From: Subject: Lymphedema - National Cancer Institute Date: Tue, 3 Mar 2009 22:45:02 +0100 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C99C51.B0D31F80" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3350 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C99C51.B0D31F80 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.cancer.gov/cancertopics/pdq/supportivecare/lymphedema/HealthProfessional/page2 =EF=BB=BF Lymphedema - National Cancer Institute
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Overview

Introduction
Anatomy=20 and Pathophysiology of the Lymphatic System
Clinical=20 = Manifestations
        Psychological=20 symptoms
Epidemiology
Risk=20 = Factors
        Axillary=20 node=20 = removal
        Sentinel=20 node=20 = biopsy
        Obesity
   &nb= sp;    Other
Diagnosis=20 and Evaluation



Introduction

Lymphedema is swelling that occurs when = protein-rich=20 lymph fluid accumulates in the interstitial tissue. This = lymph fluid=20 may contain plasma proteins, extravascular blood cells, = excess=20 water, and parenchymal products.[1]=20 Lymphedema is one of the most poorly understood, relatively=20 underestimated, and least researched complications of cancer = or its=20 treatment. The Institute of Medicine of the National = Academies=20 published a report in 2006 recommending a = =E2=80=9Csurvivorship care plan=E2=80=9D=20 for cancer patients that incorporates information about late = effects=20 of treatment, health management behaviors, disease = management, and=20 recurrence monitoring.[2]=20 The Institute of Medicine also highlighted critical = shortfalls in=20 the transition to survivorship, particularly in providing = education=20 about late effects of treatment.

Lymphedema is an important consideration for = clinicians who care for cancer patients because of its = relatively=20 high frequency and significant functional and quality of = life=20 implications for patients. Lymphedema is an independent = predictor of=20 decreased quality of life, even when other predictive = factors such=20 as socioeconomic status, decreased range of motion, age, and = obesity=20 are taken into account.[3]

This summary will review issues related to = anatomy and=20 pathophysiology of lymphedema related to cancer, its = clinical=20 manifestations, diagnosis, and treatment. Primary = (congenital)=20 lymphedema and non=E2=80=93cancer-related lymphedema (i.e., = recurrent=20 cellulitis, connective tissue disease, and infection) will = not be=20 reviewed here.

Anatomy and=20 Pathophysiology of the Lymphatic System

The human lymphatic system generally = includes=20 superficial or primary lymphatic vessels that form a complex = dermal=20 network of capillarylike channels that drain into larger, = secondary=20 lymphatic vessels located in the subdermal space. These = primary and=20 secondary lymphatic vessels parallel the superficial veins = and drain=20 into a deeper third layer of lymphatic vessels located in = the=20 subcutaneous fat adjacent to the fascia. A muscular wall and = numerous valves aid active, unidirectional lymphatic flow in = secondary and subcutaneous lymphatic vessels. Primary = lymphatic=20 vessels lack a muscular wall and do not have valves. An=20 intramuscular system of lymphatic vessels that parallels the = deep=20 arteries and drains the muscular compartment, joints, and = synovium=20 also exists. The superficial and deep lymphatic systems = probably=20 function independently, except in abnormal states, although = there is=20 evidence that they communicate near lymph nodes.[4]=20 Lymph drains from the lower limbs into the lumbar lymphatic = trunk,=20 which joins the intestinal lymphatic trunk and cisterna = chyli to=20 form the thoracic duct that empties into the left subclavian = vein.=20 The lymphatic vessels of the left arm drain into the left = subclavian=20 lymphatic trunk and then into the left subclavian vein. = Lymph=20 channels of the right arm drain into the right subclavian = lymphatic=20 trunk and then into the right subclavian vein.

One function of the lymphatic system is to = return=20 excess fluid and protein from interstitial spaces to the = blood=20 vascular system. Because lymphatic vessels often lack a = basement=20 membrane, they can resorb molecules too large for venous = uptake.=20 Mechanisms of clinical edema include increased arteriovenous = capillary filtration and reduced interstitial fluid = absorption.=20 Causes of increased capillary filtration include increased=20 hydrostatic pressure in capillaries, decreased tissue = pressure, and=20 increased membrane permeability. Reduced interstitial fluid=20 resorption can be caused by decreased plasma oncotic = pressure,=20 increased oncotic pressure of tissue fluid, and lymphatic=20 obstruction.

Clinical=20 Manifestations

The onset of secondary lymphedema is often = insidious.=20 However, it may be suddenly provoked by local inflammation = from=20 causes such as infection or limb injury. Therefore, patients = should=20 be evaluated for evidence of cellulitis. Classically, = lymphedema is=20 characterized by nonpitting swelling of an extremity, = usually with=20 involvement of the digits. Early stages of lymphedema = manifest with=20 pitting edema until fibrosis develops. The distribution of = the=20 swelling may be restricted only in the proximal or distal = portion of=20 the limb. Lymphedema may also predispose to recurrent skin=20 infections.[5]

Patients with lymphedema may report a wide = variety of=20 complaints: heaviness or fullness related to the weight of = the limb,=20 a tight sensation of the skin, or decreased flexibility of = the=20 affected joint. The texture of the skin may become = hyperkeratotic,=20 with verrucous and vesicular skin lesions. With upper = extremity=20 involvement, the patient may have difficulty fitting the = affected=20 area into clothing or wearing previously well-fitting rings, = watches, or bracelets. Similar difficulties with lower = extremity=20 lymphedema include a sensation of tightness or difficulty = wearing=20 shoes, itching of the legs or toes, burning sensation in the = legs,=20 or sleep disturbance and loss of hair. Ambulation can be = affected=20 because of the increased size and weight of the affected = limb.=20 Activities of daily living, hobbies, and the ability to = perform=20 previous work tasks may also be affected.

