on the size of the lesion and whether the lesion is infected. Other factors that cause abnormal radiographic findings are the presence or absence of communication with an airway or contiguous lung tissue and the presence of associated anomalies
An uninfected sequestration is seen as a well-defined mass or, less commonly, as a cyst in the medial aspect of a posterior lung base. An infected sequestration tends to appear ill defined, may be associated with a parapneumonic effusion, and may contain one or more fluid levels.
Occasionally in ELS, a small bump may be seen on the hemidiaphragm or the inferior paravertebral region.
Rarely, a large sequestration may present with an opaque hemithorax, with or without ipsilateral effusion.
With a barium/contrast swallow study, communication between the GI tract and a sequestrated lung segment has been described and may be demonstrated by means of a contrast-enhanced examination of the esophagus.
Mass effect is demonstrated on bronchography as displacement of terminal bronchi by the sequestration. Contrast-agent filling of the sequestered segment in intralobar lesions is uncommon, even when air-fluid levels are present within the cyst. In some patients, a blind intermediate portion of right bronchus may be seen because of hypoplasia of the middle and lower lobes in ELS. CT scans can demonstrate the lack of bronchi entering a sequestration


Angiography

The blood supply of 75% of pulmonary sequestrations is derived from the thoracic or abdominal aorta. The remaining 25% of sequestrations receive their blood flow from the subclavian, intercostal, pulmonary, pericardiophrenic, innominate, internal mammary, celiac, splenic, or renal arteries. The arterial supply typically enters the lung via the pulmonary ligament if the artery originates above the diaphragm. Arteries originating below the diaphragm reach the sequestration by piercing the diaphragm or via the aortic or esophageal hiatus.
In the rare instance of sequestration in an upper lobe, arterial supply from the internal thoracic artery has been reported. If aortography (seen in the images below) is unrevealing, a coronary source should be included in the preoperative search
 References

- Medscape
- Intralobar sequestration: a missed diagnose. The annals of thoracic Surgery


miércoles, 26 de octubre de 2011

Abnormal Uterine Bleeding - Williams Gynecology Review


Definitions
Hypermenorrea or menorragia: More than 80ml or 7 days of menstrual bleeding
Polymenorrea: Cycles lasting less than 21 days
Metrorragia: Intercycle bleeding

Childhood
Bleeding prior to menarche should be investigated as an abnormal finding. Initial evaluation should focus on determining the location of the bleeding, because vaginal, rectal, or urethral bleeding can present similarly. In this age group, the vagina, rather than the uterus, is the most common source of bleeding. Vulvovaginitis is the most frequent cause, but dermatologic conditions, neoplastic growths, or trauma by accident, abuse, or foreign body may also be reasons. In addition to vaginal sources, bleeding may also originate from the urethra and may reflect urethral prolapse or infection
Perimenopause
Abnormal uterine bleeding is a frequent clinical problem, accounting for 70 percent of all gynecologic visits by peri- and postmenopausal women. As with perimenarchal girls, anovulatory uterine bleeding from dysfunction of the hypothalamic-pituitary-ovarian axis becomes a more common finding in this group. Alternatively, the incidence of bleeding related to pregnancy and sexually transmitted disease decreases. With increasing age, there are greater risks of benign and malignant neoplastic growth.
Menopause
Bleeding after menopause typically originates from benign disease. For example, Choo and colleagues (1985) found that the majority of cases resulted from atrophy of the endometrium. Benign endometrial polyps may also cause bleeding in this population.
