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November 9, 2009
Coding for Cerebral Infarction
For The Record
Vol. 21 No. 21 P. 24
A cerebral infarction (ICD-9-CM code 434.91), also called a stroke or cerebrovascular accident (CVA), occurs when the blood supply to a part of the brain is slowed or interrupted and brain tissue is deprived of oxygen and nutrients, causing cells to die. Major risk factors include hypertension, smoking, and elevated cholesterol levels, but prompt treatment can decrease the complications and damage.
There are two major types of stroke: ischemic and hemorrhagic. (Code assignment may change based on stroke type.) During an ischemic stroke, not enough blood reaches the brain because arteries are blocked or narrowed. Common ischemic strokes include thrombotic stroke (434.01), or the formation of a blood clot in an artery that supplies blood to the brain, and embolic stroke (434.11), which occurs when the blood clot breaks off and travels through the bloodstream to a vessel that feeds the brain. Atrial fibrillation is a common cause of embolic strokes.
If the CVA is caused by an occlusion, narrowing, or stenosis of a precerebral artery, a code from category 433 is assigned. Common precerebral arteries include the basilar, carotid, and vertebral. The fifth digit of 1 is assigned to show that the occlusion/stenosis caused the CVA. The physician must document that the stroke occurred as a result of the occlusion or stenosis before the fifth digit of 1 can be assigned. The infarction is of the artery specified and for the current episode of care (AHA Coding Clinic for ICD-9-CM, 1995, second quarter, pages 14-15).
A hemorrhagic stroke occurs when a blood vessel in the brain leaks or ruptures. Common types include intracerebral (431), subarachnoid (430), extradural/epidural (432.0), and subdural hemorrhages (432.1).
Common stroke symptoms include the loss of balance or coordination; dizziness; slurred speech; aphasia; paralysis, numbness, or weakness on one side of the body; blurred, double, or blackened vision; and sudden, severe headache.
It is appropriate to code residuals from a new CVA when the residual is still present at the time of discharge (AHA Coding Clinic for ICD-9-CM, 1989, second quarter, page 8).
A transient ischemic attack (TIA) is a temporary interruption of the blood flow to the brain. The signs and symptoms are the same as a stroke but last for a shorter period of time, usually minutes to 24 hours, with no residual effects. Because it is difficult to decipher whether someone is experiencing a TIA or a CVA, the physician’s initial impression may well be TIA vs. CVA. For a CVA/infarct, the coder should review the medical record for neurological deficits lasting longer than 24 hours, a CT scan showing a new area of infarction or hemorrhage, and a discharge order to rehabilitation where there is no other rationale for rehab. Final code assignment is based on physician documentation, so if there is conflicting or vague documentation, query the physician for clarification. TIA defaults to code 435.9. If the physician links a patient’s TIA to a specific precerebral artery, assign the more specific diagnosis code (eg, 433.10, TIA due to carotid stenosis).
Reversible ischemic neurologic deficit (RIND) describes a CVA in which deficits such as hemiplegia, dysphagia, and slurred speech last longer than those associated with a TIA and may persist for as long as six months but will eventually resolve. A RIND may show up as a slight perfusion defect on a perfusion MRI but may not be evident at all on most imaging studies. RIND is classified to code 434.91.
Treatment for an ischemic stroke involves clot-busting drugs such as tissue plasminogen activator (tPA). tPA (99.10) needs to be administered within three hours of symptom onset. Since tPA is contraindicated in hemorrhagic strokes, a CT scan is done immediately to rule it out. tPA may significantly improve symptoms, causing the physician to document “aborted CVA.” According to coding directives, an aborted CVA is assigned to code 434.91.
Since tPA must be administered quickly, it is usually given at a community hospital emergency department (ED). The patient is then transferred to a larger facility’s stroke center, which can provide the level of services required by the increased severity of these cases. So the facility providing the tPA administration in its ED doesn’t receive increased diagnosis-related group (DRG) reimbursement because the patient is transferred before being admitted. The receiving facility is not allowed to receive reimbursement for the tPA because it was administered at another facility. Code V45.88 is assigned as a secondary diagnosis in this instance to identify whether a patient received tPA prior to admission to the receiving facility. At this time, code V45.88 does not affect Medicare-severity DRG assignment, but it is important to capture as a secondary diagnosis when appropriate.
Strokes can also be treated surgically with carotid endarterectomy (38.12), angioplasty and stents (00.62 and 00.65 or 00.61 and 00.63/00.64), aneurysm clipping (39.51), or coiling, or aneurysm embolizations (39.72, 39.75, or 39.76).
Coding and sequencing for cerebral infarction are dependent on the physician documentation in the medical record and application of the Official Coding Guidelines for inpatient care. Also, use specific AHA Coding Clinic for ICD-9-CM and American Medical Association CPT Assistant references to ensure complete and accurate coding.
— This information was prepared by Audrey Howard, RHIA, of 3M Consulting Services. 3M Consulting Services is a business of 3M Health Information Systems, a supplier of coding and classification systems to more than 4,000 healthcare providers. The company and its representatives do not assume any responsibility for reimbursement decisions or claims denials made by providers or payers as the result of the misuse of this coding information. More information about 3M Health Information Systems is available at www.3mhis.com or by calling 800-367-2447. | 0 | 4 | 4 | 0 | 0 | 0 | 4 | 0.853533 | 4 | 1,398 |
Last month, we discussed OB/GYN coding as part of our ICD-10 Quick Tips blog series. This week, we will continue our discussion of OB/GYN coding and focus on coding of multiple gestations. In our past life (ICD-9!) we did not have too many options to capture this data, but ICD-10 certainly took care of that for us! We now have new coding concepts to address and apply, so let’s take a look at one of the biggest changes involving multiple gestation coding. Once again, I want to start with some basic information which is critical for understanding this concept of coding.
The first thing we must understand is the th ree different types of multiple gestations:
- Monoamniotic/monochromic (mo/mo): Mo/mo twins share the same amniotic sac and share the same placenta within the uterus. These multiples are always identical, but have two separate umbilical cords.
- Monoamniotic/diamniotic (mono/di): Mono/di twins generally have two amniotic sacs (a fetus in each sac) yet share the same placenta and have separate umbilical cords. These multiples are also identical.
- Dichorionic/diamniotic (di/di): This is the most common form of multiples. These type of twins usually have two amniotic sacs and two placentas. Di/di twins are commonly referred to as fraternal twins. This type of multiple rarely produces identicals.
To identify the fetus in a multiple gestation that is affected by the condition being coded. These are the applicable seventh characters:
- The seventh character 0 is for single gestations and multiple gestations where the affected fetus is unspecified.
- Seventh characters 1 through 9 are for cases of multiple gestations to identify the fetus for which the code applies.
- 0 – not applicable or unspecified (also used for single pregnancies)
- 1 – Fetus 1
- 2 – Fetus 2
- 3 – Fetus 3
- 4 – Fetus 4
- 5 – Fetus 5
- 9 – Other Fetus
- A code from category O30, Multiple gestation must also be assigned when assigning these codes
Therefore, if the physician is caring for a pregnant woman with the baby in breech presentation, you would report the appropriate seventh character from 1 through 9 to specify fetus 1, fetus 2, etc.
- For example - Mary, pregnant with twins, is close to her due date and the physician noticed that fetus 2 is in breech position. Report code 032.1xx2 (maternal care for breech presentation, fetus 2).
- Another example - Joan, pregnant with her first baby (single gestation), is ready to deliver but the baby is in breech position. Report 032.1xx0 (maternal care for breech presentation, not applicable).