Psychological=20 symptoms

Breast cancer survivors with arm lymphedema = have been=20 found to be more disabled, experience a poorer quality of = life, and=20 have more psychological distress than do survivors without=20 lymphedema.[6,7]=20 In addition, women reporting swelling have reported = significantly=20 lower quality of life with multiple functional = assessments.[8]

Epidemiology

Lymphedema can occur after any cancer or its = treatment=20 that affects lymph node drainage. It has been reported to = occur=20 within days and up to 30 years after treatment for breast = cancer.[9]=20 Eighty percent of patients experience onset within 3 years = of=20 surgery; the remainder develop edema at a rate of 1% per = year.[10]=20 Upper-extremity lymphedema most often occurs after breast = cancer;=20 lower-extremity lymphedema most often occurs with uterine = cancer,=20 prostate cancer, lymphoma, or melanoma.[1]=20 A large population-based study supports the evidence that = lower-limb=20 lymphedema is experienced by a significant proportion of = women after=20 treatment for gynecological cancer, with the highest = prevalence=20 (36%) among vulvar cancer survivors and lowest prevalence = (5%) among=20 ovarian cancer survivors.[11]

There is no consistency in the data on the = incidence=20 and prevalence of lymphedema after breast cancer, probably = because=20 of differences in diagnosis, the different characteristics = of the=20 patients studied, and inadequate follow-up to capture = delayed=20 development of the disorder. The overall incidence of arm = lymphedema=20 can range from 8% to 56% at 2 years postsurgery.[8]

Risk = Factors

Patients undergoing axillary surgery and/or = axillary=20 radiation therapy for breast cancer are at higher risk for=20 developing lymphedema of the arm. Previous convention = suggested that=20 nodal positivity was a predisposing factor for the = development of=20 lymphedema in breast cancer patients.[12]=20 Controlling for axillary radiation, one study actually found = an=20 inverse relationship between nodal positivity and arm = volume.[12]

Axillary node=20 removal

Compared with axillary sampling alone, = partial or=20 total mastectomy followed by full axillary lymph node = dissection=20 significantly increases a patient=E2=80=99s chance of = developing arm edema.=20 For example, in one series of 100 women who underwent = partial or=20 total mastectomy and then full axillary lymph node = dissection or=20 axillary sampling, arm edema developed in more patients who=20 underwent axillary lymph node dissection compared with = sampling=20 alone (30% vs. none).[13]=20 In addition, the extent of axillary lymph node dissection = increases=20 the risk for developing arm edema. For example, in one = series=20 involving 381 women undergoing segmental mastectomy and = axillary=20 lymph node dissection, women who had ten or more lymph nodes = removed=20 were more likely than women who had few lymph nodes in the = specimen=20 to develop arm symptoms within the first year (53% vs. 33%) = and=20 within the next 2 years (33% vs. 20%).[14]

Sentinel node=20 biopsy

For patients with breast cancer, sentinel = lymph node=20 dissection has gained favor over axillary lymph node = dissection for=20 the axillary staging of early disease because of decreased = morbidity=20 and because of the questionable survival benefits of = axillary lymph=20 node dissection, as shown in a phase III randomized study = (ACOSOG-Z0011)=20 of axillary lymph node dissection in women who had stage I = or IIA=20 breast cancer and a positive sentinel node.[15]=20 Several studies have shown that lymphedema is more prevalent = in=20 breast cancer patients who undergo axillary lymph node = dissection=20 than in those who undergo sentinel lymph node biopsy.[16]=20 One study evaluated 30 patients with unilateral invasive = breast=20 carcinoma who underwent sentinel lymph node biopsy and 30 = patients=20 who underwent axillary lymph node dissection. This study = found a 20%=20 rate of developing lymphedema in the axillary lymph node = dissection=20 group compared with none in the sentinel lymph node biopsy = group.[16]

Obesity =

Among all breast cancer patients, being = obese or=20 overweight may predispose women to developing lymphedema = after=20 treatment for breast cancer.[9]=20 Some studies have correlated the degree of lymphedema with = the level=20 of obesity.[9]=20 Similarly, among young breast cancer survivors, persistent = swelling=20 was related to having more lymph nodes removed and being = obese.[8]

Other

Other risk factors for developing lymphedema = include=20 the following:

  • Extent of local = surgery.

  • Local radiation (axillary, = inguinal,=20 pelvic, or supraclavicular regions).

  • Delayed wound = healing.

  • Tumor causing lymphatic = obstruction=20 of the anterior cervical, thoracic, axillary, pelvic, or = abdominal=20 nodes.

  • Scarring of the left or = right=20 subclavian lymphatic ducts by either surgery or = radiation.

  • Intrapelvic or = intra-abdominal tumors=20 that involve or directly compress lymphatic vessels and/or = the=20 cisterna chyli and thoracic duct.

Diagnosis and=20 Evaluation

Lymphedema is typically evident by clinical = findings=20 such as nonpitting edema, usually with involvement of the = digits, in=20 a patient with known risk factors such as previous axillary=20 dissection. Other causes of limb swelling, including deep = venous=20 thrombosis, malignancy, and infection, should be considered = in the=20 differential diagnosis and excluded with appropriate = studies, if=20 indicated.

