text:
This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
Cancer patients often have comorbid medical problems in addition to their underlying malignant disorders. In fact, patients older than 65 years bear a disproportionate burden of cancer as well as increased prevalence of medical problems such as chronic obstructive pulmonary disease, heart disease, diabetes, and hypertension.[1] Whether patients are seen in primary care or cancer care settings, unexplained symptoms often frustrate physicians and patients.[2] Because many advanced cancers spread to the thorax, symptoms such as dyspnea, cough, chest pain, or palpitations often present a challenge in sorting out the likely cause of the problem and developing appropriate interventions. Evidence-based recommendations have been published describing various approaches to the problems of cancer-related fatigue, anorexia, depression, and dyspnea.[3] Cancer patients are often also at higher risk for pulmonary infections.
Clinicians caring for cancer patients should be familiar with the assessment and treatment of common conditions that manifest as chest symptoms. In addition, it is important that these clinicians be familiar with some cancer-specific aspects of chest symptoms and syndromes. Dyspnea is a common symptom of certain cancers such as lung cancer and is also common in patients with numerous advanced cancers. It is often multifactorial. Optimal treatment requires an understanding of contributing etiologies and pathophysiologies in order to direct therapeutic interventions as clinically appropriate. Important cardiopulmonary syndromes include malignant pleural effusion, malignant pericardial effusion, superior vena cava syndrome, and lymphangitic carcinomatosis.
In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.
Dyspnea is defined as an uncomfortable awareness of breathing. It is a subjective experience involving many factors that modulate the quality and intensity of its perception. Patients with comparable degrees of functional lung impairment and disease burden may describe varying intensities of dyspnea. Patients use a host of different words and phrases to describe the sensation of breathlessness. Terms such as tightness and suffocating are sometimes used.[1]
Reports on the frequency of dyspnea also vary, depending on the setting and the extent of disease.[2] In one study, 49% of a general cancer population reported breathlessness, and 20% rated their breathlessness as moderate to severe.[3] Patients with advanced cancer experience this symptom more frequently and more intensely than do patients with limited disease. One study found that 75 of 135 patients with advanced cancer reporting to an outpatient palliative care clinic were experiencing moderate-to-severe dyspnea.[4] Breathlessness was a complaint at presentation in 60% of 289 patients with lung cancer.[5] Results of a large study showed that 70% of patients suffered from dyspnea in the last 6 weeks of life.[6] About one third of patients who could report the intensity of their dyspnea rated it as moderate to severe. Another study revealed that half of patients with advanced cancer scored their dyspnea as moderate to severe.[7]
The pathophysiological mechanisms of breathlessness are numerous and complex.[8] Peripheral and central mechanisms as well as mechanical and chemical pathways are involved.
The direct causes of dyspnea in patients with advanced cancer are numerous; categorizing them can assist in the etiologic work-up. One approach is to divide direct causes into the following four groups:
One study found that in patients experiencing dyspnea from advanced cancer, a median of five different abnormalities could have contributed to their shortness of breath.[7] Spirometry was abnormal in 93% of 100 patients examined, with 5% having obstructive patterns, 41% restrictive patterns, and 47% mixed patterns; 49% of patients had lung cancer, 91% had abnormal chest radiographs, and 65% had parenchymal or pleural involvement. These results indicate that a subset of patients will experience shortness of breath without any apparent lung involvement. The potentially correctable causes of dyspnea included hypoxia (40%), anemia (20%), and bronchospasm (52%). No significant association between the type of respiratory impairment and the degree of dyspnea was found. Most of these patients were current or former smokers. Most patients also had a significant lowering of their maximum inspiratory pressures, suggesting severe respiratory muscle dysfunction. This finding was duplicated in another study.[4] Of patients admitted to hospice care, 34% had histories of cardiac disease and 24% had histories of respiratory disease.[6] Only 39% of terminally ill patients who reported dyspnea had lung or pleural involvement. The etiology of dyspnea could not be clearly identified in approximately one quarter of patients. Another study found that 49% of lung cancer patients presented with airflow obstruction.[7,9]
Respiratory muscle dysfunction is an underrecognized factor contributing to dyspnea. Causes of respiratory muscle dysfunction include neuromuscular disease, malnutrition, and deficiencies of potassium, magnesium, and inorganic phosphate.[10] Poor oxygenation, muscle fatigue, abnormal cortisol and catecholamine levels, and circulating cytokines are also implicated.
Although it is commonly believed that anxiety is associated with breathlessness, researchers found that anxiety and shortness of breath do not invariably go together.[7] One study demonstrated that the involvement of the lungs by cancer, anxiety, and poor maximal inspiratory pressures were correlates of the intensity of dyspnea in patients with advanced cancer.
The multidimensional nature of dyspnea must be noted in the complicated assessment of this symptom. Objective signs such as tachypnea or the use of accessory breathing muscles frequently do not match a patient's perception of dyspnea and the degree of functional impairment it causes. Numerous factors, including psychosocial issues, may affect a patient's experience of dyspnea. Pulmonary function tests, with few exceptions, play a limited role in the assessment of this syndrome. Lack of a clear understanding of the pathophysiological mechanisms underlying dyspnea hampers the clinician's overall ability to effectively manage it.[8,11]
There is no consensus on what constitutes the best instrument for assessing dyspnea. Visual analog and numerical rating scales appear to be useful and are commonly utilized.[8,11] The Borg Scale is occasionally utilized.[11] The Cancer Dyspnea Scale is a multidimensional instrument, initially developed in Japan for patients with lung cancer and later translated into Swedish. The scale has been shown to be valid and reliable in patients with advanced lung cancer. The subscales measure sense of effort (physical dimension), sense of anxiety (psychological dimension), and sense of discomfort.[12] These tools are limited, however, because they are unidimensional and do not account for the relative contribution of different factors to a patient's perception of breathlessness. Assessment should include the impact of dyspnea on the patient's functional status and appreciation of the dynamic component of dyspnea—namely, exertional dyspnea.
A comprehensive history and examination are essential to an accurate assessment of dyspnea.[8,11] The temporal onset, qualities of the symptom, associated symptoms, precipitating and relieving events or activities, and responses to medications should be reviewed. Sudden onset may herald a pulmonary embolism or infection, whereas gradual onset may suggest the development of a pleural effusion. A history of obstructive airways or cardiac disease can shed some light on possible underlying causes. Investigations such as measuring oxygen saturation can be useful in determining whether a patient is hypoxic. In the setting of advanced, incurable cancer, arterial blood gasses play a limited role.
Diagnostic tests that may help to determine the etiology of dyspnea include chest imaging by radiography, computer-assisted tomography, complete blood counts, oxygen saturation at rest and with exercise and, to a much lesser extent, pulmonary function tests. Maximal inspiratory pressure (MIP) measurements may be helpful, particularly if no apparent cause can be found.[7] MIP is a reliable functional test of the strength of the diaphragm and other respiratory muscles.
Management of Dyspnea and Coughing
Management of underlying causes
As with all symptoms, it is essential to identify and treat the underlying cause(s) of dyspnea if possible and when appropriate. Examples of specific underlying causes (some of them potentially reversible) and their treatments include the following:
Symptomatic management
Symptomatic management of dyspnea is based primarily on oxygen therapy, opioids for palliation of dyspnea, and treatment of underlying causes (e.g., superimposed infection) when appropriate.
Patients who are hypoxic on room air are likely to benefit from oxygen therapy, probably through a decrease in the chemoreceptor input to the respiratory center and the brain cortex. In two controlled trials, cancer patients with dyspnea who were randomized in a crossover design showed significant improvement in their dyspnea.[14,15][Level of evidence: I] The role of oxygen in the treatment of non–hypoxia-related dyspnea in cancer patients is less clear.
Opioids represent an extremely effective treatment for dyspnea in cancer patients. Fear of side effects should not prevent the appropriate use of opioids in this setting. Most authorities believe that, if used appropriately, opioids do not hasten death in dyspneic cancer patients; rather, they reduce physical and psychological distress and exhaustion, and early use improves quality of life.[11,16] Clinically significant hypoventilation following opioid therapy depends largely on the history of previous exposure to opioids and the rate of increase of the opioid dose. As with opioid use in pain management, the principles of starting at a regular low dose in opioid-naïve patients followed by appropriate dose titration applies. Opioid therapy for dyspnea is administered similarly to, and often concurrent with, opioid therapy for pain control. Most of the available evidence supports the role of opioids in relieving dyspnea in malignant and nonmalignant conditions.[17,18][Level of evidence: I];[19,20,21][Level of evidence: II]
Anecdotal and experimental evidence suggest a role for nebulized opioid administration in the treatment of dyspnea.[22,23,24] Opioid receptors are present on sensory nerve endings in the airways; however, nebulization is an inefficient way of administering drugs.[22] Pharmacokinetic studies suggest that the systemic bioavailability of nebulized morphine is extremely poor and erratic, varying from 4% to 8%.[25] Some patients may experience claustrophobia. Available evidence does not support the clinical use of nebulized opioids. More clinical trials are needed to better determine the role of this mode of treatment.