Physicians often document twins as fetus A and fetus B. However, the fetal extensions in chapter 15, Pregnancy, childbirth and the puerperium, for codes related to complications of multiple gestation (e.g., O31, O32, etc.) refer to fetus 1, fetus 2, and so on. For the purposes of selecting the seventh character for these codes, it is appropriate to assume that fetus A is fetus 1 and B is 2, etc.
There you have it folks! Hope you found this short and sweet summary of coding multiple gestations in ICD-10! | 0 | 4 | 7 | 0 | 0 | 0 | 2 | 0.692129 | 2 | 735 |
Hearing loss: perceptions and solutions; Hearing loss can be dealt with effectively to improve a resident's quality of life.
Communication difficulties are not the only problems associated with hearing impairment. Hearing loss can lead to depression, social isolation, stress, and functional problems, such as impaired balance. Hearing loss and dementia have several symptoms in common, such as confusion, withdrawal, irritability, disorientation, and inappropriate responses, that can lead to a diagnosis of a more severe cognitive impairment than is truly the case. When furnished with hearing amplification, residents with dementia score better on cognitive screening tests than those without amplification. (3) When a proper screening program is in place and assistive listening devices are used, continuing decreases in quality of life and functional abilities can be stabilized.
Although there is no universal protocol for screening hearing in nursing home residents, helpful assessment tools do exist. The Hearing Handicap Inventory for the Elderly is a widely used screening questionnaire. This 10-item questionnaire assesses the emotional and social impacts of hearing loss on residents. Answers are given in a "Yes," "No," or "Sometimes" format and then scored accordingly. Scoring and interpretation instructions are provided (see table).
If a resident fails the screening, a full audiologic evaluation performed by a state-licensed, American Speech-Language-Hearing Association (ASHA)--certified audiologist is recommended. A comprehensive audiologic exam is considered the standard method for determining the type and severity of hearing loss and to rule out middle-ear pathology. In addition, it provides essential information in determining candidacy for hearing aids, assistive listening devices (ALDs), and aural rehabilitation. Medicare Part B covers hearing evaluations (CPT code 92557) when they are deemed medically necessary, such as to rule out a middle-ear pathology as a cause for a decrease in hearing.
Otoscopic ear examination should be performed in conjunction with an audio-logic evaluation to exclude other treatable causes of hearing loss, including cerumen (earwax) impaction, ear infections, and tympanic membrane perforations. In fact, cerumen impaction is one of the most common causes of hearing loss in the elderly and can be attributed to a hearing loss of up to 40 decibels. (4) Aural rehabilitation and amplification should be offered to residents once they have been qualified as candidates for these services.
Aural rehabilitation must be deemed medically necessary to be a covered service under Medicare. Medical necessity is determined by the recommendations of an audiologist and speech-language pathologist, and depends on determination that a hearing aid or an ALD in itself would not "sufficiently meet the patient's functional communication needs." (5) This type of speech-language therapy is reimbursable under CPT code 92507 which, under Medicare, is described as the "treatment of speech, language, voice communication, and/or auditory processing disorder."
Hearing aids are the most commonly used amplification for the hearing-impaired. It has been reported, however, that only one-fifth of all residents who could benefit from hearing aids actually own them. (6) The most common reasons cited for this are residents' anxiety about hearing aid maintenance and care, and cost. Other issues with hearing aids, such as problems with insertion, cleaning, changing batteries, using volume controls accurately, and turning hearing aids on and off, can indeed be overwhelming, and residents may decide that their hearing "isn't that bad" after all.
According to ConsumerAffairs.com, the average cost of a pair of hearing aids in 2004 was $2,300. (7) Cost can be prohibitive for the elderly, who might rely strictly on Medicare and Medigap to meet their healthcare needs. In fact, of the 10 standard Medigap plans available, not one covers the cost of hearing aids. A few commercial insurance companies reimburse for hearing aids, but coverage varies greatly. Medicaid coverage for hearing aids also varies greatly, depending on the state.
Other Amplification Options
Assistive technology can play an important role in the hearing healthcare of residents who are unable to handle or afford hearing aids. Assistive technology falls into two main categories: alerting devices and ALDs.
Alerting devices can help the hearing-impaired perceive environmental sounds, such as those made by a doorbell, telephone, or fire alarm. These devices rely typically on flashing lights or vibration to communicate. They provide an important service to those who want to maintain their independence and still ensure their safety.
ALDs help to address communication problems by amplifying sounds and are typically stand-alone devices; i.e., no hearing aids are required. There are many ALD options available, including telephone amplifying devices, TV listening systems, and personal listening systems.
Amplified telephones increase the volume of sound emanating from a telephone handset. These generally have adjustable volume and tone controls for personal listening preference and to help make it easier to hear difficult voices (i.e., women's and children's voices); they are usually hearing aid--compatible. Special amplifying devices are available that can be attached to an existing telephone to serve the same purpose.
TV listening systems typically use infrared technology to send sound from a transmitter plugged into the television to a headset receiver with an independent volume control. (It's no wonder that they are commonly referred to as "marriage savers.")
Personal listening systems are perhaps the most useful to nursing home residents. These systems are inexpensive compared with hearing aids and can be much easier to handle. Personal amplifiers are handheld, battery-operated devices that are perfect for one-on-one conversation or even watching television. Most personal amplifiers are hardwired, meaning that a microphone is attached to a receiver by a wire. An example of a personal amplifier is the Pocketalker Pro by Williams Sound. It comes with several headset options, a carrying case, and a microphone extension cord for a television. It operates on two AA batteries (with optional recharger) and comes standard with a five-year warranty.
There are times, however, when the resident or facility needs a less expensive option. In our practice, we recommend the Turbo Ear to fill this need. The Turbo Ear comes standard with in-the-ear headphones (other options may be available) and uses one AAA battery. The Turbo Ear does not provide as much amplification as the Pocketalker, but it can be quite helpful when trying to communicate with a hearing-impaired resident who has budget constraints.
Other personal amplifying systems are available. An audiologist should be consulted to help select the most appropriate device for the individual patient.
Hearing loss affects every aspect of a resident's life. It can greatly deteriorate quality of life and have a negative impact on independence. Nursing homes and long-term care facilities can help improve their resident's lives by using the specialized skills of speech-language pathologists and audiologists. Hearing impairment can easily be identified with a well-implemented screening process and improved with the help of an aural rehabilitation program that employs the use of assistive technology.
Amanda D. Nichols is Business Manager for Southeastern Hearing Services, a private audiology practice based in Tuscaloosa, Alabama. Its clients include more than 100 nursing homes in Alabama, Mississippi, and Arkansas. For further information, phone (205) 391-9876 or visit www.forhearing.com.
To send your comments to the author and editors, e-mail [email protected].
Note: The author's mention of specific products in this article should not be taken as an endorsement by Nursing Homes/Long Term Care Management.
1. Cruikshanks KJ, Wiley TL, Tweed TS, et al. Prevalence of hearing loss in older adults in Beaver Dam, Wisconsin. The Epidemiology of Hearing Loss Study. American Journal of Epidemiology 1998;148:879-86.
2. JonesA. The National Nursing Home Survey: 1999 summary. National Center for Health Statistics, Centers for Disease Control and Prevention, Department of Health and Human Services. Vital and Health Statistics 2002;13(152). Available at: www.cdc.gov/nchs/data/series/sr_13/sr13_152.pdf.