Pathophysiology
The endometrium consists of two distinct zones, the functionalis layer and the basalis layer (Fig. 8-2). The basalis layer stretches beneath the functionalis, lies in direct contact with the myometrium, and is less hormonally responsive. The basalis serves as a reservoir for the regeneration of the functionalis following menses. In contrast, the functionalis layer lines the uterine cavity, undergoes dramatic change throughout the menstrual cycle, and ultimately sloughs during menstruation. Histologically, the functionalis has a surface epithelium and underlying subepithelial capillary plexus. Beneath these are organized stroma and glands in which leukocyte populations are interspersed








Blood reaches the uterus via the uterine and ovarian arteries (Fig. 38-13). From these, the arcuate arteries are formed and supply the myometrium. These in turn branch into the radial arteries, which extend toward the endometrium at right angles from the arcuate arteries (see Fig. 8-2). At the endometrium-myometrium junction, the radial arteries bifurcate to create the basal and spiral arteries. The basal arteries serve the basalis layer of the endometrium and are relatively insensitive to hormonal changes (Abberton, 1999; Hickey, 2000b; Weston, 2000). The spiral arteries stretch to supply the functionalis layer. Their arteriole branches are thought to be critical in controlling menstruation. Prior to menses these arterioles display increased coiling with stasis of blood flow. Subsequently, vasodilatation and bleeding from the spiral arteriole and capillary walls ensues. As a result, most menstrual blood is lost through these vessels. This is followed by vasoconstriction which leads to endometrial ischemia and necrosis. This necrotic tissue is sloughed with menstruation.
Postcoital Bleeding
Bleeding following intercourse most commonly develops in women aged 20 to 40 years and in those who are multiparous. No underlying pathology is identified in up to two thirds (Rosenthal, 2001; Selo-Ojeme, 2004). If an identifiable lesion is found, however, it typically is benign (Shalini, 1998). In a review of 248 women with postcoital bleeding, Selo-Ojeme and co-workers (2004) found that a fourth of cases were caused by cervical eversion (see Chap. 29, Cervix). Other causes included endocervical polyps, cervicitis, and less commonly, endometrial polyps.
In some women, postcoital bleeding may be from cervical or other genital tract neoplasia. The epithelium associated with cervical intraepithelial neoplasia (CIN) and invasive cancer is thin and friable and readily detaches from the cervix. In women with postcoital bleeding, CIN was found in 7 to 10 percent, invasive cancer in about 5 percent, and vaginal or endometrial cancer in <1 percent.
Painful intercourse and noncyclic pain are less frequent in women with abnormal bleeding and usually suggests a structural or infectious cause. For example, Lippman and colleagues (2003) reported increased rates of dyspareunia and noncyclic pelvic pain in women with uterine leiomyomas. Similarly, Sammour and co-workers (2002) correlated increasing pelvic pain with deepening myometrial invasion with adenomyosis
The incidence and risk of endometrial carcinoma increases with age and three fourths of women with this malignancy are postmenopausal. Thus, in postmenopausal patients, the need to exclude cancer intensifies and endometrial biopsy is warranted. In the remaining 25 percent of premenopausal women with endometrial cancer, only 5 percent are less than 40 years of age (Peterson, 1968). Most of these premenopausal women are obese or have chronic anovulation, or both (Rose, 1996). Thus, obese or anovulatory women with abnormal bleeding should also have endometrial cancer excluded. The American College of Obstetricians and Gynecologists (2000) recommends endometrial assessment in any woman older than 35 years with abnormal bleeding and in those younger than 35 years who are suspected of having anovulatory uterine bleeding refractory to medical management.
Clinical Evaluation
Initially, the site of uterine bleeding must be confirmed because bleeding may also come from the lower reproductive tract, gastrointestinal system, or urinary tract. This is more difficult when there is no active bleeding. In these situations, urinalysis or stool guaiac evaluation may be helpful adjuncts to a thorough examination
Hematologic and B-HCG Testing
A hemogram is useful to evaluate anemia from chronic blood loss as well as the degree of blood loss in women with menorrhagia. An abnormally low serum ferritin level is a satisfactory predictor of blood loss >80 mL per menstrual cycle (Warner, 2004).
Pregnancy complications are quickly excluded with determination of urine or serum levels of human chorionic gonadotropin (-hCG). Miscarriages and ectopic pregnancies may cause simple spotting or lead to life-threatening hemorrhage.
Endometrial Biopsy
Sampling and histologic evaluation of the endometrium in women with abnormal bleeding may disclose infection or neoplastic lesions such as endometrial hyperplasia, cancer, polyps, or gestational trophoblastic neoplasia
For years, dilatation and curettage (D&C) was used for endometrial tissue sampling (see Section 41-16, Sharp Dilatation and Curettage). But because of the associated surgical risks, expense, postoperative pain, and need for operative anesthesia, other suitable substitutes were evaluated. In addition, several investigators have demonstrated high rates of incomplete sampling and missed pathology with D&C (Goldstein, 1997; Grimes, 1982; Stock, 1975).