Other options suggested for symptomatic treatment include methylxanthines, sedatives, tranquilizers, nebulized local anesthetics, and antiprostaglandins. The role of methylxanthines in cancer-related dyspnea has not been clarified. Chlorpromazine and promethazine have been shown to decrease dyspnea without affecting ventilation in noncancer patients, but their role in cancer-related dyspnea is unclear. Four out of five randomized controlled trials failed to demonstrate any benefit for using benzodiazepines in cancer patients.[11];[26][Level of evidence: I] One randomized single-blind study suggests that the combination of two scheduled medications (subcutaneous morphine and subcutaneous midazolam) and one as needed (subcutaneous morphine) for episodes of breakthrough dyspnea is more effective than the other evaluated combinations for controlling breakthrough dyspnea and requires further study.[27][Level of evidence: I] The role of benzodiazepines appears to be limited to treatment of dyspnea that is considered a somatic manifestation of a panic disorder or use when a patient has concurrent severe anxiety. No evidence supports the use of nebulized local anesthetics for the treatment of breathlessness.
General support measures
In addition to adequate pharmacological therapies, a number of nonpharmacological measures are suggested. These include pursed-lip breathing, diaphragmatic breathing and muscle training, cold air directed across the cheek, meditation, relaxation training, biofeedback techniques, and psychotherapy. The effectiveness of these measures in relieving breathlessness appears to be variable.
Chronic cough
In some patients, chronic coughing may be the source of major suffering.[11] Chronic cough can cause pain, interfere with sleep, aggravate dyspnea, and worsen fatigue. The causes of cough can be classified much like the causes of dyspnea. The optimal therapy for chronic cough is treatment of the underlying disorder. Cough-suppressing agents such as opioids are commonly utilized. Anecdotal evidence suggests a role for inhaled local anesthetics, which should be utilized judiciously and sparingly; they are unpleasant to the taste and obtund the gag reflex, and anaphylactic reactions to preservatives in these solutions have been documented. Opioid and nonopioid antitussives such as dextromethorphan may act synergistically, but further studies are required to confirm this hypothesis.[11] In cases of increased sputum production, expectorants and mucolytics have been employed, but the effects have not been well evaluated. Inhaled sodium cromoglycate has shown promise as a safe method of controlling chronic coughing related to lung cancer.[26]
Current Clinical Trials
Check NCI's list of cancer clinical trials for U.S. supportive and palliative care trials about dyspnea that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Malignant pleural effusions are a common complication of malignancy, and malignancy is a common cause of pleural effusions in general. Malignancy accounts for roughly 40% of symptomatic pleural effusions, with congestive heart failure and infection being the other leading causes.[1] Lung cancer, breast cancer, lymphoma, and leukemia account for approximately 75% of all malignancy-associated effusions. Significant use of health care resources is attributable to malignant effusions, with approximately 100,000 cases per year being diagnosed in the United States and 43 cases being detected per 100,000 hospital admissions.[2]
The normal pleural fluid space is occupied with approximately 10 cc of fluid with 2 g/dL protein. A pleural effusion is an accumulation of an abnormal amount of fluid between the visceral and parietal pleura of the chest. Normally, pleural fluid is absorbed by pulmonary venous capillaries (80%–90%), with some of it also absorbed by pleural lymphatics. Malignant effusions are usually exudative rather than transudative. Exudative effusions exhibit any one of the following characteristics:[3]
These exudative malignant effusions are generally caused by pleural metastases, disruption of pulmonary capillary endothelium, or malignant obstruction of pleural lymphatics. Paramalignant effusions may result from chemotherapy, radiation therapy, atelectasis, and/or lymph node involvement.
Common symptoms associated with malignant pleural effusions include dyspnea, cough, and chest discomfort. About 20% of patients may experience weight loss and malaise. A chest x-ray is most commonly used for radiographic assessment. About 175 cc of pleural fluid will cause a blunted costophrenic angle discernible on chest radiography. A chest computerized tomography scan is more sensitive than a simple chest x-ray and is often used for assessment of loculated effusions because, in some instances, up to 500 cc of loculated fluid can be obscured behind the dome of the diaphragm.[1]
Not all pleural effusions detected in cancer patients will turn out to be malignant effusions. Cancer patients are prone to developing conditions such as congestive heart failure, pneumonia, pulmonary embolism, malnutrition, and associated low serum albumin, each of which may cause a symptomatic effusion for which the clinical management would substantially differ from the management of a malignant effusion. For this reason, cytologic assessment is important. Pleural fluid cytology requires a minimum sample of 250 cc. The morphology of cells obtained from the pleural space can be difficult to assess because of mesothelial and macrophage abnormalities. The diagnostic sensitivity of pleural fluid cytology is approximately 65%, with a specificity of 97%.[1] Flow cytometry can be applied to these specimens and is often useful, especially for assessment of lymphomas. Thoracoscopy and pleural biopsy are rarely needed for definitive diagnosis, but these techniques may be useful when routine pleural fluid collection and assessment are difficult because of loculation of the effusion. Thoracoscopy-guided biopsy is generally performed under local anesthesia and has a yield of more than 80%, with a lower risk of complications than thoracotomy.
Management of Malignant Pleural Effusions
To treat or not to treat
Pleural effusions are generally markers of advanced, unresectable disease or disease progression. The median survival for patients with malignant pleural effusions is around 3 to 4 months.[4,5] Because a paramalignant effusion due to pneumonia or atelectasis may be present, the cytology should be confirmed before major treatment decisions are made. Once the cytology has been confirmed, the management strategy depends on the underlying primary malignancy and the number and type of previous therapies. For example, patients with newly diagnosed small cell carcinoma or malignant lymphoma are very likely to respond to systemic chemotherapy; however, patients who have already failed several lines of chemotherapy for gastric or ovarian cancer are unlikely to obtain significant palliation with systemic therapy.
About three-quarters of patients exhibit symptoms such as cough, dyspnea, and/or chest discomfort. Such patients may benefit from efforts to reduce the fluid burden, depending on their performance status, expected survival, and preference for risks versus benefits. The literature on the efficacy of treatment for pleural effusions is difficult to interpret because of the paucity of randomized trials and the wide variability in the response criteria and the timing and duration of follow-up in uncontrolled trials.[6,7] Generally, the goal of therapy is palliation of symptoms. Measures of success may include complete drainage of the effusion, lung re-expansion, lack of fluid reaccumulation (i.e., duration of response), and subjective report of symptom relief. The choice of treatment depends on patient prognosis, functional status, and goals of care.
Thoracentesis involves percutaneous insertion of a needle for drainage of the effusion. Thoracentesis is not expected to permanently resolve the problem, but rather to alleviate symptoms that are acute and severe. The use of thoracentesis is also appropriate as a therapeutic trial to determine whether fluid drainage is beneficial when the relationship between symptoms and effusion is unclear. Tunneled pleural catheters allow up to 96% of patients to achieve symptom improvement, with spontaneous pleurodesis occurring on its own in up to 44% of patients.[8]
Most effusions will reaccumulate a few days after thoracentesis. Reaccumulation rate is approximately 98% by day 30.[9] Repeated thoracenteses carry the potential risks of bleeding, infection, and pneumothorax. Other potential complications of thoracentesis include noncardiogenic pulmonary edema from rapid lung re-expansion (usually with the rapid removal of >1,500 cc) and pleural shock caused by an excessive vagal response to penetration of the parietal pleura. Any of these complications may be lethal, especially for the cancer patient with poor cardiopulmonary reserve.
Use of pleural sclerosing agents after chest tube drainage
Chemical sclerosants may be administered through a chest tube to create inflammation and subsequent fusion of the parietal and visceral pleura so that fluid cannot reaccumulate in this potential space. This kind of fusion is called pleurodesis. Numerous chemical agents can cause the irritation necessary to produce pleurodesis. The ideal agent would produce effective pleurodesis with minimal cost and minimal side effects. Agents that have been studied include chemotherapeutic agents (bleomycin, cisplatin, etoposide, doxorubicin, mitomycin-C, fluorouracil), antibiotics (doxycycline, minocycline, tetracycline), infectious agents (Corynebacterium parvum), biological agents (interferon beta, interleukin-2), bovine dermal collagen,[10][Level of evidence: II] and other agents (talc, methylprednisolone). Several uncontrolled trials and case series report the efficacy of pleurodesis,[11];[12,13][Level of evidence: II];[14,15] as do numerous randomized trials.[16,17,18,19,20,21,22][Level of evidence: I] A meta-analysis of pleurodesis studies reported between 1966 and 1992 indicates that about two thirds of patients respond to pleurodesis and that tetracyclines (or tetracycline replacement agents such as doxycycline and minocycline), bleomycin, and talc appear to be the most effective agents.[23] A prospective randomized study of video-assisted thoracoscopic pleurodesis with talc versus doxycycline in 33 patients with malignant pleural effusion suggests that talc provides superior short-term and long-term results.[24][Level of evidence: I] Talc appears to be the least expensive agent, at least when given as a slurry rather than by video-assisted thoracoscopic talc insufflation.[22][Level of evidence: I] Bleomycin, however, is the only agent approved by the Food and Drug Administration for the prevention of recurrent pleural effusions.[1] An observational cohort study investigated the use of intrapleural urokinase in 48 patients with loculated pleural effusions or trapped lungs. Lung reexpansion and resolution of dyspnea occurred in approximately 60% of patients, suggesting that intrapleural urokinase may be useful in treating loculated pleural effusions or trapped lungs in medically inoperable cancer patients. Most responders successfully maintained pleurodesis when urokinase was followed by minocycline pleurodesis.[25][Level of evidence: II]
Surgical treatment
For rare patients, standard management of the malignant effusion is unsuccessful and aggressive treatment remains appropriate. Pleuroperitoneal shunting can be considered for these patients. This procedure involves implantation of a shunt with one-way valves that allow the transfer of fluid from the pleural space to the peritoneal space, in which the fluid creates less hazard and is more easily removed. Another option is surgical pleurectomy, but this procedure requires general anesthesia. The risks of significant acute and chronic pain as well as other morbidity approaches 20% to 25%, and the risk of 1-month mortality is 5% to 10%.[2]
Check NCI's list of cancer clinical trials for U.S. supportive and palliative care trials about malignant pleural effusion that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.
