USFDA approves New drug KEYTRUDA ( used in Melanoma) for NSCLC.

By Dr Deepu

• The U.S. Food and Drug Administration approved Merck & Co.’s Keytruda for the treatment of the most common form of lung cancer, the second of a costly new wave of immune-boosting drugs to be cleared for one of the deadliest cancer types.
• The FDA cleared Keytruda for use in patients with non-small-cell lung cancer whose tumors contain a certain level of a protein known as PD-L1.
• In early 2015, Merck & Co.'s drug Keytruda has been approved to treat melanoma, a type of skin cancer. Keytruda's FDA approval as a lung cancer treatment was announced on Oct. 2, 2015.
• Also known as 'pembrolizumab', Keytruda is designed for patients with advanced non-small cell lung cancer (NSCLC). Patients who suffer from the illness have tumors with a specific protein called 'programmed cell death protein 1' or PD-L1.
•  Keytruda contains an antibody which targets another protein called PD-1. When PD-L1 and PD-1 bind together, PD-1 lowers T lymphocytes or T-cells in the immune system. 
• Normal levels of T-cells help the body fight cancer cells. Evidently low levels of T-cells are prominent in HIV/AIDS patients.
• By blocking the interaction between proteins PD-L1 and PD-1 in the molecular pathway, Keytruda could help the immune system to fight off cancer cells.
• An accompanying diagnostic, the PD-L1 IHC 22C3 pharmDx test, has also been approved by the FDA. This is the first diagnostic test to detect PD-L1 proteins in lung cancer patients.

Plombage - An Obsolete Technique of Historical Importance in treating TB

By Dr Deepu

Chest X Ray of Plombage using Lucite Balls

CT Thorax of the same Patient

Plombage was a surgical method used prior to the introduction of anti-tuberculosis drug therapy to treat cavitary tuberculosis of the upper lobe of the lung. The term derives from the Latin word "plumbum" (lead) and refers to the insertion of an inert substance in the pleural space. The technical medical term for plombage is extraperiosteal or extrapleural pneumonolysis.

The underlying theory of plombage treatment was the belief that if the diseased lobe of the lung was physically forced to collapse, it would heal quickly. There were positive results in tuberculosis therapy following plombage in the decades of the 1930s, 40s and early-50s. However, with the introduction of drugs which were effective in destroying the tuberculosis bacterium (Mycobacterium tuberculosis), plombage treatment fell into disfavor. In addition, complications of plombage began to appear in patients who had been so treated. These complications included hemorrhage, infection and fistulization  of the bronchus, aorta, esophagus and skin.

The technique involved surgically creating a cavity underneath the ribs in the upper part of the chest wall and filling this space with some inert material. A variety of substances were typically used and included air, olive or mineral oil, gauze, paraffin wax, rubber sheeting or bags and Lucite balls. The inserted material would force the upper lobe of the lung to collapse.

NEJM LINKS FOR LUCITE BALLS

link1

Link2

Spotter- Give your diagnosis

By Dr Deepu
Observe the images properly and answer the following questions.
1. What is your diagnosis?
2. What is the radiological appearance?
3. When and why it is done?

See Answer 
Here

NEJM LINKS FOR LUCITE BALLS
link1
Link2



Image courtesy: Dr Shravan.

Asthma Patients Treated With Bronchial Thermoplasty May Have Decreased Airway Smooth Muscle Mass And Type-1 Collagen Deposition Underneath Basement Membrane

By Dr Deepu

Healio (9/22) reports that research indicated that individuals “with asthma treated with bronchial thermoplasty demonstrated decreased airway smooth muscle mass and type-1 collagen deposition underneath the basement membrane.” The findings were published in the Annals of the American Thoracic Society.

Spotter- Give your diagnosis.

By Dr Deepu.
A chronic smoker is admitted with us, his complaints are right sided chest pain and facial pufiness noticed every day when he wakes up in the morning.
Here is the CT thorax.
What is your diagnosis?

For answer click here

Superior Venecaval Syndrome

By Dr Deepu
SVCS will be discussed under the sub headings given below, select specific subheading to read further.
Images
Definition
History
Pathophysiology
Presentation and Findings
Causes
Diagnostic Workup
Management

Images:

Normal Anatomy

SVC Obstruction

Definition

Superior Venecaval Syndrome

By Dr Deepu
Images
Definition
History
Pathophysiology
Presentation and Findings
Causes
Diagnostic Workup
Management

Management

In the management of superior vena cava syndrome (SVCS), the goals are to relieve symptoms and to attempt cure of the primary malignant process.

Only a small percentage of patients with rapid-onset obstruction of the superior vena cava (SVC) are at risk for life-threatening complications.

Patients with clinical SVCS often gain significant symptomatic improvement from conservative treatment measures, including elevation of the head of the bed and supplemental oxygen. 

Emergency treatment is indicated when brain edema, decreased cardiac output, or upper airway edema is present.