Of suitable substitutes for D&C, office techniques using metal curettes were implemented to obtain endometrial samples, and these showed significant positive correlations with histologic results from hysterectomy specimens (Ferenczy, 1979; Stovall, 1989). The main disadvantages, however, were patient discomfort, cost, and procedural complications such as uterine perforation and infection. To minimize these, a variety of thin, flexible plastic samplers have been evaluated, with comparable histologic findings from tissues obtained by D&C, hysterectomy, or stiff metal curette (Stovall, 1991). In their meta-analysis of endometrial biopsy tools, Dijkhuizen and co-workers (2000) found the Pipelle (CooperSurgical, Trumbull, CT) to be superior
Despite its advantages, there are limitations to endometrial sampling with the Pipelle device. First, a tissue sample that is inadequate for histologic evaluation or an inability to pass the catheter into the endometrial cavity is encountered in up to 28 percent of biopsy attempts (Smith-Bindman, 1998). Cervical stenosis is the most common cause of obstruction. An incomplete evaluation necessitates further investigation with D&C, transvaginal sonography, or diagnostic hysteroscopy (Emanuel, 1995). Second, endometrial biopsy has a cancer-detection failure rate of 0.9 percent. Thus, a positive histologic result is accurate to diagnose cancer, whereas a negative result does not necessarily exclude it. Therefore, if an endometrial biopsy with normal tissue is obtained, but abnormal bleeding continues despite conservative treatment or if the suspicion of endometrial cancer is high, then further diagnostic efforts are warranted (Clark, 2002; Hatasaka, 2005). Finally, endometrial sampling is associated with a greater percentage of false-negative results if the pathology is focal, such as with endometrial polyps. Guido and associates (1995) reported false-negative results in 11 of 65 patients—17 percent—undergoing Pipelle endometrial sampling for abnormal bleeding. Five of these 11 had malignant tissue present only in endometrial polyps, and another three patients had disease localized to less than 5 percent of the endometrial surface. Because of these limitations with endometrial sampling, investigators have evaluated the use of sonography, hysteroscopy, or both to replace or complement endometrial sampling.
TVU
Although the thickness of the endometrium varies, ranges have been established. Granberg and co-workers (1991) found thickness measurements of 3.4 ± 1.2 mm in postmenopausal women with an atrophic endometrium, 9.7 ± 2.5 mm in those with endometrial hyperplasia, and 18.2 ± 6.2 mm in those with endometrial cancer. Subsequently, a number of investigations have focused on endometrial thickness as it relates to the risk of hyperplasia and cancer in postmenopausal women. Sensitivities of 95 to 97 percent have been reported using a measurement of >4 mm for exclusion of endometrial cancer. This guideline can be employed whether or not a patient is taking hormone replacement therapy (Bakour, 1999; Karlsson, 1995; Tsuda, 1997). Women with endometrial thicknesses >5 mm warrant additional evaluation with saline-infusion sonography (SIS), hysteroscopy, or endometrial biopsy.
Endometrial thickness guidelines, however, have not been established for premenopausal women. Merz and colleagues (1996) found that the normal endometrial thickness in premenopausal women did not exceed 4 mm on day 4 of the menstrual cycle, nor did it measure over 8 mm by day 8. In their review, Farquar and co-workers (1999) suggested that a persistent finding of endometrial thickness, independent of cycle day, measuring >12 mm should prompt further evaluation in these women, especially in those with risk factors for endometrial carcinoma (see Chap. 33). Risks include extended abnormal uterine bleeding, chronic anovulation, nulliparity, diabetes, obesity, hypertension, and tamoxifen use (Hatasaka, 2005).
Qualities other than endometrial thickness are also considered, and textural changes may indicate pathology. For example, punctate cystic areas within the endometrium may indicate a polyp. Conversely, hypoechoic masses that distort the endometrium and originate from the inner layer of myometrium most commonly are submucosal fibroids. Although there are no specific sonographic findings that are characteristic of endometrial cancer, some findings have been linked with greater frequency. For example, intermingled hypo- and hyperechoic areas within the endometrium may indicate malignancy. Endometrial cavity fluid collections and an irregular endometrial-myometrial junction have also been implicated. Thus, even with a normal endometrial stripe width, endometrial biopsy or hysteroscopy with biopsy should be performed to exclude malignancy when there is heterogeneous endometrial echogenicity or fluid collection.