Malignant pericardial effusions occur in up to 21% of cancer patients [1,2,3] and are frequently not suspected until clinical signs or symptoms of pericardial tamponade develop.[4] Two thirds of patients have subclinical pericardial effusions with no overt cardiovascular signs or symptoms.[5,6] One half of cases of pericardial effusion initially present with symptoms of cardiac tamponade.[7] In one half of cases, pericardial effusion is the first sign of malignant disease.[8] Symptoms of pericardial effusion are often attributed to the underlying cancer. Dyspnea, fatigue, or asthenia may be the initial symptoms.[9] Symptomatic pericardial effusions are often a preterminal event; however, significant symptom palliation can be achieved by prompt diagnosis and management.
Of patients with malignant pericardial effusions, 50% will have concomitant pleural effusions, and one third will have pulmonary parenchymal disease.[4]
One third of patients with pericardial metastases will eventually die from pericardial tamponade.[4] Pericardial involvement contributed to the cause of death in 85% of patients in a series reported in 1962 but in only 46% of patients in a recent study.[10] Improvements in diagnostic and therapeutic options account for the decrease in mortality over the past 40 years.
Incidence and Prevalence
Malignant pericardial effusion occurs in up to 21% of autopsy series in patients with common malignancies.[4,7] Of patients with lung cancer, 33% have pericardial metastases at autopsy, and one third of cases of pericardial metastases are caused by lung cancer. Breast cancer causes 25% of pericardial effusions, and about 25% of patients with breast cancer have pericardial effusion. Hematological malignancies (leukemia, Hodgkin disease, non-Hodgkin lymphoma) cause 15% of cases of malignant pericardial effusions.[11]
A retrospective review of 23,592 effusions over a 24-year period revealed 65 malignant effusions (17%) out of 375 pericardial effusions. Lung cancer was the most common cancer found among the malignant pericardial effusions in males, and breast cancer was the most common in females. In 43% of cases, pericardial effusion was the first detected sign of cancer. Of patients diagnosed with malignant pericardial effusions, 86% died within 1 year of diagnosis, with nearly one third dying within the first month.[8]
In a study of 31 patients with both cancer and pericardial effusions, malignant pericardial effusion accounted for 58% of the effusions, 32% were caused by benign idiopathic pericarditis, and radiation pericarditis caused 10% of cases.[11,12]
Malignant involvement of the pericardium is the most common reason for development of pericardial effusions, which result from blockage of venous and lymphatic circulation of pericardial fluid. Such blockage may be caused by primary malignancy of the pericardium, as with pericardial mesothelioma, or by tumors arising in the myocardium, including angiosarcoma, rhabdomyosarcoma, and malignant fibrous histiocytosis. Malignancies can also involve the pericardium through direct extension from carcinomas of the lung or esophagus, thymoma, or lymphoma.[9] Lymphatic or hematogenous metastasis to the pericardium occurs most commonly with carcinomas of the breast and lung, leukemia, lymphoma, and melanoma. Primary tumors of the pleura or pericardium have recently been termed primary intrathoracic malignant effusions.[13]
Nonmalignant causes of pericardial effusion include pericarditis, myocardial infarction, uremia, hypothyroidism, systemic lupus erythematosus, trauma, postsurgical pericardotomy syndrome, and intrapericardial hematomas.[14,15,16] AIDS may also cause pericardial effusion with pericarditis.[17] Radiation therapy or chemotherapy drugs can cause pericarditis without metastatic involvement of the pericardium. Radiation pericarditis is usually associated with radiation doses to the cardiac window exceeding 3,000 cGy [10] and occurs most frequently in patients who have received mediastinal radiation for Hodgkin disease or breast cancer.[10] Doxorubicin and cyclophosphamide have been associated with the development of acute pericarditis with effusions.[11,12] Other drugs that may cause acute pericarditis include procainamide, hydralazine, isoniazid, methysergide, phenytoin, and anticoagulants.
Pericardial tamponade results from progressive fluid accumulation in the pericardial sac, causing elevated intrapericardial pressure, diminished stroke volume, decreased cardiac output, progressive decrease in cardiac diastolic filling, and hemodynamic compromise resulting in death if not treated. Hemodynamic compromise occurs when the normal amount of pericardial fluid (approximately 15–50 cc) increases to 200 cc to 1,800 cc.[15,18] When fluid accumulates rapidly, as little as 250 cc of fluid can result in tamponade.[11,19]
Dyspnea occurs in 93% of patients with pericardial effusions.[6] Cough, chest pain, and orthopnea (discomfort with breathing while lying flat) are common symptoms. Other symptoms of pericardial effusion include upper abdominal distention or pressure due to downward hepatic distention, hiccups due to pressure on the diaphragm, or pleuritic pain due to stretching of the pericardium (especially when lying flat). Signs of effusion include Kussmaul's sign (increased distention of jugular veins with inspiration), Freidreich's sign (rapid diastolic descent of the venous pulse), and pulsus paradoxus (decrease of more than 10 mm Hg in the diastolic pressure on inspiration). Pericardial friction rubs and fever are more commonly associated with nonmalignant causes of pericardial effusions than malignant etiologies.[9]
Signs of pericardial tamponade include tachycardia, pulsus paradoxus, elevated jugular venous pressure, and hypotension; however, some patients may develop tamponade without this clinical pattern.[4]
Chest radiography may show widening of the cardiac silhouette [7] if the amount of pericardial fluid collection exceeds 250 cc.[20] Chest x-ray cannot determine the degree of cardiac dysfunction or tamponade. Loculated pericardial effusions may not be apparent on standard posterior/anterior or lateral chest radiographic views.[15]
Transthoracic echocardiography using apical, subxiphoid, and parasternal views can evaluate the presence, quantity, and quality of suspected pericardial effusions as well as associated pericardial masses and inflammation. Moderate effusions on echocardiography show an echo-free space of 10 mm to 20 mm during diastole in M-mode or 2-dimensional echocardiography, whereas severe effusions have an echo-free space exceeding 20 mm.[21,22] Echocardiography can also determine right and left ventricular function and the possibility of right ventricular or atrial diastolic collapse.[7] Left ventricular collapse due to large pleural effusion without clinically significant pericardial effusions has been reported;[4,16,23,24] however, transesophageal echocardiography may be useful for loculated effusions due to adhesions adjacent to the atria, where the thinness of the atrial wall may not be well visualized on transthoracic echocardiography.[4,16]
Echocardiography in pericardial effusion with tamponade shows right atrial or right ventricular compression, or left atrial compression, decreased left ventricular dimension, and absence of collapse of the inferior vena cava on deep inspiration.[6,25] Echocardiography findings predictive of pericardial tamponade have been reported.[26] Right atrial collapse has a sensitivity of 55% to 60% and a specificity of 50% to 68%. Right ventricular diastolic collapse has a lower sensitivity of 38% to 48% but a higher specificity ranging from 84% to 100%. Because neither finding provides 100% sensitivity and specificity, patients who are clinically symptomatic should have a diagnostic pericardiocentesis, even in the absence of definitive findings on echocardiography.[4,27] One study found right atrial collapse present in only 42% of patients and right ventricular collapse in 62%.[27] Nonetheless, 80% of patients with malignant pericardial effusions had symptomatic relief following pericardiocentesis.
The most definitive test for the diagnosis of cardiac tamponade is equalization of diastolic pressures between all cardiac chambers on right-heart cardiac catheterization.[7] This invasive technique, however, is not necessary to diagnose tamponade.
Electrocardiograms in patients with pericardial effusions typically show diminished QRS amplitude in all leads. A classic but uncommonly seen finding in large effusions with pericardial tamponade is variation in the amplitude of the P wave and QRS complex in successive beats on EKG, referred to as electrical alternans. This finding results from movement of the heart within the pericardial sac.[6] Electrocardiography is not sufficiently sensitive to diagnose pericardial effusions.