3. Weinstein BE, Amsel L. Hearing loss and senile dementia in the institutionalized elderly. Clinical Gerontologist 1986;4:3-15.
4. Lewis-Cullinan C, Janken JK. Effect of cerumen removal on the hearing ability of geriatric patients. Journal of Advanced Nursing 1990;15:594-600.
5. CMS Manual System: Pub 100-02 Medicare Benefit Policy, Transmittal 36, Change Request 3648. Centers for Medicare & Medicaid Services, Department of Health and Human Services. June 24, 2005. Available at: www.cms.gov/Transmittals/downloads/R36BP.pdf.
6. Popelka MM, Cruickshanks KJ, Wiley TL, et al. Low prevalence of hearing aid use among older adults with hearing loss: The Epidemiology of Hearing Loss Study. Journal of the American Geriatrics Society. 1998;46:1075-8.
7. Allen J. Hearing aids becoming easier & cheaper to buy. ConsumerAffairs.com; June 18, 2004. Available at: www.consumeraffairs.com/health/hearing/hearing_aids_01.html.
American Speech-Language-Hearing Association, www.asha.org
Better Hearing Institute, www.betterhearing.org
Centers for Medicare & Medicaid Services, www.cms.hhs.gov
HITEC Group, Ltd., www.hitec.com
Williams Sound Corp., www.willisamssound.com
Table. Hearing Handicap Inventory for the Elderly--Short Version. Instructions: Answer Yes, No, or Sometimes for each question. Do not skip a question if you avoid a situation because of hearing problems. If you use hearing aids or assistive devices, answer according to the way you hear without amplification. Scoring: No = 0; Sometimes = 2; Yes = 4. Interpretation of Scoring: 0-8 = no handicap; 10-24 = mild to moderate handicap; 26-40 = severe handicap. 1. Does a hearing problem cause you to feel embarrassed when you meet new people? 2. Does a hearing problem cause you to feel frustrated when talking to members of your family? 3. Do you have difficulty hearing when someone speaks in a whisper? 4. Do you feel handicapped by a hearing impairment? 5. Does a hearing problem cause you difficulty when visiting friends, relatives, or neighbors? 6. Does a hearing problem cause you to attend religious services less often than you would like? 7. Does a hearing problem cause you to have arguments with family members? 8. Does a hearing problem cause you difficulty when listening to TV or radio? 9. Do you feel that any difficulty with your hearing limits or hampers your personal or social life? 10. Does a hearing problem cause you difficulty when in a restaurant with relatives or friends? Source: Ventry IM, Weinstein BE. Identification of elderly people with hearing problems. American Speech-Language-Hearing Association 1983;25:37-42.
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What is ICD-10?
ICD-10 is the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD), a medical classification by the WHO. ICD-10 codes hold critical information about abnormal findings, complaints, diseases, epidemiology, external causes of injury, managing health, treating conditions, signs and symptoms, and social circumstances. There are more than 14,400 different codes in ICD-10 which can be further expanded to over 16,000 codes by using optional sub-classifications.
The U.S. Department of Health & Human Services (HHS) has designated ICD-10 as a code set under the Health Insurance Portability & Accountability Act (HIPAA) and it will be required for use by physicians and others in the health care industry beginning October 1, 2015. It will replace all ICD-9 code sets. Thus, for any healthcare service that occurs on or after October 1, 2015, providers must use ICD-10 codes. This mandate applies to healthcare reimbursement, research, and reporting services. CMS has stated that they will offer no grace period and no additional delays for the transition.
Benefits of ICD-10
The U.S. has been using ICD-9 since 1979, and it is not sufficiently robust to serve the healthcare needs of the future. The content has limited data about patients’ medical conditions and hospital inpatient procedures, the number of available codes is limited, and the coding structure is too restrictive. Most developed countries have already made the transition to ICD-10 code sets, so the U.S. cannot compare U.S. morbidity diagnosis data at the international level.
ICD-10 code sets will enhance the quality of data for:
- Tracking public health conditions (complications, anatomical location)
- Improved data for epidemiological research (severity of illness, co-morbidities)
- Measuring outcomes and care provided to patients
- Making clinical decisions
- Identifying fraud and abuse
- Designing payment systems/processing claims
Through expanded categories and diagnosis codes, ICD-10 will foster a more accurate reporting system that will result in better clinical decision support. It also provides better data for measuring and tracking health care utilization and the quality of patient care. The granularity of ICD-10-is vastly improved over ICD-9 and will enable greater specificity in identifying health conditions.
- The greater level of detail in the new code sets includes laterality, severity, and complexity of disease conditions, which will enable more precise identification and tracking of specific conditions.
- Revised terminology and disease classification to be more consistent with new technology and current clinical practice.
- Injuries, poisonings and external causes are much more detailed in ICD-10-CM. The codes include the severity of injuries, and how and where injuries happened. Extensions are also used to provide additional information for many injury codes.
- Pregnancy trimester is designated for ICD-10-CM codes in the pregnancy, delivery and puerperium chapter.
- Postoperative codes are expanded and now distinguish between intraoperative and post-procedural complications.
- There are new concepts that did not exist in ICD-9-CM, such as under dosing, blood type, the Glasgow Coma Scale, and alcohol level.
Key differences between ICD-9 and ICD-10 codes
|Comparison of Diagnosis Code Sets|
|3-5 Characters in length||3-7 Characters in length|
|First character may be alpha or numeric, characters 2-5 are numeric||Character 1 is alpha; Characters 2 and 3 are numeric; characters 4-7 are alpha or numeric|
|Less specificity||Greater specificity|
|Laterality not specified||Laterality specified (e.g. left versus right)|
|Limited space for new codes||Flexibility to add new codes|
|ICD-10-CM Code Structure|
|Characters 1 through 3 – Category|
|Characters 4 through 6 – Etiology, anatomic site, severity, or other clinical detail|
|Character 7 – Extension|
|ICD-10-CM Code Detail|
|S52 Fracture of the forearm|
|S52.3 Fracture of the shaft of the radius|
|S52.32 Transverse fracture of the shaft of the radius|
|S52.321 Displaced transverse fracture of the shaft of the right radius|
|S52.321A Displaced transverse fracture of the shaft of the right radius,initial encounter for closed fracture|
How to prepare for ICD-10
The transition to ICD-10 is expected to be much more disruptive for physicians than previous HIPAA mandates, as they must adjust their documentation and other processes. Unlike previous HIPAA mandates where physicians could lean heavily on other partners, such as billing services, vendors, and clearinghouses, use of the new codes will require a much deeper level of involvement by the physicians themselves. | 0 | 4 | 6 | 0 | 0 | 0 | 2 | 0.676347 | 2 | 1,044 |
5 Common Causes and ICD 10 Code of Palpitations
If you feel like your heart is beating too fast or too hard, skipping a beat or even fluttering, you have palpitations. ICD-10 code for palpitations is R00. ICD is known as the standard diagnostic tool which is used in clinical care and research to define diseases. It includes monitoring of the incidence and prevalence of diseases. The ICD-10 code for palpitations is in Chapter 18, Section R00-R09.
You can check your heart palpitations in your chest, throat or neck. Palpitation occurs by certain condition that is usually not serious or harmful. In rare cases, the fast heart beat can be a sign of a more serious heart condition too. Some common reasons why a person experience heart palpitations can include the following.
- Anxiety and Stress
Normally, when a person is stressed out or nervous, his brain releases hormones which can cause the heart to pound. So, it is clear that being anxious or stressed can bring about heart palpitations. Another strong emotion such as fear can absolutely trigger palpitations too.