If the diagnosis is not evident on the basis = of=20 clinical assessment, imaging of the lymphatic system with=20 lymphoscintigraphy (radionuclide imaging) may be necessary.=20 Lymphangiography is generally no longer a favored diagnostic = test=20 and may be contraindicated in patients with malignancy = because of=20 concern that it may contribute to metastatic spread of = tumor.=20 Additional imaging techniques such as magnetic resonance = imaging may=20 complement information obtained via lymphoscintigraphy by = providing=20 anatomic and nodal detail.[17]

The wide variety of methods described in the = literature for evaluating limb volume and lack of = standardization=20 makes it difficult for the clinician to assess the at-risk = limb.=20 Options include water displacement, tape measurement, = infrared=20 scanning, and bioelectrical impedance measures.[18]

The most widely used method to diagnose = upper=20 extremity lymphedema is circumferential upper extremity = measurement=20 using specific anatomical landmarks.[5]=20 Arm circumference measures are used to estimate volume = differences=20 between the affected and unaffected arms. Sequential = measurements=20 are taken at four points on both arms: the = metacarpal-phalangeal=20 joints, the wrist, 10 cm distal to the lateral epicondyles, = and 15=20 cm proximal to the lateral epicondyles. Differences of 2 cm = or more=20 at any point compared with the contralateral arm are = considered by=20 some experts to be clinically significant. However, = measuring=20 specific differences between arms may have limited clinical=20 relevance because of implications, for example, of a 3-cm = difference=20 between the arm of an obese woman and the arm of a thin = woman. In=20 addition, there can be inherent anatomic variations in = circumference=20 between the dominant and nondominant limb related to = differences in=20 muscle mass and variations after breast cancer treatment = that may=20 occur with atrophy of the ipsilateral arm or hypertrophy of = the=20 contralateral arm.[3]=20 A small study comparing various methods of assessing upper = limb=20 lymphedema did not show any superiority of any one = method.[18]=20 Sequential measurements over time, including pretreatment=20 measurements, may prove to be more clinically = meaningful.

The water displacement method is another way = to=20 evaluate arm edema. A volume difference of 200 mL or more = between=20 the affected and opposite arms is typically considered to be = a=20 cutoff point to define lymphedema.[19]

One common method of lymphedema = classification uses=20 three stages based on severity.[5]=20 Stage I is spontaneously reversible and typically is marked = by=20 pitting edema, increase in upper extremity girth, and = heaviness.=20 Stage II is characterized by a spongy consistency of the = tissue=20 without signs of pitting edema. Tissue fibrosis can then = cause the=20 limbs to harden and increase in size.[5]=20 Stage III, also called lymphostatic elephantiasis, is the = most=20 advanced stage, but is rarely seen following breast cancer=20 treatment.[5]

References

  1. Meneses KD, McNees MP: = Upper=20 extremity lymphedema after treatment for breast cancer: a = review=20 of the literature. Ostomy Wound Manage 53 (5): 16-29, = 2007. =20 [PUBMED = Abstract]

  2. Hewitt M, Ganz PA, eds.: = From Cancer=20 Patient to Cancer Survivor - Lost in Transition: An = American=20 Society of Clinical Oncology and Institute of Medicine = Symposium.=20 Washington, DC: The National Academies Press, 2006. =20

  3. Petrek JA: Commentary: = prospective=20 trial of complete decongestive therapy for upper extremity = lymphedema after breast cancer therapy. Cancer J 10 (1): = 17-9,=20 2004. 

  4. Horsley JS, Styblo T: = Lymphedema in=20 the postmastectomy patient. In: Bland KI, Copeland EM, = eds.: The=20 Breast: Comprehensive Management of Benign and Malignant = Diseases.=20 Philadelphia, Pa: Saunders, 1991, pp 701-6.  =

  5. Bicego D, Brown K, Ruddick = M, et al.:=20 Exercise for women with or at risk for breast = cancer-related=20 lymphedema. Phys Ther 86 (10): 1398-405, 2006.  [PUBMED = Abstract]

  6. Pyszel A, Malyszczak K, = Pyszel K, et=20 al.: Disability, psychological distress and quality of = life in=20 breast cancer survivors with arm lymphedema. Lymphology 39 = (4):=20 185-92, 2006.  [PUBMED = Abstract]

  7. Ridner SH: Quality of life = and a=20 symptom cluster associated with breast cancer = treatment-related=20 lymphedema. Support Care Cancer 13 (11): 904-11, = 2005.  [PUBMED = Abstract]

  8. Paskett ED, Naughton MJ, = McCoy TP, et=20 al.: The epidemiology of arm and hand swelling in = premenopausal=20 breast cancer survivors. Cancer Epidemiol Biomarkers Prev = 16 (4):=20 775-82, 2007.  [PUBMED = Abstract]

  9. Shaw C, Mortimer P, Judd = PA:=20 Randomized controlled trial comparing a low-fat diet with = a=20 weight-reduction diet in breast cancer-related lymphedema. = Cancer=20 109 (10): 1949-56, 2007.  [PUBMED = Abstract]

  10. Petrek JA, Senie RT, = Peters M, et=20 al.: Lymphedema in a cohort of breast carcinoma survivors = 20 years=20 after diagnosis. Cancer 92 (6): 1368-77, 2001.  [PUBMED = Abstract]

  11. Beesley V, Janda M, Eakin = E, et al.:=20 Lymphedema after gynecological cancer treatment : = prevalence,=20 correlates, and supportive care needs. Cancer 109 (12): = 2607-14,=20 2007.  [PUBMED = Abstract]

  12. Purushotham AD, Bennett = Britton TM,=20 Klevesath MB, et al.: Lymph node status and breast = cancer-related=20 lymphedema. Ann Surg 246 (1): 42-5, 2007.  [PUBMED = Abstract]