Pericardial fluid cytology has an accuracy of 80% to 90% in diagnosing malignant pericardial effusion.[6,28] Lymphomas and mesothelioma have higher false-negative detection rates on cytology evaluation.[6,29] Pericardial fluid cytology has a specificity of up to 100%, but sensitivity ranges from 57% to 100% [10][Level of evidence: II] in patients with a known cancer diagnosis and pericardial fluid. Because nonmalignant causes of pericardial effusion can occur in 42% to 62% of patients with cancer and pericardial fluid, a negative cytology examination of pericardial fluid does not help distinguish malignant from nonmalignant causes. The use of more than one cytological preparation (such as concentrating the sample via cytospin, using special markers, or analyzing DNA content) increases the yield over a single preparation; however, multiple samples using the same technique did not significantly increase the diagnostic yield in a retrospective study of 215 patients.[30] In a survey of 80 samples, measurement of DNA index via flow cytometry of pericardial fluid has a sensitivity of 94.8% and a specificity of 100%, compared with routine cytology with a sensitivity of 98.5% and a specificity of 92.3%.[31][Level of evidence: II] Pericardial biopsy may increase the sensitivity of diagnosing pericardial effusions of malignant origin. Because pericardial effusions usually occur in advanced disease and portend a shorter survival than do other sites of metastatic involvement, however, the relief of symptoms rather than diagnosis should be the overriding factor in determining the extent of the evaluation and the course of treatment. Two studies failed to show a difference in survival in cancer patients with pericardial effusion dependent on the results of fluid cytology.[10,32]
No large controlled, randomized, prospective clinical trials demonstrate the optimal management of malignant pericardial effusions or tamponade. Treatment should therefore be individualized to maximize symptom relief with minimal impact on quality of life. Treatment options include percutaneous pericardiocentesis, pericardial sclerosis, subxiphoid pericardial window, pericardiectomy, or pericardotomy by thoracotomy or video-assisted thoracoscopy. Considerations in the choice of therapeutic option should include relief of tamponade, minimal invasiveness, cost, morbidity, safety, shortened hospitalization for patients with advanced disease, and patient's prognosis.[33][Level of evidence: III]
Large symptomatic malignant pericardial effusions are managed by draining the fluid, unless the goals of therapy dictate a less invasive, conservative approach with concomitant shorter survival that should be balanced against quality-of-life concerns. If treatment is indicated for management of tamponade, percutaneous subxiphoid pericardiocentesis is the treatment of choice in the acute setting. Echocardiography is recommended for catheter guidance.[6,34] Catheter drainage is recommended for large effusions to prevent rapid reaccumulation of fluid and subsequent tamponade and for the anticipated survival of the patient.
Recurrent pericardial effusion occurs in 21% [35] to 50% [33,34] of patients following pericardiocentesis. Limited case series suggest rates of pericardial fluid reaccumulation at 30 days ranging from 5% to 33% after pericardial drainage followed by intrapericardial treatment with sclerosing agents or phosphorus-colloid versus more than 50% of those treated with pericardial drainage alone.[33,34] Treatment options to prevent reaccumulation include intrapericardial sclerosis to obliterate the space within the pericardial sac, or pericardotomy to increase the quantity of fluid drained from the pericardium. The most effective sclerosing agent for malignant pericardial effusions had been tetracycline, with success rates of up to 80%;[6] however, this agent is no longer available as an intravenous drug in the United States. Alternative sclerosants that have been used include doxycycline,[36] bleomycin, thiotepa,[34];[37][Level of evidence: II] carboplatin,[38][Level of evidence: II] mitoxantrone,[39] docetaxel, and radionuclide chromic phosphate. Most cases may require 3 or more treatments to achieve adequate sclerosis.[6] Significant pain is reported by 16% of patients undergoing pericardial sclerosis.[6] Consideration must be given to the side effects of various sclerosing agents, e.g., chest pain and arrhythmias. Of patients undergoing pericardial sclerotherapy, 70% to 80% have no fluid reaccumulation within 30 days of the procedure.[34]
A retrospective comparison of pericardiocentesis with sclerotherapy to open surgical drainage among 60 patients showed similar rates for treatment complications, incidence of recurrent effusion, and survival following treatment in both treatment groups.[40] A retrospective review of 59 patients also found similar success rates, whether patients were managed with surgical subxiphoid pericardial window or by pericardiocentesis with or without sclerosis.[33] Patients who underwent pericardiocentesis followed by pericardial window had the longest survival, with a median of 6 months; however, selection bias toward patients with better performance status undergoing more aggressive surgical techniques may contribute to the reported survival advantage. The surgical procedure group had significantly higher average costs of $4,830 compared with $1,625 for patients managed with pericardiocentesis.[33] Other studies have reported mortality, recurrence, and survival rates for sclerosis that are similar to or slightly lower than those for subxiphoid window or video-assisted thoracoscopy.[40,41];[42][Level of evidence: II][33][Level of evidence: III] Pericardiocentesis with or without sclerotherapy should be considered over more invasive procedures in patients with advanced disease or poor functional status.[43]
Transcutaneous balloon pericardiostomy is another technique that is less invasive than open surgical approaches, which include subxiphoid pericardial windows, thoracotomy with pericardiopleural window formation,[44] and thoracotomy with pericardectomy.
Video pericardioscopy has a diagnostic sensitivity of 97% for detecting malignant effusions.[45] Pericardioscopy also is useful for drainage of loculated effusions.[46][Level of evidence: II] Video-assisted thoracoscopy is preferable to more invasive surgical management and should be considered for patients requiring repeated pericardiocentesis for control of symptomatic effusions.[43]
Check NCI's list of cancer clinical trials for U.S. supportive and palliative care trials about malignant pericardial effusion that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.
Superior vena cava syndrome (SVCS) is an array of symptoms caused by the impairment of blood flow through the superior vena cava (SVC) to the right atrium. Symptoms that prompt suspicion of this syndrome include dyspnea, coughing, and swelling of the face, neck, upper trunk, and extremities. In rare instances, patients may complain of hoarseness, chest pain, dysphagia, and hemoptysis. Physical signs that may be noted on presentation are neck vein distention, thoracic vein distention, edema of the face or upper extremities, plethora, and tachypnea. Rarely, cyanosis, Horner syndrome, and a paralyzed vocal cord may also be present.[1]
SVCS is usually a sign of locally advanced bronchogenic carcinoma. Survival depends on the status of the patient's disease. When small cell bronchogenic carcinoma is treated with chemotherapy, the median survival times with or without SVCS are almost identical (42 weeks or 40 weeks, respectively). The 24-month survival rate is 9% in patients without SVCS and 3% in those with the syndrome. When the malignancy is treated with radiation therapy, 46% of patients who have non-small cell lung cancer experience relief of symptoms compared with 62% of patients who have small cell bronchogenic carcinoma. The 2-year survival rate of 5% is almost the same for both groups.[2]
Most non-Hodgkin lymphoma patients with SVCS respond to appropriate chemotherapy or to combined modality regimens.
Since SVCS was first described by William Hunter in 1757, the spectrum of underlying conditions associated with it has shifted from tuberculosis and syphilitic aneurysms of the ascending aorta to malignant disorders. Almost 95% of SVCS cases described in published modern series are due to cancer; the most common cause is small cell bronchogenic carcinoma, followed by squamous cell carcinoma of the lung, adenocarcinoma of the lung, non-Hodgkin lymphoma, and large cell carcinoma of the lung.[3] A nonmalignant cause of SVCS in cancer patients is thrombosis that is associated with intracaval catheters or pacemaker wires.[4] A rare cause of SVCS is fibrosing mediastinitis, either idiopathic or associated with histoplasmosis.[5] Additional rare causes of SVCS include metastatic germ cell neoplasms, metastatic breast cancer, colon cancer, Kaposi sarcoma, esophageal carcinoma, fibrous mesothelioma, Behçet syndrome, thymoma, substernal thyroid goiter, Hodgkin lymphoma, and sarcoidosis.[6]
Knowledge of the anatomy of the SVC and its relationship to the surrounding lymph nodes is essential to understanding the development of the syndrome. The SVC is formed by the junction of the left and right brachiocephalic veins in the mid third of the mediastinum. The SVC extends caudally for 6 to 8 cm, coursing anterior to the right mainstem bronchus and terminating in the superior right atrium, and extends anteriorly to the right mainstem bronchus. The SVC is joined posteriorly by the azygos vein as it loops over the right mainstem bronchus and lies posterior to and to the right of the ascending aorta. The mediastinal parietal pleura is lateral to the SVC, creating a confined space, and the SVC is adjacent to the right paratracheal, azygous, right hilar, and subcarinal lymph node groups. The vessel itself is thin-walled, and the blood flowing therein is under low pressure. Thus, when the nodes or ascending aorta enlarge, the SVC is compressed, blood flow slows, and complete occlusion may occur.