People often ignore the amount of fluids that their bodies need. Losing too much fluids or nor drinking enough fluid can lead to severe dehydration. In fact, dehydration can lower your blood pressure. This can bring you to experience palpitations.
- Strenuous Physical Activity
A person who engages in strenuous physical activity may experience heart palpitations after or before the exercise but they are rare during the workout. Your heart rate increases during physical activity but the palpitations diminish. In contrast, the palpitations may return once the workout is done and the heart slows down gradually.
- Stimulants Like Caffeine
Caffeine is one of stimulants that can affect your heart if you consuming it too much or having it at the wrong time. It is can affect your brain and muscles as well. Other stimulants such as nicotine, alcohol, illegal street drugs can lead you to have palpitations too.
- Certain Meals
Something that we eat always creates an effect, either good or bad. Consuming heavy meals which are high in fats or sugar are though as triggers to palpitations. Others believe that foods with high levels of nitrates or sodium are also the triggers. In this case, it is about all about food sensitivities. So, it may be not same between one another. It is better for you to identify your food sensitivity. | 0 | 3 | 2 | 0 | 0 | 0 | 4 | 0.988205 | 4 | 519 |
What the Anesthesiologist Should Know before the Operative Procedure
During uterine curettage, an instrument is used to scrape or suction the uterine lining to diagnose and/or treat abnormal bleeding or to remove products of conception. If not already dilated, the cervix must first be opened mechanically or chemically.
The indication for the dilation and curettage is an important concern for the anesthesiologist. An acute hemorrhage situation requiring an emergent or urgent dilation and curettage requires additional setup and has higher risks, while a diagnostic elective procedure typically has lower risks. Therefore, it is important for the anesthesiologist to know the indication for the procedure.
The complications associated with this procedure, which consist primarily of bleeding and uterine perforation, occur at a frequency of approximately 1-2%. In order to maximize the diagnostic and therapeutic yield and minimize risk, Dilation and Curettage (D & C) or Dilation and Evacuation (D & E) can be substituted by non-invasive procedures (such as transvaginal ultrasound) when appropriate, or augmented with more directed techniques, such as hysteroscopy and/or polypectomy.
The causes of uterine bleeding leading to curettage include:
1) Pregnancy-related issues, such as miscarriage, retained products of conception, or therapeutic abortion.
2) Non-pregnancy-related issues, such as investigation of fibroids or polyps or hyperplastic uterine linings.
1. What is the urgency of the surgery?
What is the risk of delay in order to obtain additional preoperative information?
D & Cs or D & Es are elective, outpatient procedures if there is no major bleeding and/or if the procedure is done for diagnostic purposes.
Emergent: If the patient is having active and ongoing bleeding resulting in subjective symptoms, such as lightheadedness or palpitations, or is showing objective signs of significant hypovolemia, such as hypotension or tachycardia, then the D & C should be performed as soon as possible. Delaying curettage may result in exsanguination. Practitioners should be prepared for major resuscitation that includes crystalloids, colloids, and blood products (in some cases, uncrossed-matched RBCs) as needed. Depending on the source of bleeding, the procedure may need to be converted to a laparoscopy or laparotomy.
Urgent: Patients with chronic bleeding are often evaluated first by imaging (e.g. ultrasound) to inform the decision of whether or not to proceed with D & C. There is typically time for these patients to undergo a more thorough preoperative evaluation and for blood to be typed and crossed, if needed.
Elective: Patients with intermittent, abnormal vaginal bleeding, uterine fibroids, or polyps may undergo D & C as an elective procedure. These procedures are typically used to determine the cause of bleeding and, in some cases, the benign or malignant nature of a uterine growth. These patients can undergo pre-operative testing based on the presence or absence of co-morbidities.
2. Preoperative evaluation
During the preoperative evaluation, it is important to assess the pregnancy status of the patient, as dilatation and curettage is contraindicated in patient with a viable and desired intrauterine pregnancy.
Medically unstable conditions warranting further evaluation include major cardiac or pulmonary disease or clotting disorders. Patients with pelvic infections are at risk for bacteremia and perforation as a result of the fragile uterine tissue.
In general, cardiac testing is unnecessary for asymptomatic patients. Delaying surgery may be indicated if the patient is pregnant and this is not a pregnancy-related D & C or if the procedure is elective and the patient is unstable because of comorbid illness. The patient should be optimized prior to proceeding with surgery, if feasible, if she had cardiac issues, such as unstable angina, and if significant intra-operative bleeding is expected.
Patients with severe hip arthritis can be difficult or impossible to position in stirrups (i.e. lithotomy), thus limiting the feasibility of these procedures.
Patients with pre-existing cardiac, gastrointestinal, or pulmonary issues may benefit from regional or paracervical blocks. It would be important to evaluate these patients preoperatively for coagulation disorders or infection near the block site.
3. What are the implications of co-existing disease on perioperative care?
Patients with acute or chronic bleeding should have a baseline CBC. If bleeding has been significant (>=1.5 liters acutely, or multiple recent bleeds), then consider a DIC screen.
b. Cardiovascular system
Acute ongoing hemorrhage may exacerbate underlying cardiac ischemia, further necessitating prompt resuscitation and identification of the underlying cause of bleeding.
Baseline coronary artery disease or cardiac dysfunction
Goals of management: If the patient’s pain and bleeding are well controlled, then the D & C or D & E should lead to minimal hemodynamic derangement. However, inadequate anesthesia and major hemorrhage can precipitate ischemia through increased utilization and decreased availability of oxygen.
Patients with a significant smoking history, chronic bronchitis, or baseline oxygen requirements should be identified preoperatively. Patients with acute or chronic alcohol use can have increased risk for aspiration and more colonization with pathologic bacteria in their airway. Unless an acute COPD exacerbation is suspected, additional preoperative testing is rarely indicated.
Perioperative Risk Reduction Strategies
These targeted patients should continue their ongoing medication regimens, assuming they are optimized. Patients with COPD may benefit from short term preoperative inhaled or systemic corticosteroids. Anesthetic techniques that avoid instrumenting the airway, such as a paracervical block with sedation or neuraxial anesthetics, are preferable to general anesthesia. Patients with a history of smoking or excessive alcohol consumption should be advised to practice smoking and alcohol cessation at least 4-8 weeks prior to surgery.
Reactive Airway Disease (i.e., Asthma)
The status and severity of the patient’s disease should be assessed, including identifying common triggers, the response to bronchodilators, history of recent hospitalizations, prior steroid therapy, or intubations for exacerbations.
Perioperative Risk Reduction Strategies
Ideally, patients would not undergo a procedure during an asthma or COPD exacerbation, but rather they would first be medically optimized. If the procedure is emergent, the anesthetic technique of choice would be to allow the patient to breathe spontaneously and avoid instrumentation of the airway (e.g. paracervical block with sedation/MAC or spinal). If general anesthesia is necessary, then initial use of a volatile agent to aid in bronchodilation, decreased to 0.5 MAC after induction to promote uterine contraction post-procedure, would be beneficial. Preoperative and intraoperative treatment with inhaled bronchodilator therapy may also benefit these patients. In situations with excessive bleeding, carboprost (Hemabate) should be avoided or used cautiously as it can cause bronchospasm in susceptible individuals. Alternative uterotonic agents such as oxytocin, methergine, or misoprostol should be used instead.
Active respiratory therapy is advisable.