A major limitation of TVS is the higher false-negative rate in diagnosing focal intrauterine pathology. This results in part from the physical inability of TVS to clearly assess the endometrium when there is concurrent uterine pathology such as leiomyomas or polyps. These women warrant either saline-infusion sonography or hysteroscopy for further evaluation.
To perform SIS, a small catheter is threaded through the cervical os into the endometrial cavity. Through this catheter, sterile saline is infused, and the uterus is distended. Sonography is then performed using a traditional transvaginal technique. Saline-infusion sonography (SIS) has also been compared with hysteroscopy to detect uterine cavitary focal lesions. De Kroon and co-workers (2003) performed a meta-analysis of 24 studies and reported SIS to equal the diagnostic accuracy of hysteroscopy.
Another disadvantage to SIS is that it is best performed in the proliferative phase of the cycle to minimize false-negative and false-positive results. For example, focal lesions may be concealed in a thick, secretory endometrium. Also, the amount of endometrial tissue that can develop during the normal secretory phase can be mistaken for small polyps or focal hyperplasia (Goldstein, 2004). For many, SIS has more patient discomfort than TVS, and about 5 percent of examinations cannot be completed because of cervical stenosis or patient discomfort. As expected, stenosis is more prevalent in postmenopausal women (De Kroon, 2003). This rate of incompletion mirrors that of diagnostic hysteroscopy. Although accurate for identifying focal lesions, SIS may not add to the value of TVS alone to evaluate diffuse lesions such as hyperplasia and cancer. Therefore, in postmenopausal women with abnormal bleeding, and in whom the exclusion of cancer is more relevant than evaluating focal intracavitary lesions, use of SIS as an initial diagnostic tool may not have advantages over TVS alone.
Histeroscopy: This procedure involves inserting an optic endoscope, usually 3 to 5 mm in diameter, into the endometrial cavity (see Section 41-35, Hysteroscopy). The uterine cavity is then distended with saline or another medium for visualization. In addition to inspection, biopsy of the endometrium allows histologic diagnosis of visually abnormal areas and has been shown to be a safe and accurate means to identify pathology (van Dongen, 2007). In fact, for many studies done to investigate the accuracy of TVS or SIS for evaluation of intracavitary uterine pathology, hysteroscopy is used as the gold standard for comparison.
The main advantage of hysteroscopy is to detect intracavitary lesions such as leiomyomas and polyps that might be missed using transvaginal sonography or endometrial sampling (Fig. 8-10) (Tahir, 1999). In fact, some have advocated hysteroscopy as the primary tool for the diagnosis of abnormal uterine bleeding. Although it is highly accurate for identifying endometrial cancer, it is less accurate for endometrial hyperplasia. Thus, some recommend endometrial biopsy or endometrial curettage in conjunction with hysteroscopy.
There are other limitations to hysteroscopy. Cervical stenosis sometimes will block successful introduction of the endoscope, and heavy bleeding may limit an adequate examination (Beukenholdt, 2003). The use of misoprostol, 100 mg orally the evening before and the morning of hysteroscopy, is useful for cervical softening in patients with suspected cervical stenosis. Hysteroscopy is more expensive and technically challenging than TVS or SIS. Many perform hysteroscopy in their office, whereas others prefer a day-surgery setting to provide increased patient analgesia. Obviously, greater cost and anesthetic risks can attend completion in this latter setting. Although it can be painful, use of a 3.5-mm minihysteroscope instead of the conventional 5-mm endoscope significantly decreases patient discomfort during office hysteroscopy (Cicinelli, 2003). Associated infection and uterine perforation have been reported with hysteroscopy, but fortunately their incidence is low.
There is concern that peritoneal seeding with malignant cells may take place during hysteroscopy in some women subsequently diagnosed with endometrial cancer (Obermair, 2000; Zerbe, 2000). Caution is advised with hysteroscopy in women at high risk for endometrial cancer, and some suggest a negative endometrial biopsy result is necessary before hysteroscopy is done (Oehler, 2003). Although there may be a risk of peritoneal contamination by cancer cells with hysteroscopy, there is no evidence that the prognosis for patients is worsened.