Corticosteroids and diuretics are often used to relieve laryngeal or cerebral edema, although documentation of their efficacy is questionable.

Radiotherapy has been advocated as a standard treatment for most patients with SVCS. It is used as the initial treatment if a histologic diagnosis cannot be established and the clinical status of the patient is deteriorating; however, reviews suggest that SVC obstruction alone rarely represents an absolute emergency that necessitates treatment without a specific diagnosis.

The fractionation schedule for radiotherapy usually includes two to four large initial fractions of 3-4 Gy, followed by daily delivery of conventional fractions of 1.5-2 Gy, up to a total dose of 30-50 Gy. The radiation dose depends on tumor size and radioresponsiveness. The radiation portal should include a 2-cm margin around the tumor.

During irradiation, patients improve clinically before objective signs of tumor shrinkage are evident on chest radiography. Radiation therapy palliates SVC obstruction in 70% of patients with lung carcinoma and in more than 95% of those with lymphoma.

In patients with SVCS secondary to non–small-cell carcinoma of the lung, radiotherapy is the primary treatment. The likelihood of patients benefiting from such therapy is high, but the overall prognosis of these patients is poor.

Chemotherapy may be preferable to radiation for patients with chemosensitive tumors. 

When SVCS is due to thrombus around a central venous catheter, patients may be treated with thrombolytics (eg, streptokinase, urokinase, or recombinant tissue-type plasminogen activator) or anticoagulants (eg, heparin or oral anticoagulants).

Removal of the catheter, if possible, is another option, and it should be combined with anticoagulation to prevent embolization. These agents are most effective when patients are treated within 5 days after the onset of symptoms.

Dexamethasone

Important therapeutic agent in a number of malignant diseases. Exerts biologic action predominately by binding to glucocorticoid receptor. For symptomatic management in tumor-associated edema.

Thrombolytics

The potential benefits of thrombolytics for the treatment of pulmonary embolism include fast dissolution of physiologically compromising pulmonary emboli, quickened recovery, prevention of recurrent thrombus formation, and rapid restoration of hemodynamic disturbances. For deep vein thrombosis, lysis of the thrombus can prevent pulmonary embolism and permanent pathologic changes, such as venous valvular dysfunction and postphlebitic syndrome.eg Urokinase

Anticoagulants

In superior vena cava syndrome (SVCS), these agents are used mainly to prevent pulmonary embolism from superior vena cava (SVC) thrombus.

Eg: Heparin and Warfarin

Superior Venecaval Syndrome

By Dr Deepu
Images
Definition
History
Pathophysiology
Presentation and Findings
Causes
Diagnostic Workup
Management

Diagnostic workup

Patients presenting with overt superior vena cava syndrome (SVCS) may be diagnosed by means of physical examination alone. However, subtle presentations necessitate diagnostic imaging.

Chest X Ray

Chest radiography may reveal a widened mediastinum or a mass in the right side of the chest. Only 16% of the patients studied by Parish et al in 1981 had normal findings on chest radiography.

CT Scan

Computed tomography (CT) has the advantage of providing more accurate information on the location of the obstruction and may guide attempts at biopsy by mediastinoscopy, bronchoscopy, or percutaneous fine-needle aspiration. It also provides information on other critical structures, such as the bronchi and the vocal cords.

A CT scan of the chest is the initial test of choice to determine whether an obstruction is due to external compression or due to thrombosis. The additional information is necessary because the involvement of these structures requires prompt action for relief of pressure.

Magnetic resonance imaging (MRI)

Magnetic resonance imaging (MRI) has not yet been sufficiently investigated in this setting, but it appears promising. It has several potential advantages over CT, in that it provides images in several planes of view, allows direct visualization of blood flow, and does not require iodinated contrast material (an especially important characteristic when stenting is anticipated).

MRI is an acceptable alternative for patients with renal failure or those with contrast allergies. Potential disadvantages include increased scanning time with attendant problems in patient compliance and increased cost.

venography

Invasive contrast venography is the most conclusive diagnostic tool (see the image below). It precisely defines the etiology of obstruction. It is especially important if surgical management is being considered for the obstructed vena cava.
Management 

Superior Venecaval Syndrome

By Dr Deepu
Images
Definition
History
Pathophysiology
Presentation and Findings
Causes
Diagnostic Workup
Management

Causes

More than 80% of cases of SVCS are caused by malignant mediastinal tumors.

 Bronchogenic carcinomas account for 75-80% of all these cases, with most of these being small-cell carcinomas.

 Non-Hodgkin lymphoma (especially the large-cell type) account for 10-15%. Causes of SVCS appear similar to the relative incidence of primary lung and mediastinal tumors

. Rare malignant diagnoses include Hodgkin disease, metastatic cancers, primary leiomyosarcomas of the mediastinal vessels, and plasmocytomas.