As per ASA guidelines, patients undergoing non-urgent or emergent D & C should be NPO for 6-8 hours for solid food and 2 hours for clear liquids prior to the procedure. Those with symptomatic reflux should be identified, and should undergo light sedation that preserves airway reflexes (+ paracervical block or neuraxial anesthetic) or rapid sequence induction with general endotracheal anesthesia after H2 blocker therapy.
g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (e.g., musculoskeletal in orthopedic procedures, hematologic in a cancer patient)
Patients with a history of or active cervical or uterine cancer should be evaluated preoperatively and managed carefully as heavy bleeding or perforation can occur. The anesthesiologist should be prepared with proper IV access and blood products on standby.
4. What are the patient's medications and how should they be managed in the perioperative period?
h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern?
If patients are taking anti-coagulants or anti-platelet agents, they should consult with their physicians at least a week prior to surgery for further instructions, as some of these medications have an extremely long half-life.
i. What should be recommended with regard to continuation of medications taken chronically?
consult with multidisciplinary team
j. How To modify care for patients with known allergies –
k. Latex allergy- If the patient has a sensitivity to latex (e.g., rash from gloves, underwear.) versus anaphylactic reaction, prepare the operating room with latex-free products.
In case of anaphylaxis, epinephrine, IV H1, H2 blockers and steroids, and rescue airway equipment should be readily available.
Diagnostic dilation and curettage (Endometrial biopsy): No antibiotics
Elective suction curettage abortion: Antibiotic prophylaxis is indicated. Optimal antibiotic agents and dosages vary. One of the most effective and least expensive regimens is Doxycycline.
l. Does the patient have any antibiotic allergies?
m. Does the patient have a history of allergy to anesthesia?
Malignant hyperthermia (MH)
Avoid all trigger agents, such as succinylcholine and inhalational agents.
Insure MH cart available: Clean machine according to individual anesthesia machine protocol. Use regional technique or paracervical block if possible.
These are not considered to be MH triggering agents, and therefore can be used in patients at risk for malignant hyperthermia. It is important to ask patients if they are allergic to local anesthetics or sunscreen containing PABA (relevant for ester local anesthetics) before administering local anesthetic.
5. What laboratory tests should be obtained and has everything been reviewed?
For young healthy patients not at risk of significant bleeding, no pre-operative labs are needed unless there is significant hemorrhage.
Intraoperative Management: What are the options for anesthetic management and how to determine the best technique?
The anesthetic options for dilation and curettage include conscious sedation or MAC (monitored anesthesia care) +/- paracervical block, neuraxial, and general anesthesia. The optimal anesthetic choice depends on the patient and:
a) the degree of hemorrhage/hemodynamic stability,
b) the patient and provider preference,
c) and cervical dilation, which may affect the feasibility of doing a paracervical block.
The Cochrane Database Review (2009) examined 17 studies, including over 1,855 participants, regarding cervical dilation and uterine intervention with paracervical block when compared with no treatment, placebo, and other regional anesthesia, systemic sedation, or GA. Some studies reported that women experienced severe pain (mean scores of 7-/10) during uterine intervention, irrespective of the analgesia technique used. No technique provided reliable pain control.
The available evidence fails to show whether paracervical block is inferior, equivalent to, or superior to alternative analgesia techniques in terms of efficacy and safety for women undergoing uterine interventions.
a. Regional anesthesia
Regional anesthesia, including Paracervical block (+/- sedation), +/- intrauterine local anesthetic and neuraxial (+/- sedation) have been reported for D & C and D & E.
Benefits: anecdotally, patients typically feel the least discomfort.
Drawbacks: low, but non-zero, risk of post-dural puncture headache (PDPH) and transient radicular irritation (TRI) in setting of outpatient procedure and lithotomy position. Consider using hyperbaric bupivacaine 0.75% (1-1.5 ccs) with fentanyl (10-20 mics) or, if less than 1 hour of procedure time is anticipated, mepivacaine 1.5% (45-60 mg) with preservative-free dextrose (approximately 1 cc) or chloroprocaine 40-60mg. Recovery time varies and the patient may have to recover in hospital before being discharged.
2. Peripheral Nerve Block
e.g., paracervical (consider Nesacaine 1%)
Benefits: less invasive and better analgesia than sedation alone.
Drawbacks: reports of pain regardless of the agent used if paracervical block is done without sedation.
Benefits: less invasive. Some investigations have shown that 5 cc’s of 2% lidocaine can be as effective as paracervical block or po NSAID. As with paracervical block, use in conjunction with conscious sedation for best results.
b. General Anesthesia
Benefits: secured airway, anecdotally more reliable pain management, and less intra-op patient movement.
Drawbacks: potential airway issues or increased risk of aspiration if patient is beyond the first trimester of pregnancy or recently post-partum. Increased risk of postoperative nausea and vomiting.
c. Monitored Anesthesia Care
D & C is often done under sedation or Monitored Anesthesia Care (MAC) with paracervical block.
There are many analgesia and anesthetic agents that can be used in bolus dosing or as continuous infusions (e.g., Fentanyl and Versed, Propofol and Remifentanil). In one randomized, controlled trial, propofol (target concentration of 5 mics/ml) was recommended for D & C when administered with Fentanyl 1 mic/kg and N02 (66%) as compared with 4 and 6 mics/cc. Close monitoring and appropriate respiratory management were deemed necessary for safe administration.
Benefits include that it takes the patient less time to wake up when compared with general anesthesia, potentially less need to instrument the airway, if the patient continues to breath spontaneously, and the avoidance of post-dural puncture headache.
Drawbacks include the risk of respiratory depression, which could lead to depressed airway reflexes, aspiration, and/or apnea, the potential for patient movement, increasing the chance of uterine perforation, and a greater chance of inadequate pain relief when compared to neuraxial or general anesthesia.
6. What is the author's preferred method of anesthesia technique and why?
When obstetric providers expect that the procedure will be straightforward (that is, there is no molar pregnancy or malplacentation) for first trimester incomplete or therapeutic abortions or the removal of retained products of conception, then our anesthetic of choice is a paracervical block placed by the surgeons (using 1% Nesacaine) and MAC. We use various combinations of anesthetics for sedation during the MAC, including bolus fentanyl and versed or propofol and remifentanil infusions.
For second trimester D & Es, our anesthetic of choice is typically either spinal or general (endotracheal) anesthesia, and occasionally MAC plus paracervical block The MAC with paracervical block option requires careful case selection (e.g., absence of symptomatic reflux in the patient, anticipation of a straightforward procedure).
If significant bleeding has occurred or is expected, or if the patient is hemodynamically unstable, then we proceed with resuscitation and general endotracheal anesthesia. If the uterus needs to be evacuated urgently, but the patient has recently ingested food other than clear liquids or has an active upper respiratory infection, we will proceed with a spinal anesthetic with light-to-moderate sedation if no contraindications, such as coagulopathy or hemodynamic instability, exist.
If there are no contraindications and no objections by the surgical team, interoperative ketorolac 30mg is given IV for postoperative pain control. Patients are continued on NSAIDs postoperatively on an as-needed basis for pain control.
What prophylactic antibiotics should be administered?
According to the ACOG guidelines, despite the lack of data, antibiotic prophylaxis is indicated for elective and missed suction curettage abortion. Although the optimal antibiotic regimen is unclear, Doxycycline (100 mg prior to the procedure and 200 mg post-procedure) was shown in a meta-analysis to be effective and inexpensive. In a prospective, randomized, controlled trial, antibiotic prophylaxis showed no benefit before the treatment of incomplete abortion.