There is no one clear sequence to use of endometrial biopsy, TVS, SIS, and hysteroscopy when evaluating abnormal uterine bleeding. None of these will distinguish all anatomic lesions with high sensitivity and specificity. That said, TVS for several reasons is a logical first step. It is well-tolerated, cost-effective, and requires relatively minimal technical skill. Additionally, it has the advantage of reliably determining whether a lesion is diffuse or focal. Once anatomic lesions have been identified, subsequent evaluation requires individualization. If endometrial hyperplasia or cancer is suspected, then endometrial biopsy may offer advantages. Alternatively, possible focal lesions may be best investigated with either hysteroscopy or SIS. Ultimately, the selection of appropriate tests depends on their accuracy to characterize the most likely anatomic lesions.
Copper-Containing Intrauterine Device
These intrauterine devices (IUDs) have long been associated with menorrhagia and metrorrhagia (see Chap. 5, Menorrhagia) (Milsom, 1995; Bilian, 2002). Several explanations for this bleeding have been suggested. At the cellular level, unbalanced ratios of prostaglandins and thromboxane have been proposed as a potential source of IUD-induced menorrhagia
Initially, patients with IUD-related bleeding may be managed with empiric trials of NSAIDs (Table 8-3). Persistent abnormal bleeding, however, may result from other gynecologic pathology and not from the IUD. These patients should be managed similarly to other women with the complaint of abnormal uterine bleeding. Although sonographic evaluation may be limited by IUD shadowing, endometrial biopsy with small catheters can be performed without removal of the device.
This system, marketed as Mirena (Berlex, Wayne, NJ) (see Fig. 5-5), can lead to abnormal uterine bleeding in some users.
Combination Hormonal Contraception
Bleeding associated with combination oral contraceptive pills (COCs) is common (see Chap. 5, Estrogen Plus Progestin Contraceptives). As many as 30 to 50 percent of women experience abnormal uterine bleeding in the first month that they use combination COCs (Hatcher, 2004). The presumed source of this bleeding stems from endometrial atrophy, which is induced by the progestin component of COCs. During this process, spiral arterioles do not characteristically coil, and they become thinner and more sinusoidal. In addition, venules become dilatated and prone to thrombosis. This often leads to local tissue infarction and is thought to be the cause of breakthrough bleeding
Tamoxifen
This selective estrogen receptor modulator (SERM) is used as an adjunct for treatment of estrogen-receptor–positive breast cancer. Although it diminishes estrogen action in breast tissue, its effects on the endometrium stimulate proliferation (see Chap. 12, Breast Cancer Prevention). Tamoxifen use has been linked to endometrial hyperplasia, polyps, and carcinoma as well as uterine sarcomas (Cohen, 2004).
Screening women who use tamoxifen and do not have abnormal bleeding has not proved effective. Protocols using sonography or endometrial biopsy failed to effectively identify endometrial cancer in asymptomatic users (Barakat, 2000; Love, 1999). As a result, women using tamoxifen should undergo evaluation for endometrial cancer only when bleeding develops
Dysfunctional Uterine Bleeding
Once organic causes of abnormal uterine bleeding have been excluded, the term dysfunctional uterine bleeding (DUB) is used. Up to one-half of women with abnormal bleeding will have DUB (Hickey, 2000b). In 80 to 90 percent of these, bleeding results from dysfunction of the hypothalamic-pituitary-ovarian axis, which leads to anovulation (see Chap. 16). Because anovulatory cycles produce no progesterone to stabilize cyclic withdrawal of the estrogen-prepared endometrium, bleeding episodes become irregular and amenorrhea, metrorrhagia, and menorrhagia are common. For example, many women with anovulation may have amenorrhea for weeks to months followed by irregular, prolonged, and heavy bleeding.
In the other 10 to 20 percent of women with DUB, ovulation occurs cyclically, and menorrhagia is thought to originate from defects in the control mechanisms of menstruation.