  13. Borup Christensen S, = Lundgren E:=20 Sequelae of axillary dissection vs. axillary sampling with = or=20 without irradiation for breast cancer. A randomized trial. = Acta=20 Chir Scand 155 (10): 515-9, 1989.  [PUBMED = Abstract]

  14. Liljegren G, Holmberg L: = Arm=20 morbidity after sector resection and axillary dissection = with or=20 without postoperative radiotherapy in breast cancer stage = I.=20 Results from a randomised trial. Uppsala-Orebro Breast = Cancer=20 Study Group. Eur J Cancer 33 (2): 193-9, 1997.  [PUBMED = Abstract]

  15. Lucci A, McCall LM, = Beitsch PD, et=20 al.: Surgical complications associated with sentinel lymph = node=20 dissection (SLND) plus axillary lymph node dissection = compared=20 with SLND alone in the American College of Surgeons = Oncology Group=20 Trial Z0011. J Clin Oncol 25 (24): 3657-63, 2007.  [PUBMED = Abstract]

  16. Celebioglu F, Perbeck L, = Frisell J,=20 et al.: Lymph drainage studied by lymphoscintigraphy in = the arms=20 after sentinel node biopsy compared with axillary lymph = node=20 dissection following conservative breast cancer surgery. = Acta=20 Radiol 48 (5): 488-95, 2007.  [PUBMED = Abstract]

  17. Rockson SG: Lymphedema. Am = J Med 110=20 (4): 288-95, 2001.  [PUBMED = Abstract]

  18. Ridner SH, Montgomery LD, = Hepworth=20 JT, et al.: Comparison of upper limb volume measurement = techniques=20 and arm symptoms between healthy volunteers and = individuals with=20 known lymphedema. Lymphology 40 (1): 35-46, 2007.  [PUBMED = Abstract]

  19. Mondry TE, Riffenburgh RH, = Johnstone=20 PA: Prospective trial of complete decongestive therapy for = upper=20 extremity lymphedema after breast cancer therapy. Cancer J = 10 (1):=20 42-8; discussion 17-9, 2004 Jan-Feb.  [PUBMED=20 Abstract]