What do I need to know about the surgical technique to optimize my anesthetic care?
Will there be manual dilation of the cervix?
In general, dilation is painful and requires a significant degree of anesthesia (i.e., a functional paracervical block, spinal, or general anesthesia).
Will this be a first or second trimester gestation?
In general, second trimester D & Es are more complex and are less conducive to MAC.
What can I do intraoperatively to assist the surgeon and optimize patient care?
During manual dilation of the cervix and active curettage, it is important that the patient not move her hips or lower extremities, as movement can increase the risk of uterine perforation. As such, the patient should either be conscious and able to control her own body or sedated enough to restrict movement (e.g., during a GET).
What are the most common intraoperative complications and how can they be avoided/treated?
Attention to pre-op volume status and intra-op bleeding is essential. In the case of straight-forward first trimester missed Ab, the bleeding is often self-limited. Patients with chronic uterine bleeding or retained products of conception requiring D & E can often require significant resuscitation, including blood products such as PRBCs, FFP, platelets, and Cryoprecipitate, if bleeding is severe.
As with any change in patient status, suspected uterine perforation should prompt direct and specific communication between the surgery, nursing, and anesthesia teams. Minor perforation can have little to no effect on the patient’s intra-op course, while major perforation can require urgent laparotomy and precipitate significant hemorrhage.
Uterine perforation is of higher likelihood in procedures done to treat uterine bleeding as opposed to diagnostic dilatation and curettage. Risk of perforation is also increased in pregnancy.
Amniotic Fluid Embolus (AFE) has been reported in pregnancy-related D & E. Therapy involves supportive care; in cases of cardiac or respiratory collapse, cardiopulmonary bypass or ECMO have been employed in some isolated cases. In general, morbidity and mortality is high with AFE.
Patients who have outpatient procedures in the lithotomy position under spinal anesthesia have an increased incidence of Transient Radicular Irritation (TRI).
b. If the patient is intubated, are there any special criteria for extubation?
If there has been significant hemorrhage and resuscitation, it is important to assess tissue swelling and airway swelling before extubation.
c. Postoperative management
What analgesic modalities can I implement?
If not otherwise contraindicated, NSAIDS (e.g., Toradol) +/- opioids are particularly useful for post-D & E pain management, given the high incidence of uterine cramping.
What level bed acuity is appropriate?
Unless there has been significant hemorrhage, D & E is often done as an outpatient procedure. Those patients who have required significant resuscitation may need to be in an inpatient setting overnight; in this case, the patient’s underlying health status and degree of hemodynamic stability post-procedure can be used to decide whether she needs a monitored bed (e.g. step-down Unit or ICU).
What are common postoperative complications, and ways to prevent and treat them?
To prevent post-operative bleeding, patients will sometimes be given intra-operative uterotonic agents as well as resuscitation with crystalloids or blood products as needed. Those with suspected uterine perforation are often treated with antibiotics. The development of TRI after spinal anesthetic is typically a relatively benign and self-limited event.
What's the Evidence?
“Antibiotic Prophylaxis for Gynecologic Procedures”. Obstetrics and Gynecology. vol. 113. 2009. pp. 1180-1189. (This document summarizes the recommendations for first and second line prophylaxis [including exclusion criteria] for D & E and other gynecologic procedures.)
Agostini, A, Provansal, M. “Comparison of ropivacaine and lidocaine for paracervical block during surgical abortion”. Contraception. vol. 77. 2008. pp. 382-385. (In this randomized, double-blind study, intraoperative pain was better, although still elevated, when ropivacaine was used for paracervical block compared with lidocaine. Postoperative pain was not different between the two groups.)
Api, O, Ergen, B. “Comparison of oral nonsteroidal analgesic and intrauterine local anesthetic for pain relief in uterine fractional curettage: a randomized, double-blind, placebo-controlled trial”. Am J Obstet Gynecol. vol. 203. 2010. pp. 28 e21-27. (Either intrauterine lidocaine (5 cc's 2% lidocaine) or oral dexketoprofen were effective in relieving fractional curettage-related pain, although a combination of the two medications did not demonstrate a clinically relevant increase in analgesia.)
Castillo, T, Avellanal, M. “Bolus application of remifentanil with propofol for dilatation and curettage”. Eur J Anaesthesiol. vol. 21. 2004. pp. 408-411. (The most favorable intra-op anesthetic conditions and post-operative recovery times were found with Remifentanil 1.5 mic/ kg(-1) i.v. with propofol 2 mg kg(-1) i.v. and 60% nitrous oxide in oxygen.)
Fox, M. C, Hayes, J. L.. “Cervical preparation for second-trimester surgical abortion prior to 20 weeks of gestation”. Contraception. vol. 76. 2007. pp. 486-495. (These clinical guidelines explore the role of cervical preparation for D & E prior to 20 weeks’ gestation, specifically addressing the available osmotic dilators.)
Mankowski, J. L, Kingston, J. “Paracervical compared with intracervical lidocaine for suction curettage: a randomized controlled trial”. Obstet Gynecol. vol. 113. 2009. pp. 1052-1057. (According to this investigation, either of these techniques, coupled with conscious sedation, provides effective and acceptable analgesia for first trimester suction curettage.)
Rattanachaiyanont, M, Leerasiri, P. “Effectiveness of intrauterine anesthesia for pain relief during fractional curettage”. Obstet Gynecol. vol. 106. 2005. pp. 533-539. (This randomized, double-blind, controlled study showed that the addition of intrauterine anesthesia (in this case 5ml 2%lidocaine in addition to the paracervical block) further reduced pain during D & C without increasing side effects.)
Sotiriadis, A, Makrydimas, G. “Expectant, medical, or surgical management of first-trimester miscarriage: a meta-analysis”. Obstet Gynecol. vol. 105. 2005. pp. 1104-1113. (Complete evacuation of the uterus was more common if surgical management was undertaken than if there was medical management of first trimester or incomplete miscarriage. Expectant management had very variable success rates.)
Tangsiriwatthana, T, Sangkomkamhang, U. S. “Paracervical local anaesthesia for cervical dilatation and uterine intervention”. Cochrane Database Syst Rev. 2009. pp. CD005056(The Cochrane Database Review (2009) examined 17 studies, including over 1,855 participants, regarding cervical dilation and uterine intervention with paracervical block when compared with no treatment, placebo, and other regional anesthesia, systemic sedation, or GA. Some studies reported that women experienced severe pain (mean scores of 7-/10) during uterine intervention, irrespective of the analgesia technique used. No technique provided reliable pain control.)
Tuncalp, O, Gulmezoglu, A. M. “Surgical procedures for evacuating incomplete miscarriage”. Cochrane Database Syst Rev. vol. 9. 2010. pp. CD001993(This paper indicates that serious complications (e.g. uterine perforation and other morbidity) were rare, but the trial sample sizes were not large enough to evaluate small or moderate differences.)
Uerpairojkit, K, Urusopone, P. “A randomized controlled study of three targets of propofol plasma concentration in patients undergoing uterine dilation and curettage”. J Obstet Gynaecol Res. vol. 29. 2003. pp. 79-83. (The authors conclude that a target propofol concentration of 5 mics/ml in conjunction with Fentanyl 1mic/kg and nitrous oxide 66% minimized patient movement, hypotension, and respiratory depression during D & C.)