The severity of the syndrome depends on the rapidity of onset of the obstruction and its location. The more rapid the onset, the more severe the symptoms because the collateral veins do not have time to distend to accommodate an increased blood flow. If the obstruction is above the entry of the azygos vein, the syndrome is less pronounced because the azygous venous system can readily distend to accommodate the shunted blood with less venous pressure developing in the head, arms, and upper thorax. If the obstruction is below the entry of the azygos vein, more florid symptoms and signs are seen because the blood must be returned to the heart via the upper abdominal veins and the inferior vena cava, which requires higher venous pressure.[7]
One study suggested that the general recruitment of venous collaterals over time may lead to remission of the syndrome, although the SVC remains obstructed.[8]
Once SVCS is recognized, prompt clinical attention is important. A diagnosis should be established prior to initiating therapy for the following reasons:[3]
In the absence of tracheal obstruction, SVCS is unlikely to be a life-threatening oncologic emergency, and treatment prior to definitive diagnosis is not justified.
The initial evaluation of the patient should include a chest radiograph to look for mediastinal masses and associated findings, such as pleural effusion, lobar collapse, or cardiomegaly. Computed tomography (CT) scanning of the thorax yields the most useful diagnostic information and can define the anatomy of the involved mediastinal nodes. Venous patency and the presence of thrombi are assessed by using contrast and rapid scanning techniques.[9] Depending on local expertise, contrast or nuclear venography, magnetic resonance imaging, and ultrasound may be valuable in assessing the site and nature of the obstruction.
If bronchogenic carcinoma is suspected, a sputum specimen should be obtained. If the sputum specimen is negative, a biopsy specimen should be taken from the most accessible site that is clinically involved with disease. The biopsy approach depends on the working diagnosis, the location of the tumor, the physiologic status of the patient, and the expertise available at the facility. It may include bronchoscopy, biopsy of palpable cervical or supraclavicular lymph nodes, needle biopsy of a lung mass or mediastinal nodes using either CT or ultrasound guidance, mediastinoscopy, mediastinotomy, median sternotomy, video-assisted thoracoscopy, and conventional thoracotomy.[10] The biopsy findings will help the clinician plan appropriate treatment.
Treatment Options
The treatment of SVCS depends on the etiology of the obstruction, the severity of the symptoms, the prognosis of the patient, and patient preferences and goals for therapy. Radiation therapy or chemotherapy should be withheld until the etiology of the obstruction is clear. The treatments discussed here focus on SVC obstruction caused by a malignant tumor. Since the treatment of malignant obstruction may depend on tumor histology, a histologic diagnosis, if not made earlier, should be made prior to initiation of treatment. Unless there is airway obstruction or cerebral edema, there appears to be no detriment in outcome when treatment is delayed for the assessment.[1,11,12,13,14,15] The following treatment approaches can be used for SVCS.
Medical management
A patient with sufficient collateral blood flow and minimal symptoms may not need treatment. If the lesion is above the azygous vein or if the onset of SVC occlusion is slow enough to allow sufficient collateral circulation, the symptoms and signs may stabilize and the patient may be comfortable enough to forego further therapy. Short-term palliation of a symptomatic patient who does not want aggressive treatment may be achieved by elevating the head and using corticosteroids and diuresis. There are no definitive studies that prove the effectiveness of steroids, although they are potentially useful to treat respiratory compromise. Diuretics may give symptomatic relief of edema but can ultimately cause systemic complications, such as dehydration.[9,16]
Radiation therapy
If the obstruction of the SVC is caused by a tumor that is not sensitive to chemotherapy, radiation therapy should be given. Treatment with larger fractions of radiation is thought to be beneficial in developing a rapid response. One study shows, however, that there is no obvious need for large radiation fraction sizes for the first few radiation treatments as was previously believed.[17] Many fractionation schemes have been used, with doses ranging from 30 Gy in 10 fractions to 50 Gy in 25 fractions. Relief of symptoms in small cell lung cancer is reported to be 62% to 80%, whereas in non-small cell lung cancer, approximately 46% of the patients experienced symptomatic relief.[2,18] In one study, more than 90% of the patients achieved a partial or complete response with a 3-week regimen of 8 Gy given once a week for a total dose of 24 Gy.[19]
Chemotherapy is the treatment of choice for sensitive tumors such as lymphoma or small cell lung cancer. SVCS does not appear to be an independent prognostic factor, and its presence should not change the treatment approach. Rapid initiation of chemotherapy can result in complete and partial response rates of the SVCS of more than 80% in small cell lung cancer patients.[2,18]
It has been suggested that SVCS arises when a thrombus forms in a partially occluded vein. In patients with a documented thrombus in the SVC, treatment may include thrombectomy, with or without tissue plasminogen activator or other thrombolytic agents such as streptokinase or urokinase.[1]
Stent placement
There have been numerous small studies using an intravascular expandable stent to reopen the occluded SVC; however, no prospectively designed comparative studies have been published.[20] The reported response rates have been about 90% or greater.[21][Level of evidence: II] There is no agreement on the need for anticoagulant therapy after stent placement. In one series that used anticoagulant therapy for patients as part of the treatment protocol, there were reports of reocclusion after this therapy was stopped.[22][Level of evidence: II] However, in another study, 17 cancer patients who were treated with stents and who did not have anticoagulant therapy had no occlusions.[23][Level of evidence: II]
Surgical bypass of an obstructed SVC is more appropriate for patients with a benign obstruction than with a malignant obstruction,[24] although surgical bypass has also been used for patients with malignant obstructions.
Psychosocial Considerations
Patients and family members are often frightened and anxious because of the symptoms produced by SVCS, particularly swelling, dysphagia, coughing, and hoarseness. It is important to provide information to patients and family members on the cause of the symptoms and on short-term measures for palliation, especially during the diagnostic period. When aggressive treatment is declined because of the terminal nature of the underlying disease, it may be necessary to teach symptom management approaches to patients and family members.
Because most adult patients who develop SVCS have lung cancer, the treatment and psychologic support approaches that are developed for SVCS should take into account the patient's prognosis and psychologic condition, goals of care, and other symptoms caused by the malignancy.[25]
Pediatric Considerations
As described in other sections of this summary, SVCS refers to the symptoms associated with the compression or obstruction of the SVC; the compression of the trachea is termed superior mediastinal syndrome (SMS). Because SMS and the resulting respiratory compromise frequently occur in children with SVCS, the two syndromes have become almost synonymous in pediatric practice.[26,27] In adults, the trachea and the right mainstem bronchus are relatively rigid structures compared with the vena cava, but in children these structures are more susceptible to compression. In addition, the relatively smaller intraluminal diameters of a child's trachea and bronchus can tolerate little edema before respiratory symptoms occur. Because of this accompanying respiratory component, SVCS in children differs from the adult syndrome and constitutes a serious medical emergency.
The most common symptoms of SVCS in children are similar to those in adults and include coughing, hoarseness, dyspnea, orthopnea, and chest pain. Symptoms that are less common but more serious are anxiety, confusion, lethargy, headache, distorted vision, a sense of fullness in the ears, and, especially, syncope.[26]
SVCS is rare in children and appears at presentation in 12% of pediatric patients with malignant mediastinal tumors.[28,29] The etiology, diagnosis, and treatment of SVCS in children differs from that in adults. Whereas the most frequent cause of SVCS in adults is bronchogenic carcinoma,[3] in children the most frequent malignant cause of the syndrome is non-Hodgkin lymphoma. As in adults, a frequent nonmalignant cause is thrombosis from catheterization for venous access.[26]
A physical examination, chest radiograph, and the medical history of the patient are usually sufficient to establish a diagnosis of SVCS. If lymphoma or other malignant disease is suspected, it is desirable to obtain a tissue sample for diagnosis. However, the procedure to obtain the specimen may involve significant risk and may not be clinically feasible. Children with SVCS have a poor tolerance for the necessary general anesthesia because the accompanying cardiovascular and pulmonary changes aggravate the SVCS, often making intubation impossible. Also, extubation may be difficult or impossible, thus requiring prolonged airway provision (intubation). A CT scan of the chest to determine tracheal size, upright and supine echocardiography, and a flow volume loop may help evaluate anesthetic risk. Because anesthesia use is a serious risk, the diagnosis should be made with the least invasive means possible.[30] Published reports suggest a stepwise approach to diagnosis.[26]
When a malignant mass is the cause of the SVCS, the situation may be a medical emergency with no opportunity to establish a tissue diagnosis. In these cases, the most appropriate course may be to initiate empiric therapy prior to biopsy. The traditional empiric therapy is irradiation, with the daily dose governed by the presumed radiosensitivity of the tumor. After irradiation, respiratory deterioration from the apparent tracheal swelling may occur because of the inability of narrow lumens in children to accommodate edema and because of the greater degree of edema at onset, which is due to the rapid speed at which tumors grow in children. In these situations, a course of prednisone at 10 mg/m2 of body surface area 4 times per day may be necessary.[26]
In addition to radiation, empiric therapy of SVCS has included chemotherapeutic agents incorporating steroids, cyclophosphamide, or both in combination with an anthracycline and vincristine.[26] If the tumor fails to respond, it may be a benign lesion.