Anovulatory DUB
No progesterone is produced when ovulation does not occur, and thus proliferative endometrium persists. At the tissue level, presistent proliferative endometrium is often associated with stromal breakdown, decreased spiral arteriole density, and increased dilated and unstable venous capillaries (Singh, 2005). At the cellular level, the availability of arachidonic acid is reduced, and prostaglandin production is impaired. For these reasons, bleeding associated with anovulation is thought to result from changes in endometrial vascular structure and in prostaglandin concentration, and from an increased endometrial responsiveness to vasodilating prostaglandins
Ovulatory DUB
Whereas anovulatory DUB results from alterations in vascular architecture and tone, ovulatory DUB is thought to stem predominantly from vascular dilatation alone. For example, women with ovulatory bleeding lose blood at rates three times faster than women with normal menses, but the number of spiral arterioles is not increased (Abberton, 1999). Thus in women with ovulatory DUB, it is thought that the vessels supplying the endometrium have decreased vascular tone and therefore increased rates of blood loss resulting from vasodilatation (Rogers, 2003). A number of causes that provoke this change in vascular tone have been suggested, and prostaglandins have been strongly implicated
Nonsteroidal Anti-Inflammatory Drugs
These medicines are effective and well-tolerated oral agents commonly used for the treatment of DUB (see Table 8-3). The rationale for their use stems from the suspected role of prostaglandins in the pathogenesis of DUB. A number of investigators have documented the effectiveness of NSAIDs in decreasing DUB-related menorrhagia (Makarainen, 1986b; Marchini, 1995). Among NSAIDs, there are no differences in clinical efficacy,
Women lose 90 percent of menstrual blood volume during the first 3 days of menses (Haynes, 1977). Accordingly, NSAIDs are most effective if used with the onset of menses or just prior to its onset and continued throughout its duration. Therefore, one advantage to NSAIDs is that they are required only during menstruation. Another advantage is that commonly associated dysmenorrhea also improves with NSAIDs.
The so-called "conventional" NSAIDs nonspecifically inhibit both cyclooxygenase-1 (COX-1), an enzyme critical to normal platelet function, and COX-2, which mediates inflammatory response mechanisms. They are effective analgesics, but their use with bleeding may not be ideal considering their inhibitory effects on platelet function. The other class of NSAIDs inhibits only COX-2 and does not interfere with platelet aggregation and hemostasis (Leese, 2000). Some have proposed that COX-2 inhibitors might be more effective to treat menorrhagia, however, there have been no randomized trials that validate this idea (Hayes, 2002). Additionally, there are now concerns that long-term use of COX-2 inhibitors is associated with increased myocardial infarction, stroke, and heart failure (Solomon, 2005). As a result, further investigation is needed before routine use of COX-2 inhibitors is recommended for menorragia.
Tranexamic Acid
This is an antifibrinolytic drug that exerts its effects by reversibly blocking lysine binding sites on plasminogen. The resulting decreased plasmin levels diminish fibrinolytic activity within endometrial vessels to prevent bleeding. The drug has no effect on other blood coagulation parameters such as platelet count, activated partial thromboplastin time, and prothrombin time (Wellington, 2003).
In women with DUB, there is increased fibrinolytic activity within the endometrium compared with women with normal menses (Gleeson, 1994). Clinically, the drug has been shown effective to reduce bleeding in up to half of women with DUB-related menorrhagia (Coulter, 1995; Lethaby, 2000). In addition, tranexamic acid requires administration only during menstruation and has few minor reported side effects. These are predominantly gastrointestinal and dose-dependent.
Oral Progestins
As discussed earlier, unopposed estrogen stimulation, resulting from anovulatory cycles, causes proliferation of the endometrium and erratic bleeding. Progestins halt endometrial growth and allow for an organized sloughing with their withdrawal (Saarikoski, 1990). Thus, progestin treatment of women with anovulatory DUB is usually successful. Of the oral progestins, either norethindrone—also known as norethisterone—or medroxyprogesterone acetate may be used. For immediate control of bleeding, norethindrone, 5 mg, is given two or three times daily, or medroxyprogesterone acetate 10 mg is taken once daily for 10 days. This is followed by withdrawal bleeding 3 to 5 days after completion of the either course. For long-term management, similar dosages of these drugs are given during days 16 through 25 following commencement of the most recent menstrual flow (Fraser, 1990). Again, withdrawal bleeding will follow cessation each month
In contrast, ovulatory menorrhagia is not due to a progestin deficiency but may result from altered prostaglandin synthesis or disruption of hemostasis. As expected, ovulatory menorrhagia is relatively unresponsive to cyclic administration of oral progestins (Cameron, 1987, 1990; Preston, 1995; Singh, 2005).