Silvanus, MT, Groeben, H, Peters, J. “Corticosteroids and inhaled salbutamol in patients with reversible airway obstruction markedly decrease the incidence of bronchospasm after tracheal intubation”. Anesthesiology. vol. 100. 2004. pp. 1052-7.
Warner, MA, Offord, KP, Warner, ME, Lennon, RL, Conover, MA, Jansson-Schumacher, U. “Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients”. Mayo Clin Proc. vol. 64. 1989. pp. 609-616.
Nelson, G, Altman, AD, Nick, A, Meyer, LA. “Guidelines for pre- and intra-operative care in gynecologic/oncology surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations – Part I”. Gynecologic Oncology. vol. 140. 2016. pp. 313-322.
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- What the Anesthesiologist Should Know before the Operative Procedure
- 1. What is the urgency of the surgery?
- What is the risk of delay in order to obtain additional preoperative information?
- 2. Preoperative evaluation
- 3. What are the implications of co-existing disease on perioperative care?
- b. Cardiovascular system
- c. Pulmonary
- d. Renal-GI:
- e. Neurologic:
- f. Endocrine:
- g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (e.g., musculoskeletal in orthopedic procedures, hematologic in a cancer patient)
- 4. What are the patient's medications and how should they be managed in the perioperative period?
- h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern?
- i. What should be recommended with regard to continuation of medications taken chronically?
- j. How To modify care for patients with known allergies -
- k. Latex allergy- If the patient has a sensitivity to latex (e.g., rash from gloves, underwear.) versus anaphylactic reaction, prepare the operating room with latex-free products.
- l. Does the patient have any antibiotic allergies?
- m. Does the patient have a history of allergy to anesthesia?
- 5. What laboratory tests should be obtained and has everything been reviewed?
- Intraoperative Management: What are the options for anesthetic management and how to determine the best technique?
- 6. What is the author's preferred method of anesthesia technique and why?
- What prophylactic antibiotics should be administered?
- What do I need to know about the surgical technique to optimize my anesthetic care?
- Will there be manual dilation of the cervix?
- Will this be a first or second trimester gestation?
- What can I do intraoperatively to assist the surgeon and optimize patient care?
- What are the most common intraoperative complications and how can they be avoided/treated?
- Uterine Perforation
- Cardiac/Pulmonary Complications
- a. Neurologic
- b. If the patient is intubated, are there any special criteria for extubation?
- c. Postoperative management | 0 | 2 | 10 | 0 | 0 | 0 | 1 | 0.753257 | 1 | 6,297 |
Pulmonary edema is fluid accumulation in the tissue and air spaces of the lungs. It leads to impaired gas exchange and may cause respiratory failure. It is due to either failure of the left ventricle of the heart to remove blood adequately from the pulmonary circulation (cardiogenic pulmonary edema), or an injury to the lung parenchyma or vasculature of the lung (noncardiogenic pulmonary edema). Treatment is focused on three aspects: firstly improving respiratory function, secondly, treating the underlying cause, and thirdly avoiding further damage to the lung. Pulmonary edema, especially acute, can lead to fatal respiratory distress or cardiac arrest due to hypoxia. It is a cardinal feature of congestive heart failure. The term edema is from the Greek οἴδημα (oídēma, "swelling"), from οἰδέω (oidéō, "I swell").
|Pulmonary edema with small pleural effusions on both sides.|
|Classification and external resources|
|Specialty||Cardiology, critical care medicine|
|eMedicine||article/157452 article/300813, article/360932|
Signs and symptomsEdit
The most common symptom of pulmonary edema is difficulty breathing, but may include other symptoms such as coughing up blood (classically seen as pink, frothy sputum), excessive sweating, anxiety, and pale skin. Shortness of breath can manifest as orthopnea (inability to lie down flat due to breathlessness) and/or paroxysmal nocturnal dyspnea (episodes of severe sudden breathlessness at night). These are common presenting symptoms of chronic pulmonary edema due to left ventricular failure. The development of pulmonary edema may be associated with symptoms and signs of "fluid overload"; this is a non-specific term to describe the manifestations of left ventricular failure on the rest of the body and includes peripheral edema (swelling of the legs, in general, of the "pitting" variety, wherein the skin is slow to return to normal when pressed upon), raised jugular venous pressure and hepatomegaly, where the liver is enlarged and may be tender or even pulsatile. Other signs include end-inspiratory crackles (sounds heard at the end of a deep breath) on auscultation and the presence of a third heart sound.
Classically it is cardiogenic (left ventricular) but fluid may also accumulate due to damage to the lung. This damage may be direct injury or injury mediated by high pressures within the pulmonary circulation. When directly or indirectly caused by increased left ventricular pressure pulmonary edema may form when mean pulmonary pressure rises from the normal of 15 mmHg to above 25 mmHg. Broadly, the causes of pulmonary edema can be divided into cardiogenic and non-cardiogenic. By convention cardiogenic refers to left ventricular causes.
- Congestive heart failure which is due to the heart's inability to pump the blood out of the pulmonary circulation at a sufficient rate resulting in elevation in wedge pressure and pulmonary edema – this may be due to left ventricular failure, arrhythmias, or fluid overload, e.g., from kidney failure or intravenous therapy.
- Hypertensive crisis can cause pulmonary edema as the elevation in blood pressure and increased afterload on the left ventricle hinders forward flow and causes the elevation in wedge pressure and subsequent pulmonary edema.
- Negative pressure pulmonary edema in which a significant negative pressure in the chest (such as from an inhalation against an upper airway obstruction) ruptures capillaries and floods the alveoli.
- Neurogenic causes (seizures, head trauma, strangulation, electrocution).
- Acute respiratory distress syndrome
Injury to the lung may also cause pulmonary edema through injury to the vasculature and parenchyma of the lung. The acute lung injury-acute respiratory distress syndrome (ALI-ARDS) covers many of these causes, but they may include:
- Inhalation of hot or toxic gases
- Pulmonary contusion, i.e., high-energy trauma (e.g. vehicle accidents)
- Aspiration, e.g., gastric fluid
- Reexpansion, i.e. post large volume thoracocentesis, resolution of pneumothorax, post decortication, removal of endobronchial obstruction, effectively a form of negative pressure pulmonary oedema.
- Reperfusion injury, i.e. postpulmonary thromboendartectomy or lung transplantation
- Swimming induced pulmonary edema also known as immersion pulmonary edema
- Transfusion Associated Circulatory Overload (TACO) occurs when multiple blood transfusions or blood-products (plasma, platelets, etc.) are transfused over a short period of time.
- Transfusion associated Acute Lung Injury (TRALI) is a specific type of blood-product transfusion injury that occurs when the donors plasma contained antibodies against the donor, such as anti-HLA or anti-neutrophil antibodies.
- Severe infection or inflammation which may be local or systemic. This is the classical form of ALI-ARDS.
Some causes of pulmonary edema are less well characterised and arguably represent specific instances of the broader classifications above.
Flash pulmonary edemaEdit
Flash pulmonary edema (FPE), is rapid onset pulmonary edema. It is most often precipitated by acute myocardial infarction or mitral regurgitation, but can be caused by aortic regurgitation, heart failure, or almost any cause of elevated left ventricular filling pressures. Treatment of FPE should be directed at the underlying cause, but the mainstays are ensuring adequate oxygenation, diuresis, and decrease of pulmonary circulation pressures.
Recurrence of FPE is thought to be associated with hypertension and may signify renal artery stenosis. Prevention of recurrence is based on managing hypertension, coronary artery disease, renovascular hypertension, and heart failure.