Nonmalignant conditions that can cause SVCS include the following:

·         Mediastinal fibrosis

·         Vascular diseases, such as aortic aneurysm, vasculitis, and arteriovenous fistulas

·         Infections, such as histoplasmosis, tuberculosis, syphilis, and actinomycosis

·         Benign mediastinal tumors such as teratoma, cystic hygroma, thymoma, and dermoid cyst

·         Cardiac causes, such as pericarditis and atrial myxoma

·         Thrombosis related to the presence of central vein catheters

Diagnostic Workup

Super Venecaval Syndrome

By Dr Deepu
Images
Definition
History
Pathophysiology
Presentation and Findings
Causes
Diagnostic Workup
Management

Presentation

Early in the clinical course of superior vena cava syndrome (SVCS), partial obstruction of the superior vena cava (SVC) may be asymptomatic, but more often, minor symptoms and signs are overlooked.

As the syndrome advances toward total SVC obstruction, the classic symptoms and signs become more obvious.

 Dyspnea is the most common symptom, observed in 63% of patients with SVCS.

Facial swelling, head fullness, cough, arm swelling, chest pain, dysphagia, orthopnea, distorted vision, hoarseness, stridor, headache, nasal stuffiness, nausea, pleural effusions, and light-headedness can be seen.

Findings

The characteristic physical findings of SVCS include venous distention of the neck and chest wall, facial edema, upper extremity edema, mental changes, plethora, cyanosis, papilledema, stupor, and even coma. Bending forward or lying down may aggravate the symptoms and signs.

Causes

Superior Venecaval Syndrome

By Dr Deepu

Definition
History
Pathophysiology
Presentation and Findings
Causes
Diagnostic Workup
Management

Pathophysiology:

The SVC is the major drainage vessel for venous blood from the head, neck, upper extremities, and upper thorax. It is a thin-walled, low-pressure, vascular structure. This wall is easily compressed as it traverses the right side of the mediastinum.

 It is located in the middle mediastinum and is surrounded by relatively rigid structures such as the sternum, trachea, right bronchus, aorta, pulmonary artery, and the perihilar and paratracheal lymph nodes. It extends from the junction of the right and left innominate veins to the right atrium, a distance of 6-8 cm.

Obstruction of the SVC may be caused by neoplastic invasion of the venous wall associated with intravascular thrombosis or, more simply, by extrinsic pressure of a tumor mass against the relatively thin-walled SVC. Complete SVC obstruction is the result of intravascular thrombosis in combination with extrinsic pressure. Incomplete SVC obstruction is more often secondary to extrinsic pressure without thrombosis. Other causes include compression by intravascular arterial devices.

The incidence is on the rise, in line with the increased use of endovascular devices.

An obstructed SVC initiates collateral venous return to the heart from the upper half of the body through four principal pathways. The first and most important pathway is the azygous venous system, which includes the azygos vein, the hemiazygos vein, and the connecting intercostal veins. The second pathway is the internal mammary venous system plus tributaries and secondary communications to the superior and inferior epigastric veins. The long thoracic venous system, with its connections to the femoral veins and vertebral veins, provides the third and fourth collateral routes, respectively.

Despite these collateral pathways, venous pressure is almost always elevated in the upper compartment if obstruction of the SVC is present. Venous pressure as high as 200-500 cm H₂ O has been recorded in patients with severe SVCS.

Presentation

Superior Venecaval Syndrome

By Dr Deepu
Images
Definition
History
Pathophysiology
Presentation and Findings
Causes
Diagnostic Workup
Management

Definition

Superior vena cava syndrome (SVCS) is obstruction of blood flow through the superior vena cava (SVC). It is a medical emergency and most often manifests in patients with a malignant disease process within the thorax. A patient with SVCS requires immediate diagnostic evaluation and therapy.

History

William Hunter first described the syndrome in 1757 in a patient with syphilitic aortic aneurysm.

  In 1954, Schechter reviewed 274 well-documented cases of SVCS reported in the literature; 40% of them were due to syphilitic aneurysms or tuberculous mediastinitis.

Since the early reports, these infections have gradually decreased as the primary cause of SVC obstruction. Lung cancer, particularly adenocarcinoma, is now the underlying process in approximately 70% of patients with SVCS. However, as many as 40% of cases are attributable to nonmalignant causes.

Pathophysiology

Hospitals Considering Adding More Copper Surfaces That Can Help Kill Bacteria

By Dr Deepu

The Washington Post (9/20, Sun) reported at least 15 hospitals across the country have installed, or are considering installing, copper components on surfaces like light switches and door handles that are easily contaminated with microbes because of copper’s ability to “kill or inactivate a variety of pathogens by interacting with oxygen and modifying oxygen molecules.” Lynch, medical director of infection control at Harborview Medical Center in Seattle, said, “We’ve known for a long time that copper and other metals are effective in killing microbes, so it wasn’t a great leap to incorporate copper surfaces into hospitals.” The only published clinical trial showing how copper reduces infections in hospitals suggested copper surfaces reduced infection by 58 percent. The CDC is now seeking more research on the subject.