If surgery becomes necessary, it should be performed with the patient in the semi-Fowler's position, allowing the surgeon the ability to rapidly change the patient's position to lateral or prone. Cardiopulmonary bypass facilities and a rigid bronchoscope should be available in a standby capacity.[30]
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
If you have questions or comments about this summary, please send them to Cancer.gov through the Web site's Contact Form. We can respond only to email messages written in English.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the pathophysiology and treatment of cardiopulmonary syndromes, including dyspnea, malignant pleural effusion, malignant pericardial effusion, and superior vena cava syndrome. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
National Cancer Institute: PDQ® Cardiopulmonary Syndromes. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/supportivecare/cardiopulmonary/HealthProfessional. Accessed <MM/DD/YYYY>.
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page page.
Contact Us
More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site's Contact Form.
Call 1-800-4-CANCER
For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.
Chat online
The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 8:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.
Write to us
For more information from the NCI, please write to this address:
Search the NCI Web site
The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.
There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.
Find Publications
The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).
Last Revised: 2011-06-30
This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use. How this information was developed to help you make better health decisions.
To learn more visit Healthwise.org
© 1995-2012 Healthwise, Incorporated. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.


text:
Raj TV Sindhu Bhairavi Tamil Drama 26-03-2015 Watch online Tamil Serial Sindhu Bhairavi March 26th 2015 Online Serial Sindhu Bhairavi 26/03/15 Raj TV Program. Sindhu Bhairavi is a Tamil Serial from the Tamil TV Channel being aired from India, Raj TV – Sindhu Bairavi Hindi serial dubbed into Tamil.
Previous Episodes – Click Here
Source 1 – Click on the image below to watch. (Use Google Chrome or Firefox)
Source 2 – Click on the image below to watch.

subset: commoncrawl


text:
Key Issues & Access Control
Key Issues & Access Control provides keys for all campus buildings, except Housing Facilities. Key Issues & Access Control does not supply keys for Housing facilities or dorms, to obtain Housing keys contact them at (360) 867-6132.
Key Issues & Access Control does not provide emergency unlocks or routine building locks and unlocks, contact Police Services at (360) 867-6832 for assistance with those issues.
Key Issues & Access Control Hours of Operation
Monday - Friday 9 am - 12 pm and 1 pm - 4 pm
CLOSED for Lunch 12 pm - 1 pm
Location: Facilities Services - Lab II 1260
Phone: (360) 867-5397
Email: Key Issues & Access Control
Authorization to Issue Keys: Faculty, staff and students will be issued individual keys to offices and assigned laboratories, master keys and all keys to buildings, as needed upon authorization of the person charged with building or area responsibility. The authorizing person must complete a key authorization form, available at Key Issues & Access Control or send an e-mail detailing the need. The length of time that the key is to be issued is determined by the authorizer or by Key Issues & Access Control.
To Obtain Key(s): The person being issued the key(s) will submit the Key Authorization Form with the necessary signature(s) to Key Issues & Access Control, and show their Evergreen College identification card to Key Issues & Access Control staff.
To Return Key(s): Keys must be returned to Key Issues & Access Control by the due date, or by the last day of employment, whichever occurs first.
Due Date Extension(s): The authorizer must resubmit a Key Authorization Form to Key Issues & Access Control, or send an email, with the new due date.
Lost, Stolen and Unreturned Keys: Lost, Stolen and Unreturned Keys: When loss due to negligence or theft is reported, a key charge will be levied at the rate of $25 for a regular key, $20 for electronic key cards and key fobs, $50 for a sub-master key, $100 for a master key, and $200 for a grand master key.
Complete a lost key payment form, available at Key Issues & Access Control. Take the completed form to the cashier and pay the required fine. Return the receipt along with the form to Key Issues & Access Control so the individual's file can be updated. Fine is refunded minus $10.00 service charge if the lost or stolen key is found and returned to Key Issues & Access Control within 90 days of initial billing date.
For students, if keys are not returned by the indicated return date, Key Issues & Access Control will advise Students Accounts to bill the individual at the lost key rate. For all others, a bill for the amount of the lost key rate will be charged to the key holders account.
Key Issue Procedures
The revised Key Issue Procedures can be found here: (PDF)
Appeals Process
If a Key Holder believes that they should not be held responsible for their lost key(s) or a charge has been made in error, they have the right to appeal the lost key charges.
Appeals Process
Key Control Office Disclosure
Keys are the property of The Evergreen State College. Key Issues & Access Control reserves the right to refuse Keys to individuals with lost, delinquent or unpaid key fines on their account.


text:
wildlifeorphanage.org Terms and Conditions
wildlifeorphanage.org offers this Web site, including all information, software, products and services available from this Web site or offered as part of or in conjunction with this Web site wildlifeorphanage.org, to you, the user, conditioned upon your acceptance of all of the terms, conditions, policies and notices stated here. wildlifeorphanage.org reserves the right to make changes to these Terms and Conditions immediately by posting the changed Terms and Conditions in this location.
Your continued use of the Web site constitutes your agreement to all such terms, conditions and notices, and any changes to the Terms and Conditions made by wildlifeorphanage.org.


text:
Ateco Pastry Bag Decorating Kit
Ideal for decorating cookies, cakes, cupcakes and pastries, this kit contains the essential tools for creating countless borders, scrolls, flowers and lettering.
- Durable stainless-steel tips can be used again and again.
- Six tips let you create outlines and fills, writing, beads, dots, stems, flower petals, stars, zigzags, shells, ropes, puffs, rosettes, scrolls and leaves.
- Two durable nylon bags can be hand-washed and used for countless baking projects.
- Plastic coupler secures tips during use and lets you use multiple tips with the same bag.
- Comes with recipes for buttercream and royal icings.
- Instructions included.
- Made by Ateco, producers of professional-quality pastry tools since 1905.
Dimensions & More Info
Set includes:
- One 6" x 10" nylon decorating bag.
- One 7" x 12" nylon decorating bag.
- 1 plastic coupler set.
- 1 #4 round tip.
- 1 #16 open-star tip.
- 1 #32 scalloped tip.
- 1 #48 basket-weave tip.
- 1 #104 petal tip.
- 1 #352 leaf tip.
Additional information
- Nylon bags.
- Plastic coupler.
- Stainless-steel tips.
- Approx. 1 1/4" long.
- Made in Korea.
Use & Care
- Hand-wash.
Shipping Information
UPS can deliver most in-stock items within 3–5 business days. UPS is unable to deliver to P.O. boxes.
Shipping Rates
The shipping rate varies depending on your order total and shipping destination. View Shipping Options and Charges.
Next Day Delivery
For an additional charge of $26 per address, we can expedite delivery to most destinations. This service is not available for some oversize items, items shipped directly from the supplier (including perishable and custom-manufactured items), out-of-stock items and items to be shipped outside the contiguous 48 states.
Orders received by 9:00 p.m. ET Monday through Thursday will arrive the next business day; orders placed Friday through Sunday will arrive on the following Tuesday.
Return Policy
At Williams Sonoma, we take great pride in the quality and craftsmanship of our products. Attention to design, materials, safety and construction are our priority. Upon receipt, please inspect your purchase and notify us of any damage; we will arrange for a prompt replacement.
If within 30 days, you are dissatisfied for any reason, you may return your purchase for a refund of the merchandise value. An original receipt or gift receipt is required for all returns and exchanges. Returns with a gift receipt will be refunded in the form of a Merchandise Credit for the amount indicated on the gift receipt. Returns with original receipt will be refunded in the original form of payment, cash and check refunds over $100 will be issued as a company check (may take 14 business days from time of request).
For all cutlery returns (knife sets, single knives, cutting boards, knife sharpeners and knife storage), please contact us at 888.922.4108 to initiate the return.
We cannot accept returns on monogrammed, personalized, special-order items, custom upholstery, food, items shipped direct from the vendor or on items damaged through normal wear and tear. Final sale items ending in .97 or .99 cannot be returned.
Made to Order and Final Sale Furniture items are non-returnable and cannot be cancelled once the order is placed.
For returns of items purchased from your Williams Sonoma Gift Registry, we will gladly provide a refund or exchange for the merchandise within 90 days of your event or within 90 days of purchase, whichever date is later. View Full Returns Policy.
Ateco Pastry Bag Decorating Kit
|Delivery Surcharge
|Ateco Pastry Bag Decorating Kit


text:
Arkansas Safety Expert Witnesses
Arkansas Accident Reconstruction & Safety Expert Witness Listings
You may limit your search for Safety expert witnesses to a specific area by selecting a state from the drop down box.
Expert Witnesses
List Your Qualifications by Clicking Here
Featured Experts
Mr. White is an experienced retail executive, serving as Chief Executive Officer and Chief Operations Officer, in several different retail companies. Mr. White has grown in his career from store manager, district manager, regional operations director,... Learn More ›
Dr. McCartney is a Senior Safety Engineer and Expert Witness. Dr. McCartney holds certifications as a: Certified Safety Professional, Registered Professional Industrial Hygienist, and Certified Safety Instructor with 38 years of experience in both safety... Learn More ›
Dr. Fagel is a safety and disaster management consultant. He specializes in industrial safety, OSHA, safety, FEMA, security, transportation, and the food industries. He spent over 100 days at ground zero following the September 11, 2001 attacks. Dr.... Learn More ›
Dr. Abraham has over forty years of international experience consulting to insurance companies, municipalities, government agencies, and the legal profession. He has consulted in more than 3,500 matters involving human factors, safety, personal injury... Learn More ›
Dr. John Murphy is founder and president of REA, an occupational, environmental and public health consultancy with offices in Cambridge, Toronto, Ottawa and the Caribbean. He has 33 years career experience involving more than 16,000 projects for 3,000+... Learn More ›
Russ Rasnic, P.E. (Ryan Forensics, PLLC)
Location: Arkansas
Areas of Expertise: Ryan Forensics division of Ryan Engineering, Inc. is a full service firm encompassing mechanical, electrical, and electromechanical engineering disciplines, as well as ergonomics and human factors. We...