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Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .search-field { WIDTH: 120px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, "Trebuchet = MS", Tahoma, sans-serif; HEIGHT: 22px } .leftnav { FONT-SIZE: 11px; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } .box-title { FONT-WEIGHT: bold; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif; BACKGROUND-COLOR: #e6e6e2; = TEXT-DECORATION: none } A.box-title { FONT-WEIGHT: bold; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif; BACKGROUND-COLOR: #e6e6e2; = TEXT-DECORATION: none } A.box-title:link { FONT-WEIGHT: bold; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif; BACKGROUND-COLOR: #e6e6e2; = TEXT-DECORATION: none } A.box-title:active { FONT-WEIGHT: bold; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif; BACKGROUND-COLOR: #e6e6e2; = TEXT-DECORATION: none } A.box-title:visited { FONT-WEIGHT: bold; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif; BACKGROUND-COLOR: #e6e6e2; = TEXT-DECORATION: none } A.box-title:hover { FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; = TEXT-DECORATION: underline } .leftnav-shaded-box { BORDER-RIGHT: #bdbdbd 1px solid; PADDING-RIGHT: 0px; BORDER-TOP: = #bdbdbd 1px solid; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px = 0px 6px; BORDER-LEFT: #bdbdbd 1px solid; PADDING-TOP: 0px; = BORDER-BOTTOM: #bdbdbd 1px solid; LIST-STYLE-TYPE: none } .leftnav-shaded-box H1 { PADDING-RIGHT: 7px; PADDING-LEFT: 7px; FONT-WEIGHT: bold; FONT-SIZE: = 12px; PADDING-BOTTOM: 3px; MARGIN: 0px; COLOR: #000000; LINE-HEIGHT: = 13px; PADDING-TOP: 3px; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", = Tahoma, sans-serif; BACKGROUND-COLOR: #dadada } .leftnav-shaded-box UL { BORDER-RIGHT: 0px; BORDER-TOP: 0px; MARGIN: 0px; BORDER-LEFT: 0px; = BORDER-BOTTOM: 0px; LIST-STYLE-TYPE: none } .leftnav-shaded-box UL LI { PADDING-RIGHT: 5px; BORDER-TOP: #bdbdbd 1px solid; DISPLAY: block; = PADDING-LEFT: 18px; BACKGROUND: url(/images/left-nav-red-arrow.gif) = #eaebe6 no-repeat 7px 10px; LIST-STYLE-IMAGE: url(/images/spacer.gif); = PADDING-BOTTOM: 5px; MARGIN: 0px; FONT: 12px Arial, Helvetica, = sans-serif; PADDING-TOP: 5px; LIST-STYLE-TYPE: none } .leftnav-shaded-box UL LI A:link { COLOR: #1a1a1a; TEXT-DECORATION: none } .leftnav-shaded-box UL LI A:visited { COLOR: #1a1a1a; TEXT-DECORATION: none } .leftnav-shaded-box UL LI A:active { COLOR: #1a1a1a; TEXT-DECORATION: none } .leftnav-shaded-box UL LI A:hover { TEXT-DECORATION: underline } .navigation-white { FONT-SIZE: 11px; COLOR: #fff } TD.navigation-white { FONT-SIZE: 11px; COLOR: #fff } A.navigation-white:link { FONT-SIZE: 11px; COLOR: #fff } A.navigation-white:visited { FONT-SIZE: 11px; COLOR: #fff } A.navigation-white:active { FONT-SIZE: 11px; COLOR: #fff } A.navigation-white:hover { COLOR: #f1efef } .navigation-gray { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray:visited { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray:active { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray-link { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray-link:visited { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray-link:active { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray-link:hover { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray:hover { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .navigation-selected { FONT-SIZE: 11px; COLOR: #999999; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .navigation-dark-gray { FONT-SIZE: 11px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-gray-link { FONT-SIZE: 11px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-gray-link:visited { FONT-SIZE: 11px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-gray-link:active { FONT-SIZE: 11px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .navigation-black { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-black-link { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-black-link:visited { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-black-link:active { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-black-link:hover { FONT-SIZE: 11px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-gray-link:hover { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .navigation-dark-red { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red:link { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red:active { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red:visited { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red-link { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red-link:visited { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red-link:active { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red-link:hover { FONT-SIZE: 11px; COLOR: #990000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red:hover { FONT-SIZE: 11px; COLOR: #990000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .red-header { FONT-WEIGHT: bold; FONT-SIZE: 13px; COLOR: #cc0000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } A.red-header { FONT-WEIGHT: bold; FONT-SIZE: 13px; COLOR: #cc0000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } A.red-header:visited { FONT-WEIGHT: bold; FONT-SIZE: 13px; COLOR: #cc0000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } A.red-header:active { FONT-WEIGHT: bold; FONT-SIZE: 13px; COLOR: #cc0000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } A.red-header:hover { FONT-WEIGHT: bold; FONT-SIZE: 13px; COLOR: #990000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } .dark-red { COLOR: #993300; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } A.dark-red-link { COLOR: #993300; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } A.dark-red-link:visited { COLOR: #993300; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } A.dark-red-link:active { COLOR: #993300; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } A.dark-red-link:hover { FONT-SIZE: 11px; COLOR: #990000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .black-text { FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.black-text { FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.black-text:visited { FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.black-text:active { FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .black-text-b { FONT-WEIGHT: bold; FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } A.black-text:hover { FONT-SIZE: 12px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .quote { FONT-WEIGHT: bold; FONT-SIZE: 12px; COLOR: #996666; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } .caption { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .caption-image { BORDER-RIGHT: #bdbdbd 0px solid; BORDER-TOP: #bdbdbd 