Despite this, women with ovulatory DUB may respond to longer treatment schedules. Norethindrone 5 mg or medroxyprogesterone acetate 10 mg, each given three times orally daily for days 5 to 26 of each menstrual cycle have been shown effective (Fraser, 1990; Irvine, 1998). Unfortunately, prolonged use of high-dose progestins is often associated with side effects such as mood changes, weight gain, bloating, headaches, and atherogenic changes in the lipid profile (Lethaby, 1998b). For these reasons, they are considered unacceptable by many women for long-term use
Combination Oral Contraceptive Pills
Evidence suggests that these hormonal contraceptives are effective in the treatment of DUB, and when used long term, reduce flow by 40 to 70 percent (Agarwal, 2001; Fraser, 1991). Advantages to COC use include the additional benefits of reducing dysmenorrhea and providing contraception (see Chap. 5, Estrogen Plus Progestin Contraceptives). Their presumed method of action is endometrial atrophy. There may also be diminished prostaglandin synthesis and decreased endometrial fibrinolysis (Irvine, 1999).
In addition to chronic use for the treatment of dysfunctional uterine bleeding, COCs can be used acutely to manage menorrhagia. Pills containing at least 30 ug of ethinyl estradiol should be prescribed. If there is active bleeding, the regimen begins with four pills every 6 hours until the bleeding has stopped for at least 24 hours. An antiemetic may be needed to control nausea. For most women, bleeding will cease within 48 hours. After the bleeding has stopped, the dosage of COC is decreased to three pills per day for the next 3 days, followed by two pills per day for 3 days. A once-a-day regimen is then continued for 21 days to be followed by withdrawal menses. At this point, COCs may be stopped or continued for cycle control (Rimsza, 2002). Alternatively, less frequent dosing or smaller doses may also be effective in the acute management of menorrhagia
Androgens (Danazol and Gestrinone)
Danazol is an isoxazole derivative of the synthetic steroid 17-ethinyl testosterone (see Chap, 10, Androgens). The net effect of danazol creates a hypoestrogenic and hyperandrogenic environment, which induces endometrial atrophy. As a result, menstrual loss is reduced by approximately half, and it may even induce amenorrhea in some women (Beaumont, 2002; Chimbira, 1980a; Higham, 1993).
For heavy menstrual bleeding, suggested dosing is 100 to 200 mg taken orally every day (Chimbira, 1980b). Unfortunately, this agent has significant androgenic side effects that include weight gain, oily skin, and acne. It is thus usually reserved as a second-line drug for short-term use prior to surgery
Estrogens, GNH agonists
Levonorgestrel-Containing Intrauterine System
Intrauterine devices were developed for contraceptive purposes, but the levonorgestrel-containing intrauterine system (LNG-IUS) also provides relief of menorrhagia for some women (see Chap. 5, Levonorgestrel-Containing Intrauterine Device
The LNG-IUS can be used in all women as a first line of treatment of menorrhagia in place of oral medications. It is particularly useful for reproductive-aged women who also desire contraception
Dilatation and Curettage (D&C)
Curettage is rarely used for long-term treatment because its effects are only temporary. In the occasional woman, D&C is performed to arrest severe bleeding refractory to high-dose estrogen administration
Endometrial Destructive Procedures
Although medical therapy is generally used first, over half of women with menorrhagia undergo hysterectomy within 5 years of referral to a gynecologist. In at least a third of these, an anatomically normal uterus is removed (Coulter, 1991; Roy, 2004). As alternatives to hysterectomy, less invasive procedures have been devised that either destroy or resect the endometrium and lead to amenorrhea in a manner similar to Asherman syndrome
It is problematic that endometrial tissue has tremendous regenerative capabilities. For this reason, to be successful, destructive procedures must remove the endometrial functionalis and basalis as well as 3 mm of myometrial depth. However, the persistence or regeneration of endometrium is possible. Therefore, premenopausal women should be counseled before surgery about the need for adequate postoperative contraception.