Paul Chen (PC Squared Consultants - Consumer Product (Nonfood) Safety, Regulatory and Retail Compliance, Quality Assurance and Control Consultant and Expert)
Location: Arkansas
Areas of Expertise: Paul Chen is a consumer product (non-food) safety, regulatory and retail compliance, quality assurance and control, 3rd party lab testing / inspection / auditing, CPSC (Consumer Product Safety Commission),...
Consolidated Consultants
Location: Multiple Locations
Areas of Expertise: Consolidated Consultants (CCc) continues to deliver high quality expert witness and medical expert witness referrals nationwide since 1995. CCc is the only referral service where you can view the full,...
Gary E Kilpatrick (The Kilpatrick Group, PA)
Location: Multiple Locations
Areas of Expertise: Who is The Kilpatrick Group? The Kilpatrick Group is a forensic engineering and consulting firm. We provide forensic engineering services in three main practice areas Division I: Motor Vehicle...
Jeffery H. Warren, Ph.D., P.E., CSP (The Warren Group, Inc.)
Location: Multiple Locations
Areas of Expertise: *Available Nationwide* Dr. Jeffery Warren is Chief Engineer and CEO of The Warren Group. A licensed professional engineer in 12 Southeastern states, he holds a Bachelor of Science in Mechanical Engineering...
Ronald D Schaible, CIH, CSP, CPE (Robson Forensic Inc.)
Location: Multiple Locations
Areas of Expertise: Ron Schaible, CIH, CSP, P.E. is Certified in the Comprehensive Practice of Industrial Hygiene (CIH), Certified Safety Professional (CSP), a Registered Professional Engineer #36714-Safety (Massachusetts),...
Peter Chen, M.S.M.E, M.B.A., P.E., CFEI (ARCCA, Inc.)
Location: Multiple Locations
Areas of Expertise: PETER CHEN, M.S.M.E., M.B.A., P.E., CFEI, ACTAR, is a Mechanical Engineer specializing in Accident Reconstruction, Fire Cause/Origin, Product Failure/Liability, Car and Truck Failure Analysis, Industrial...
Scott Burton, Certified Playground Safety Inspector (Safety Play, Inc.)
Location: Multiple Locations
Areas of Expertise: Nationwide. FREE AIR FARE (restrictions apply). Unused retainers are refunded (above case min.)! Mr. Burton is an ex-manufacturer experienced in testimony, manufacturing, design, planning, installation,...
ForensisGroup, Inc. (The Expert of Experts)
Location: Multiple Locations
Areas of Expertise: For over 20 years, ForensisGroup has provided the nation's top law firms, insurance agencies, government entities and many other industries with highly qualified expert witnesses and consultants. Experts...
Stephen E. Fournier, P.E., NCEES (Robson Forensic, Inc.)
Location: Multiple Locations
Areas of Expertise: STEPHEN E. FOURNIER, P.E., NCEES Construction Injury, Construction Equipment, Workplace Safety, Ladder Expert Steve has over 35 years in the construction field and has performed more than 1,000 forensic...
Steve Hunt, CPCU, ARM, CXLT (The Warren Group, Inc.)
Location: Multiple Locations
Areas of Expertise: *Available Nationwide" for Slips, Trips and Falls, Construction Related Accidents, Construction Falls Steve Hunt is a Senior Safety Consultant of The Warren Group. He has extensive expertise in investigating...
Gregory H. Pestine, P.E. (Robson Forensic, Inc.)
Location: Multiple Locations
Areas of Expertise: Gregory H. Pestine, PE Quality Control / Assurance, Construction, Construction Safety, and Civil Engineering Expert Greg has nearly 30 years of experience in various roles in many types of construction...
Safety Expert Witnesses by State
All States, Alaska, Alabama, Arkansas, Arizona, California, Colorado, Connecticut, District of Columbia, Delaware, Florida, Georgia, Hawaii, Iowa, Idaho, Illinois, Indiana, Kansas, Kentucky, Louisiana, Massachusetts, Maryland, Maine, Michigan, Minnesota, Missouri, Mississippi, Montana, North Carolina, North Dakota, Nebraska, New Hampshire, New Jersey, New Mexico, Nevada, New York, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Virginia, Vermont, Washington, Wisconsin, West Virginia, Wyoming


text:
History Means More Than Money to Die-Hard Mopar Racer Milburn Varner
For some, bragging rights might be made up of horsepower numbers or elapsed times, but for Milburn Varner, it consists of gloriously unrestored Mopars and lots of parts to go with them. While his age prevents him from doing all the fun stuff he did in the '60s and '70s, he still loves his old cars and still has most of them. Milburn started drag racing in 1961 with a '53 Pontiac, but most of his racing days were spent behind the wheel of a Mopar. He has hundreds of great stories about his drag-racing days, but he's also aware of the harsh reality that caused him to stop racing in 1974.
Running in the Super Stock ranks, Milburn and brother-in-law David Rehring raced at least twice a week at various Southeastern dragstrips and truly shared a love for the sport. Milburn told us, "We ate, drank, and slept drag racing for 12 years." He and David would swap driving duties every night they raced, and they worked like crazy to get the car ready every week. They lived in southeast Tennessee, which had an abundance of dragstrips within a 100-mile radius, so they never had trouble finding a race to attend. Their home track was Brainerd Optimist Dragstrip (NewBrainerdOptimist Dragstrip.com), which is still in operation in Ringgold, Georgia, but they also raced at many other Tennessee, Georgia, Alabama, and North Carolina tracks.
Their grassroots race team started with a '63 Plymouth Belvedere, a Max Wedge car. This car laid the ground work for their drag-racing addiction, and it even inspired a name for their cars: Drag Addicts. Milburn admits they had the most fun with this car, because it was a top contender and rarely gave them any problems. Milburn and David barnstormed the local tracks and raked in some serious money for the time. One of the most amazing parts of Milburn's collection is his notebook inscribed with "Drag Racing Ledger," which documents every dime they spent won in the '67 season. If you want a real view of grassroots drag racing in the '60s, this is it.
After replacing the '63 with a one-year-only '64 Max Wedge, they sold it to buy a new '70 'Cuda. It was In Violet purple, and they ordered it with a 440 Six Pack and automatic transmission. On the first trip to the dragstrip, the speedometer wrapped completely around due to the low rearend gearing, so they disconnected the cable. It has 149 miles on the odometer after four years of racing, so you can do the math on that one. The car was never titled and never saw any street driving after its initial trip home from the dealership.
Gunning for the big dogs in Super Stock D Automatic, Milburn and David gave the 440ci big-block a good tune-up and hoped to be a strong contender. Giving in to the Hemi hype, Milburn went on the hunt for a donor car. And while it seems crazy now, Milburn yanked the original 426ci Hemi out of a '67 Plymouth Belvedere GTX convertible, one of only 17 built. He still owns the Belvedere and still owns the 'Cuda, which has not been touched since its final race in 1974.
So why quit? The first nail in the coffin was his brother-in-law's fading interest in racing. As Milburn continued to race the 'Cuda, it never ran as good as he thought it should. Although he hung up his helmet, he never sold any of his cars or parts, because he thought he might get back into racing at some point. As the racing world changed, Milburn realized he had been priced out of competition, and it didn't look nearly as fun. Luckily, all of the cars and parts have been under a roof, so they're in good shape. The 'Cuda still wears its In Violet paint with all of the lettering and sponsor decals still in place.
The 'Cuda's original Six Pack engine sits on an engine stand, alongside several Hemi and wedge engines in Milburn's collection. He also has the old '63 Max Wedge car, as well as a '66 Plymouth Belvedere street Hemi car.
Milburn also has a '66 Plymouth Belvedere, which is a 426 street Hemi car. It's a numbers-matching car, and it's one of the more driveable Mopars in his collection.
Almost 40 years after his final race, Milburn's love for all things Mopar is still very strong. He's retired, and he loves to talk racing, so it's a joyous occasion to hang out with a man who has such an incredible collection of cars, parts, and history. Milburn says, "I ain't sellin' this stuff–it's all about braggin' rights, and the money don't mean as much as these old cars and all of the good memories they gave me."


text:
Personalize it? Select one...
The Hebrew-Greek Key Word Study Bible
is a complete English Bible text for cross-reference study to the
original languages from which the Bible was translated.
System of Study
'The Hebrew-Greek Key Word Study Bible is my favorite.