0px solid; = BORDER-LEFT: #bdbdbd 0px solid; BORDER-BOTTOM: #bdbdbd 1px solid } .dates { FONT-SIZE: 11px; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } .protocol-date-label { FONT-WEIGHT: bold; FONT-SIZE: 11px; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .protocol-dates { FONT-SIZE: 11px; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } SUP.header { FONT-SIZE: 13px; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } .dictionary-alpha-list { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px } A.dictionary-alpha-list { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px } A.dictionary-alpha-list:link { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px } A.dictionary-alpha-list:active { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px } A.dictionary-alpha-list:visited { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px } A.dictionary-alpha-list:hover { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px; BACKGROUND-COLOR: #ffffff } .dictionary-partial-match { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match:link { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match:active { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match:visited { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match:hover { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } .dictionary-partial-match-n { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match-n { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match-n:link { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match-n:active { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match-n:visited { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match-n:hover { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .search-result { FONT-WEIGHT: bold; FONT-SIZE: 17px; COLOR: #646464; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } .content-gray-background { PADDING-RIGHT: 12px; PADDING-LEFT: 12px; BACKGROUND: #f5f5f3; = PADDING-BOTTOM: 20px; PADDING-TOP: 14px } .pdq-shaded-area { PADDING-RIGHT: 12px; PADDING-LEFT: 12px; BACKGROUND: #f5f5f3; = PADDING-BOTTOM: 20px; PADDING-TOP: 14px } .note { PADDING-RIGHT: 0px; BORDER-TOP: #d3d3d3 1px solid; PADDING-LEFT: 0px; = PADDING-BOTTOM: 18px; PADDING-TOP: 18px; BORDER-BOTTOM: #d3d3d3 1px = solid } .druginfosummarybox { BORDER-RIGHT: #c9cace 1px solid; PADDING-RIGHT: 16px; BORDER-TOP: = #c9cace 1px solid; PADDING-LEFT: 16px; PADDING-BOTTOM: 16px; MARGIN: = 0px; BORDER-LEFT: #c9cace 1px solid; WIDTH: 516px; PADDING-TOP: 16px; = BORDER-BOTTOM: #c9cace 1px solid; BACKGROUND-COLOR: #eff2f7; = voice-family: inherit } .Protocol-Title { FONT-WEIGHT: bold; FONT-SIZE: 17px; COLOR: #000000 } .Protocol-OfficialTitle { FONT-WEIGHT: bold; FONT-SIZE: 16px; COLOR: #000000; LINE-HEIGHT: 18px } A.Protocol-TOC-Link { COLOR: #9c3303 } A.Protocol-TOC-Link:visited { COLOR: #9c3303 } A.Protocol-TOC-Link:active { COLOR: #9c3303 } A.Protocol-TOC-Link:hover { COLOR: #990000; TEXT-DECORATION: underline } .Protocol-TOC-SubLink { TEXT-DECORATION: none } .Protocol-Section-Heading { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #000000 } .Protocol-Section-SubHeading { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #000000 } .Protocol-PublishedResults-PUBMED { FONT-SIZE: 10px } .Protocol-DownloadDate { FONT-WEIGHT: bold } .Protocol-BasicStudy-Grayborder { BACKGROUND-COLOR: #bdbdbd } .Protocol-LeadOrg-OrgName { FONT-WEIGHT: bold } .Protocol-BasicStudy-TD-Grayborder { BACKGROUND-COLOR: #bdbdbd } .Protocol-BasicStudy-Heading { FONT-WEIGHT: bold } .Protocol-BasicStudy-PrimaryID { FONT-WEIGHT: bold } .Protocol-BasicStudy-AlternateID { FONT-SIZE: 10px } .Protocol-Term-SubHeading { FONT-WEIGHT: bold } .Protocol-Term-Table-Heading { FONT-WEIGHT: bold } .Protocol-EntryCriteria-DiseaseCharacteristics { FONT-WEIGHT: bold } .Protocol-EntryCriteria-PatientCharacteristics { FONT-WEIGHT: bold } .Protocol-EntryCriteria-PriorConcurrentTherapy { FONT-WEIGHT: bold } .Protocol-EntryCriteria-GeneralEligibilityCriteria { FONT-WEIGHT: bold } .Protocol-Outcomes-Primary { FONT-WEIGHT: bold; FONT-STYLE: italic } .Protocol-country { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #000000; LINE-HEIGHT: 18px; = BACKGROUND-COLOR: #e6e6e2 } .Protocol-Site-CountryName { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #000000; LINE-HEIGHT: 18px; = BACKGROUND-COLOR: #e6e6e2 } .Protocol-Site-Country { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #000000; LINE-HEIGHT: 18px; = BACKGROUND-COLOR: #e6e6e2 } .Protocol-state { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #993333 } .Protocol-Site-StateName { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #993333 } .Protocol-Site-State { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #993333 } .Protocol-city { FONT-WEIGHT: bold } Protocol-Site-City { FONT-WEIGHT: bold } .Protocol-Site-SiteName { FONT-WEIGHT: bold; FONT-STYLE: italic } .Protocol-Purpose { FONT-WEIGHT: bold } .Protocol-EligibilityText { FONT-WEIGHT: bold } .Protocol-TreatmentIntervention { FONT-WEIGHT: bold } .Protocol-PatientDisclaimer { FONT-WEIGHT: bold } .Protocol-LI-Title { FONT-WEIGHT: bold; FONT-STYLE: italic } .Protocol-IL-Title { FONT-WEIGHT: bold; FONT-STYLE: italic } .protocol-primaryprotocolid { FONT-WEIGHT: bold } .Protocol-OL-Title { FONT-WEIGHT: bold; FONT-STYLE: italic } LI.Protocol-LI { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: disc } LI.Protocol-IL-Bullet { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: disc } LI.Protocol-IL-Dash { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: square } LI.Protocol-IL-Circle { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: none } LI.Protocol-IL-Simple { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: none } LI.Protocol-OL-Lroman { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: lower-roman } LI.Protocol-OL-Uroman { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: upper-roman } LI.Protocol-OL-Lalpha { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: lower-alpha } LI.Protocol-OL-Ualpha { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: upper-alpha } LI.Protocol-OL-Arabic { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: decimal } OL.Protocol-KeyPoints-Bullet { LIST-STYLE-TYPE: disc } OL.Protocol-KeyPoints-Dash { LIST-STYLE-TYPE: square } LI.CDR { MARGIN-TOP: 5px; PADDING-LEFT: 5px; FONT-SIZE: 13px; LIST-STYLE-IMAGE: = none; MARGIN-BOTTOM: 0px; MARGIN-LEFT: 0px; LINE-HEIGHT: 16px } .Protocol-ScientificName { FONT-STYLE: italic } 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.footer-text { FONT-SIZE: 11px; COLOR: #666666; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.footer-link:hover { FONT-SIZE: 11px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .search-field { WIDTH: 