In addition, the American College of Obstetricians and Gynecologists (2007) recommends endometrial sampling prior to surgery. Women with endometrial hyperplasia or cancer should not undergo ablation
Both first- and second-generation procedures require dilation of the cervix to admit the ablative device. They are typically performed using general anesthesia or conduction analgesia. However, some have described the use of paracervical block and/or intravenous sedation for second-generation procedures (Fernandez, 1997; Soysal, 2001; Wallage, 2003). Recently, Marsh and co-workers (2005) described the use of thermal balloon ablation using only preoperative ibuprofen.
HIsterectomy
Müllerian Defects
Congenital structural lesions of the reproductive tract may at times cause chronic intermenstrual bleeding superimposed upon normal menstrual cycles (see Chap. 18, Description and Patient Presentation). In such cases, an anomalous partial vaginal septum may collect blood behind it. Although sequestered, a small patent outflow from the collection typically allows chronic release. Patients thus describe cyclic menses with light but persistent intermenstrual flow
Endometrial Polyp
These soft, fleshy intrauterine overgrowths are comprised of endometrial glands and fibrotic stroma and are covered by a surface epithelium (Fig. 8-10 and 8-11). Polyps are common, and their prevalence ranges from 10 to 30 percent in women with abnormal bleeding (Bakour, 2000; Goldstein, 1997). As shown in Figure 8-11, intact polyps may be single or multiple, may measure from a few millimeters to several centimeters, and may be sessile or pedunculated with a long and slender stalk (Kim, 2004). Most polyps are benign, but hyperplasia develops frequently. Moreover, malignant transformation develops in 1 to 2 percent of polyps
More than 70 percent of women with endometrial polyps will complain of menorrhagia or metrorrhagia (Preutthipan, 2005; Reslova, 1999). It is thought that stromal congestion within the polyp leads to venous stasis with apical necrosis and bleeding (Jakab, 2005). Although bleeding is common, with the introduction of transvaginal sonography, a large number of women with asymptomatic polyps have been identified during imaging for other indications
The few risk factors associated with development of endometrial polyps include hypertension and obesity as well as tamoxifen use (Reslova, 1999). Most evidence does not support a link between hormone replacement therapy and polyp formation.
Once a polyp has been identified, operative hysteroscopy is often the treatment of choice. The technique is detailed in Section 41-38, Polypectomy. Hysteroscopy and polypectomy is recommended for symptomatic women or for those with risk factors for malignant transformation (Savelli, 2003; Machtinger, 2005). Conversely, asymptomatic premenopausal women with polyps <1.5 cm can be observed. There is only a small associated risk of malignant transformation and high rates of spontaneous resolution.
Endocervical Polyp
These lesions represent overgrowths of benign endocervical stroma covered by epithelium. They appear as single, red, smooth elongated masses extending from the external os (see Fig. 4-13). Polyps vary in size and range from several millimeters to 2 or 3 cm. These common growths are found more frequently in multiparas and rarely in prepubertal females. Endocervical polyps are typically asymptomatic, but they can cause metrorrhagia, postcoital bleeding, and symptomatic vaginal discharge.
Endocervical polyps are usually identified by visual inspection during pelvic examination. In some instances, Pap smear findings of atypical glandular cells have been associated with endocervical polyps (Burja, 1999; Obenson, 2000). Although typically benign, malignant transformation may develop in 1 percent. Importantly, cervical cancer can present as polypoid masses and can mimic these benign lesions. For this reason, removal and histologic evaluation are recommended for an endocervical polyp.
Endocervical polyps are removed by grasping the polyp with a ring or polyp forceps. The polyp is twisted repeatedly about the base of its stalk to strangulate its feeding vessels. With repeated twisting the base will avulse. Monsel solution (ferric subsulfate) can be applied with direct pressure to the resulting stalk stub to complete hemostasis
VWD: Treatments for women with menorrhagia and vWD include desmopressin, plasma concentrates, hormonal contraception, antifibrinolytics, and surgery. Combination oral contraceptive pills have been noted to arrest uterine hemorrhage in 88 percent of women (Foster, 1995). Also, Kingman and co-workers (2004) reported that the LNG-IUS effectively decreased blood loss and induced amenorrhea in 56 percent of women with inherited bleeding disorders. Preliminary success has been found with endometrial ablation for women with vWD-related menorrhagia (El-Nashar, 2007; Rubin, 2004). Hysterectomy, of course, is curative and preoperative consultation with a hematologist is recommended