I can give it no higher recommendation than to say it is the Bible I
have raised my daughters to use.'
—Beth Moore, Living Proof Ministries, Houston, Texas
'I value Dr. Zodhiates' Hebrew-Greek Key Word Study
Bible as a great treasure in studying the words of Scripture and the
depth and breadth of their meaning and application. It is my constant
companion and the next best thing to my many personal conversations with
him. I am especially grateful for the lexical aids to the Old and New
Testaments. This one-volume library is a must for any believer who wants
a 'ready-to-use' reference guide for the pure and powerful words of
—Bill Gothard, President, Institute of Basic Life
About the Editors:
In 1946, he came to the United States at the invitation of the
American Mission to the Greeks, Inc. At that time, there were two
part-time employees who met in a small, one-room office. Dr. Zodhiates
became president of this organization in 1966. Now known as
AMG International('Advancing the Ministries of the
Gospel'), it carries on a worldwide evangelistic and relief ministry and
has its headquarters in Chattanooga, Tennessee.
Dr. Zodhiates is a recognized authority on the Greek New Testament,
and has edited an edition of the Modern Greek New Testament that was
published by the Million Testaments Campaign and the American Bible
Society. He is the author of numerous exegetical books and booklets in
both the Greek and English languages. In addition, he is heard daily on
the New Testament Light radio program, released over a network of
stations across the United States and Canada.
Dr. Warren Baker is the Senior Editor of AMG
Publishers in Chattanooga, Tennessee. He is co-author of The Complete
Word Study Dictionary: Old Testament, and the general editor of The Complete
Word Study Old Testament. He also served as managing editor of
The Complete Word Study New Testament, The Compete Word Study
Dictionary: New Testament, and The Hebrew-Greek Key Word Study
Dr. Baker holds several degrees: B.A., Clearwater Christian College;
M.Div., S.T.M., and D.R.E., Faith Theological Seminary. He served as
Assistant Professor of Old Testament at Faith Seminary until he began
his career in Christian publishing nearly twenty years ago.
All Bibles guarantees all products to be free from defects in material or workmanship for 30 days.
Most manufacturers and publishers offer limited warranties on their products from one year to life.
For more information, see our returns policy.
All products sold on this site are guaranteed to be free of defects in materials and workmanship unless otherwise noted. All Bibles will replace or repair any defective item
within 30 days, and most Publishers and Manufacturers offer extended warranties on their products--some of which are guaranteed for life!
This website uses high-encryption technology, is independently audited by Trustwave to ensure compliance with credit card industry regulations and standards,
and is also verified secure by Godaddy.


text:
There's a lot of coastline wrapped around this isle - over ten thousand miles of it, in fact. Factor in Britain's astonishing variety of landscapes and you have a country whose beaches range from epic strands to tiny notches chipped from cliffs, wilderness islands to prim Edwardian resorts. Here's ten of the best beaches in Britain - add your own to the list below.
Porthcurno, Cornwall
Small but exquisitely formed, Porthcurno's wedge of white sand, surrounded by ragged cliffs and framing a sapphire bay, creates an improbably idyllic scene. Nor is Porthcurno just a pretty face; the cliff-top Minack Theatre hosts open-air performances, while a museum celebrates the birth of transatlantic telegraphy here in 1870. Staggering beauty, culture and history all in one spot.
West Wittering, West Sussex
Keith Richards may have a beach hut here, but West Wittering excels in peace'n'quiet rather than rock'n'roll. Swish through the dunes (pictured at the top of the article) to emerge onto 55 acres of unspoilt sand that somehow swallows 10,000 visitors on sun-drenched summer bank holidays. Wind- and kitesurfers love it. So do kids, splashing in sandy pools or crabbing at low tide. Everyone else loves it, too – just dawdling or gazing out at the Channel with a cuppa. Keith's probably doing the same.
Par Beach, St Martin's, Isles of Scilly
© Panaspics/Shutterstock
St Martin's seems to lie at the end of the world. Rawer and wilder than neighbour Tresco, this is an island for connoisseurs, a fertile fuzz of green fringed by sugar-white beaches that swell as the tide drops. Don't forget your mask and snorkel: seals bob among kelp forests in the clearest bluest water in the archipelago.
Barafundle, Pembrokeshire
Royal Ascot? No, thanks. Glyndebourne? Too noisy. In 2006, readers of Country Life magazine, the glossy bible for posh pastoral folk, named this sensational beach scalloped into the Pembrokeshire cliffs as their favourite British picnic spot. Space has a lot to do with it; the walk here from Stackpole Quay keeps crowds to a minimum and gives Barafundle the frisson of a shared secret. Shallow seas and shelter from prevailing winds also score points. But the clincher? Superlative sands that are just perfect for sand castles.
Bamburgh, Northumberland
There's no better model for sand-castle-making than the storybook silhouette of Bamburgh Castle. It rises behind the pale sand of this pristine beach, which stretches into the distance beneath a pale pure sky and extends a mile out to sea at low water. Add in the romantic outline of Holy Island at its northern end and it is a magnificent vista fit for Viking longships, one not nearly as well known as it should be. (That's half the reason to go.)
Bantham, Devon
© ian woolcock/Shutterstock
With its pristine sands, old thatched cottages and lack of commercialism, the south Devon village of Bantham is a small timewarp, preserved from much development over the past sixty years by its staunchly protective owners, the Evans Estate. The waves are popular with surfers but the beach, with its shallow waters and wide expanse of sand, is also good for the bucket-and-spade brigade, and there are rock pools and dunes to explore.
Scarista, Harris, Western Isles
Beaches are about escapism, and Scarista on the Isle of Harris has it in buckets and spades. As if the adventure of getting to the Outer Hebrides wasn't enough, the wide-open vistas of rolling hills and empty seascapes from this raw, elemental beach give you a walk on the wild side at the outer edge of civilization. Sparkling white sands and vivid blue water add to the appeal.
Holkham, Norfolk
Let's hear it for Holkham: white-gold sands (a rarity among Norfolk's more usual shingle), shells and starfish, a fringe of aromatic pine woodland and a nature reserve teeming with saltings and water birds. Gwyneth Paltrow strode its shoreline alone in the closing scene of Shakespeare in Love, and for good reason: there's an introspective intensity to this minimalist landscape, a romantic Turner-esque vista of empty sea and sky stung by the North Sea breeze.
Crosby, Merseyside
A public petition in 2007 ensures that Crosby remains the permanent gallery for artist Antony Gormley's Another Place installation; a hundred life-size iron men who stare to the open sea either side of the tide line. Some are now half-buried in sand. Others are dressed in a coat of weeds. Gormley says his work tackles themes of migration and illustrates that every landscape has a social dimension. We say it creates the most haunting beach in Britain.
© philip openshaw/Shutterstock
Studland Bay, Dorset
Studland Bay is not as famous as the Jurassic Coast (which starts at the tip of this lovely bay as Old Harry's Rocks) – reason enough to visit. Another is the astonishing natural beauty preserved under the aegis of the National Trust. Tramping along trails through dunes and woods behind the bay you may spy deer, while in the heath you could uniquely spot all six British reptiles. There's a catch, of course: walking the trail means dragging yourself away from Middle Beach, with its charmingly ramshackle beach-hut café and sheltered water perfect for swimming.
Offer your own top beaches in Britain below.
Make The Most Of Your Time In Britain includes 500 great British experiences - find out more.
Check out the best beaches in Italy >


text:
Ford Out With Fractured Femur
ANNECY, France (Jan. 16) – U.S. Ski Team athlete Tommy Ford (Bend, OR) is recovering at a hospital in Annecy after surgery on a fractured right femur. Ford suffered the injury while freeskiing Tuesday in La Clusaz. According to U.S. Ski Team Medical Director Kyle Wilkens, he was treated on the scene then evacuated by helicopter to Annecy where he underwent surgery overnight. U.S. Ski Team partner Global Rescue is providing support. He is expected to remain in Annecy until he is stable for transport back to the USA. A 2010 Olympian and 2011 World Championships team member, Ford has captured eight U.S. titles across the last three seasons.


text:
You've probably dressed up your pet before, so why not dress up your drink? Prevent that icky feeling you get from holding a condensation-soaked iced coffee with our latest obsession – Freakers. They're like sweaters for your favorite frosty beverage and they're part of our latest series, Made in the USA.
Few things are worse than that cold, drippy sensation that accompanies clutching a cold frappuccino or iced tea. Beyond that, those little cardboard sleeves sometimes just don't cut it. With that in mind, Freaker USA has solved this problem with their array of fun and feisty beverage insulators. With names like "Baberaham Lincoln" and "The Dude", they have somehow managed to take a mundane object and make it cool.
Which ones is your favorite? Post a comment or stop by select Barnes & Noble College campus bookstores and pick one up!


text: The Lawrence University Archives promotes understanding of Lawrence and Milwaukee-Downer College history by collecting, preserving, and making accessible unique materials that document this history. It is the official repository for University records of enduring value. In supporting the research needs of Lawrence students, faculty, staff, alumni, and members of the wider community, the Archives helps fulfill the teaching and learning mission of the University.