120px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, "Trebuchet = MS", Tahoma, sans-serif; HEIGHT: 22px } .leftnav { FONT-SIZE: 11px; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } .box-title { FONT-WEIGHT: bold; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif; BACKGROUND-COLOR: #e6e6e2; = TEXT-DECORATION: none } A.box-title { FONT-WEIGHT: bold; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif; BACKGROUND-COLOR: #e6e6e2; = TEXT-DECORATION: none } A.box-title:link { FONT-WEIGHT: bold; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif; BACKGROUND-COLOR: #e6e6e2; = TEXT-DECORATION: none } A.box-title:active { FONT-WEIGHT: bold; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif; BACKGROUND-COLOR: #e6e6e2; = TEXT-DECORATION: none } A.box-title:visited { FONT-WEIGHT: bold; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif; BACKGROUND-COLOR: #e6e6e2; = TEXT-DECORATION: none } A.box-title:hover { FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; = TEXT-DECORATION: underline } .leftnav-shaded-box { BORDER-RIGHT: #bdbdbd 1px solid; PADDING-RIGHT: 0px; BORDER-TOP: = #bdbdbd 1px solid; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px = 0px 6px; BORDER-LEFT: #bdbdbd 1px solid; PADDING-TOP: 0px; = BORDER-BOTTOM: #bdbdbd 1px solid; LIST-STYLE-TYPE: none } .leftnav-shaded-box H1 { PADDING-RIGHT: 7px; PADDING-LEFT: 7px; FONT-WEIGHT: bold; FONT-SIZE: = 12px; PADDING-BOTTOM: 3px; MARGIN: 0px; COLOR: #000000; LINE-HEIGHT: = 13px; PADDING-TOP: 3px; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", = Tahoma, sans-serif; BACKGROUND-COLOR: #dadada } .leftnav-shaded-box UL { BORDER-RIGHT: 0px; BORDER-TOP: 0px; MARGIN: 0px; BORDER-LEFT: 0px; = BORDER-BOTTOM: 0px; LIST-STYLE-TYPE: none } .leftnav-shaded-box UL LI { PADDING-RIGHT: 5px; BORDER-TOP: #bdbdbd 1px solid; DISPLAY: block; = PADDING-LEFT: 18px; BACKGROUND: url(/images/left-nav-red-arrow.gif) = #eaebe6 no-repeat 7px 10px; LIST-STYLE-IMAGE: url(/images/spacer.gif); = PADDING-BOTTOM: 5px; MARGIN: 0px; FONT: 12px Arial, Helvetica, = sans-serif; PADDING-TOP: 5px; LIST-STYLE-TYPE: none } .leftnav-shaded-box UL LI A:link { COLOR: #1a1a1a; TEXT-DECORATION: none } .leftnav-shaded-box UL LI A:visited { COLOR: #1a1a1a; TEXT-DECORATION: none } .leftnav-shaded-box UL LI A:active { COLOR: #1a1a1a; TEXT-DECORATION: none } .leftnav-shaded-box UL LI A:hover { TEXT-DECORATION: underline } .navigation-white { FONT-SIZE: 11px; COLOR: #fff } TD.navigation-white { FONT-SIZE: 11px; COLOR: #fff } A.navigation-white:link { FONT-SIZE: 11px; COLOR: #fff } A.navigation-white:visited { FONT-SIZE: 11px; COLOR: #fff } A.navigation-white:active { FONT-SIZE: 11px; COLOR: #fff } A.navigation-white:hover { COLOR: #f1efef } .navigation-gray { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray:visited { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray:active { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray-link { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray-link:visited { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray-link:active { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray-link:hover { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-gray:hover { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .navigation-selected { FONT-SIZE: 11px; COLOR: #999999; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .navigation-dark-gray { FONT-SIZE: 11px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-gray-link { FONT-SIZE: 11px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-gray-link:visited { FONT-SIZE: 11px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-gray-link:active { FONT-SIZE: 11px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .navigation-black { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-black-link { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-black-link:visited { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-black-link:active { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-black-link:hover { FONT-SIZE: 11px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-gray-link:hover { FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .navigation-dark-red { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red:link { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red:active { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red:visited { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red-link { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red-link:visited { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red-link:active { FONT-SIZE: 11px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red-link:hover { FONT-SIZE: 11px; COLOR: #990000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.navigation-dark-red:hover { FONT-SIZE: 11px; COLOR: #990000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .red-header { FONT-WEIGHT: bold; FONT-SIZE: 13px; COLOR: #cc0000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } A.red-header { FONT-WEIGHT: bold; FONT-SIZE: 13px; COLOR: #cc0000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } A.red-header:visited { FONT-WEIGHT: bold; FONT-SIZE: 13px; COLOR: #cc0000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } A.red-header:active { FONT-WEIGHT: bold; FONT-SIZE: 13px; COLOR: #cc0000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } A.red-header:hover { FONT-WEIGHT: bold; FONT-SIZE: 13px; COLOR: #990000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } .dark-red { COLOR: #993300; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } A.dark-red-link { COLOR: #993300; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } A.dark-red-link:visited { COLOR: #993300; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } A.dark-red-link:active { COLOR: #993300; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } A.dark-red-link:hover { FONT-SIZE: 11px; COLOR: #990000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .black-text { FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.black-text { FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.black-text:visited { FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.black-text:active { FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .black-text-b { FONT-WEIGHT: bold; FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } A.black-text:hover { FONT-SIZE: 12px; COLOR: #333333; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .quote { FONT-WEIGHT: bold; FONT-SIZE: 12px; COLOR: #996666; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } .caption { FONT-SIZE: 11px; COLOR: #4d4d4d; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .caption-image { BORDER-RIGHT: #bdbdbd 0px solid; BORDER-TOP: #bdbdbd 0px solid; = BORDER-LEFT: #bdbdbd 0px solid; BORDER-BOTTOM: #bdbdbd 1px solid } .dates { FONT-SIZE: 11px; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } .protocol-date-label { FONT-WEIGHT: bold; FONT-SIZE: 11px; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .protocol-dates { FONT-SIZE: 11px; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } SUP.header { FONT-SIZE: 13px; FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, = sans-serif } .dictionary-alpha-list { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px } A.dictionary-alpha-list { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px } A.dictionary-alpha-list:link { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px } A.dictionary-alpha-list:active { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px } A.dictionary-alpha-list:visited { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px } A.dictionary-alpha-list:hover { PADDING-RIGHT: 4px; PADDING-LEFT: 4px; FONT-SIZE: 11px; PADDING-BOTTOM: = 6px; VERTICAL-ALIGN: middle; COLOR: #a90101; PADDING-TOP: 6px; = FONT-FAMILY: Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif; HEIGHT: = 16px; BACKGROUND-COLOR: #ffffff } .dictionary-partial-match { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match:link { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match:active { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match:visited { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match:hover { FONT-WEIGHT: bold; FONT-SIZE: 12px; BACKGROUND-IMAGE: = url(/images/dictionary-ext-mtc-bg.gif); COLOR: #993300; FONT-FAMILY: = Arial, Verdana, "Trebuchet MS", Tahoma, sans-serif } .dictionary-partial-match-n { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match-n { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match-n:link { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match-n:active { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match-n:visited { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } A.dictionary-partial-match-n:hover { FONT-SIZE: 12px; COLOR: #993300; FONT-FAMILY: Arial, Verdana, = "Trebuchet MS", Tahoma, sans-serif } .search-result { FONT-WEIGHT: bold; FONT-SIZE: 17px; COLOR: #646464; FONT-FAMILY: Arial, = Verdana, "Trebuchet MS", Tahoma, sans-serif } .content-gray-background { PADDING-RIGHT: 12px; PADDING-LEFT: 12px; BACKGROUND: #f5f5f3; = PADDING-BOTTOM: 20px; PADDING-TOP: 14px } .pdq-shaded-area { PADDING-RIGHT: 12px; PADDING-LEFT: 12px; BACKGROUND: #f5f5f3; = PADDING-BOTTOM: 20px; PADDING-TOP: 14px } .note { PADDING-RIGHT: 0px; BORDER-TOP: #d3d3d3 1px solid; PADDING-LEFT: 0px; = PADDING-BOTTOM: 18px; PADDING-TOP: 18px; BORDER-BOTTOM: #d3d3d3 1px = solid } .druginfosummarybox { BORDER-RIGHT: #c9cace 1px solid; PADDING-RIGHT: 16px; BORDER-TOP: = #c9cace 1px solid; PADDING-LEFT: 16px; PADDING-BOTTOM: 16px; MARGIN: = 0px; BORDER-LEFT: #c9cace 1px solid; WIDTH: 516px; PADDING-TOP: 16px; = BORDER-BOTTOM: #c9cace 1px solid; BACKGROUND-COLOR: #eff2f7; = voice-family: inherit } .Protocol-Title { FONT-WEIGHT: bold; FONT-SIZE: 17px; COLOR: #000000 } .Protocol-OfficialTitle { FONT-WEIGHT: bold; FONT-SIZE: 16px; COLOR: #000000; LINE-HEIGHT: 18px } A.Protocol-TOC-Link { COLOR: #9c3303 } A.Protocol-TOC-Link:visited { COLOR: #9c3303 } A.Protocol-TOC-Link:active { COLOR: #9c3303 } A.Protocol-TOC-Link:hover { COLOR: #990000; TEXT-DECORATION: underline } .Protocol-TOC-SubLink { TEXT-DECORATION: none } .Protocol-Section-Heading { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #000000 } .Protocol-Section-SubHeading { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #000000 } .Protocol-PublishedResults-PUBMED { FONT-SIZE: 10px } .Protocol-DownloadDate { FONT-WEIGHT: bold } .Protocol-BasicStudy-Grayborder { BACKGROUND-COLOR: #bdbdbd } .Protocol-LeadOrg-OrgName { FONT-WEIGHT: bold } .Protocol-BasicStudy-TD-Grayborder { BACKGROUND-COLOR: #bdbdbd } .Protocol-BasicStudy-Heading { FONT-WEIGHT: bold } .Protocol-BasicStudy-PrimaryID { FONT-WEIGHT: bold } .Protocol-BasicStudy-AlternateID { FONT-SIZE: 10px } .Protocol-Term-SubHeading { FONT-WEIGHT: bold } .Protocol-Term-Table-Heading { FONT-WEIGHT: bold } .Protocol-EntryCriteria-DiseaseCharacteristics { FONT-WEIGHT: bold } .Protocol-EntryCriteria-PatientCharacteristics { FONT-WEIGHT: bold } .Protocol-EntryCriteria-PriorConcurrentTherapy { FONT-WEIGHT: bold } .Protocol-EntryCriteria-GeneralEligibilityCriteria { FONT-WEIGHT: bold } .Protocol-Outcomes-Primary { FONT-WEIGHT: bold; FONT-STYLE: italic } .Protocol-country { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #000000; LINE-HEIGHT: 18px; = BACKGROUND-COLOR: #e6e6e2 } .Protocol-Site-CountryName { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #000000; LINE-HEIGHT: 18px; = BACKGROUND-COLOR: #e6e6e2 } .Protocol-Site-Country { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #000000; LINE-HEIGHT: 18px; = BACKGROUND-COLOR: #e6e6e2 } .Protocol-state { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #993333 } .Protocol-Site-StateName { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #993333 } .Protocol-Site-State { FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #993333 } .Protocol-city { FONT-WEIGHT: bold } Protocol-Site-City { FONT-WEIGHT: bold } .Protocol-Site-SiteName { FONT-WEIGHT: bold; FONT-STYLE: italic } .Protocol-Purpose { FONT-WEIGHT: bold } .Protocol-EligibilityText { FONT-WEIGHT: bold } .Protocol-TreatmentIntervention { FONT-WEIGHT: bold } .Protocol-PatientDisclaimer { FONT-WEIGHT: bold } .Protocol-LI-Title { FONT-WEIGHT: bold; FONT-STYLE: italic } .Protocol-IL-Title { FONT-WEIGHT: bold; FONT-STYLE: italic } .protocol-primaryprotocolid { FONT-WEIGHT: bold } .Protocol-OL-Title { FONT-WEIGHT: bold; FONT-STYLE: italic } LI.Protocol-LI { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: disc } LI.Protocol-IL-Bullet { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: disc } LI.Protocol-IL-Dash { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: square } LI.Protocol-IL-Circle { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: none } LI.Protocol-IL-Simple { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: none } LI.Protocol-OL-Lroman { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: lower-roman } LI.Protocol-OL-Uroman { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: upper-roman } LI.Protocol-OL-Lalpha { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: lower-alpha } LI.Protocol-OL-Ualpha { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: upper-alpha } LI.Protocol-OL-Arabic { LIST-STYLE-IMAGE: none; LIST-STYLE-TYPE: decimal } OL.Protocol-KeyPoints-Bullet { LIST-STYLE-TYPE: disc } OL.Protocol-KeyPoints-Dash { LIST-STYLE-TYPE: square } LI.CDR { MARGIN-TOP: 5px; PADDING-LEFT: 5px; FONT-SIZE: 13px; 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