There is no one single test for confirming that breathlessness is caused by pulmonary edema; indeed, in many cases, the cause of shortness of breath is probably multifactorial.
Low oxygen saturation and disturbed arterial blood gas readings support the proposed diagnosis by suggesting a pulmonary shunt. Chest X-ray will show fluid in the alveolar walls, Kerley B lines, increased vascular shadowing in a classical batwing peri-hilum pattern, upper lobe diversion (increased blood flow to the superior parts of the lung), and possibly pleural effusions. In contrast, patchy alveolar infiltrates are more typically associated with noncardiogenic edema
Lung ultrasound, employed by a healthcare provider at the point of care, is also a useful tool to diagnose pulmonary edema; not only is it accurate, but it may quantify the degree of lung water, track changes over time, and differentiate between cardiogenic and non-cardiogenic edema.
Especially in the case of cardiogenic pulmonary edema, urgent echocardiography may strengthen the diagnosis by demonstrating impaired left ventricular function, high central venous pressures and high pulmonary artery pressures.
Blood tests are performed for electrolytes (sodium, potassium) and markers of renal function (creatinine, urea). Liver enzymes, inflammatory markers (usually C-reactive protein) and a complete blood count as well as coagulation studies (PT, aPTT) are also typically requested. B-type natriuretic peptide (BNP) is available in many hospitals, sometimes even as a point-of-care test. Low levels of BNP (<100 pg/ml) suggest a cardiac cause is unlikely.
In those with underlying heart disease, effective control of congestive symptoms prevents pulmonary edema.
Dexamethasone is in widespread use for the prevention of high altitude pulmonary edema. Sildenafil is used as a preventive treatment for altitude-induced pulmonary edema and pulmonary hypertension, the mechanism of action is via phosphodiesterase inhibition which raises cGMP, resulting in pulmonary arterial vasodilation and inhibition of smooth muscle cell proliferation. While this effect has only recently been discovered, sildenafil is already becoming an accepted treatment for this condition, in particular in situations where the standard treatment of rapid descent has been delayed for some reason.
The initial management of pulmonary edema, irrespective of the type or cause, is supporting vital functions. Therefore, if the level of consciousness is decreased it may be required to proceed to tracheal intubation and mechanical ventilation to prevent airway compromise. Hypoxia (abnormally low oxygen levels) may require supplementary oxygen, but if this is insufficient then again mechanical ventilation may be required to prevent complications. Treatment of the underlying cause is the next priority; pulmonary edema secondary to infection, for instance, would require the administration of appropriate antibiotics.
Cardiogenic pulmonary edemaEdit
Acute cardiogenic pulmonary edema often responds rapidly to medical treatment. Positioning upright may relieve symptoms. Loop diuretics such as furosemide or bumetanide are administered, often together with morphine or diamorphine to reduce respiratory distress. Both diuretics and morphine may have vasodilator effects, but specific vasodilators may be used (particularly intravenous glyceryl trinitrate or ISDN) provided the blood pressure is adequate.
Continuous positive airway pressure and bilevel positive airway pressure (BIPAP/NIPPV) has been demonstrated to reduce the need of mechanical ventilation in people with severe cardiogenic pulmonary edema, and may reduce mortality.
It is possible for cardiogenic pulmonary edema to occur together with cardiogenic shock, in which the cardiac output is insufficient to sustain an adequate blood pressure. This can be treated with inotropic agents or by intra-aortic balloon pump, but this is regarded as temporary treatment while the underlying cause is addressed.
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- HeartFailureMatters.org Animation showing How Heart Failure causes Fluid Accumulation – Created by the European Heart Failure Association | 0 | 2 | 15 | 2 | 0 | 1 | 0 | 0.952429 | 3 | 3,557 |
When you have a child or children with autism, you probably spend more time with doctors and therapists than most other families. First, there’s the search for a diagnosis, then there are potential treatments, not to mention the other conditions—such as ADHD or gastrointestinal issues—sometimes associated with ASD.
All this means you’ve almost certainly come into contact with the ICD-10-CM. What does this string of letters and numbers mean, and how does it connect to autism? In this article, we’ll explore the ICD and how it impacts autism diagnosis.
What is the ICD-10-CM index?
The ICD-10-CM index is a version of the International Classification of Diseases, a tool created by the World Health Organization. It’s essentially a list of diseases, disorders, and other health conditions, all of which are categorized and labeled with a code made up of letters and numbers.
The ICD got its start as the International Statistical Institute’s International List of Causes of Death in 1893. Eventually, the World Health Organization took over its maintenance, and it was expanded to include all conditions, not just fatal ones. Every country that is a member of WHO must use the ICD to compile national death and disease statistics.
Member countries currently use the tenth edition of the ICD, called ICD-10. The International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) is a version created for use in the United States. The U.S. uses the ICD-10-CM to diagnose conditions and record patient information, and it uses the standard ICD-10 to classify data from death certificates.
ICD-10 came into effect globally in 1990, but the United States didn’t begin using it for mortality information until 1999 and didn’t fully transition to the ICD-10-CM until 2015. That’s why some websites will list what tenth revision codes are equivalent to those from its predecessor, the ICD-9—although there aren’t exact matches, since the transition to the tenth edition added about 55,000 new codes.
These codes have important purposes in the medical world. On a larger scale, public health officials use the data to conduct research and keep track of trends. For patients and caregivers, codes are usually used in hospital billing and insurance claims.
How is autism classified in the ICD-10-CM Index?
Autism is labeled with the code F84.0. It is a “billable code,” meaning it’s detailed enough to constitute a medical diagnosis. It falls under the section for mental and behavioral disorders (codes F00 through F99), the subsection of pervasive and specific developmental disorders (F80 through F89), and the smaller subsection of pervasive developmental disorders (F84).
The ICD defines a pervasive developmental disorder as “severe distortions in the development of many basic psychological functions that are not normal for any stage in development.” F84 itself is a non-billable code, so it can’t be entered into any system as a diagnosis, but every code that falls under it (F84.0 through F84.9) can.
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Looking at F84.0 autistic disorder
The description of F84.0 autistic disorder in the ICD is basically the same as other descriptions of autism—children with ASD will have difficulties with social interaction, language and communication skills, and repetitive behavior that become evident in early childhood, particularly before the age of three.
An ICD code may have “inclusion terms,” which are other conditions the code can be used for. Often, the inclusion terms are just synonyms of the primary one. In the case of code F84.0, the inclusion terms are autism spectrum disorder, infantile autism, infantile psychosis, and Kanner’s syndrome.
The ICD also has Type 1 Excludes Notes, which indicate when two codes should never be diagnosed alongside each other. In this case, autism and asperger’s syndrome are considered to be mutually exclusive (a position not taken by all diagnostic authorities, as we’ll see later). Asperger’s syndrome is called code F84.5 instead of code F84.0. The difference, according to the ICD, is that children with asperger’s don’t have the language and cognitive impairments that can be found in other autism spectrum disorders.
ICD coding allows professionals to include an additional code in their diagnosis, so they can further specify the disorder or identify any associated medical condition such as an intellectual disability. In that case, the patient would be coded for F84.0 autistic disorder as well as a code between F70-F79, which represent mild, moderate, severe, and unspecified intellectual disabilities.
Autism in the ICD-9
American children diagnosed with autism before 2015, when the ICD-9 phased out, may have received the code 299.0 or 299.1. Code 299.0 indicated “autistic disorder, current or active state” and 299.1 indicated “autistic disorder, residual state,” meaning the patient used to meet the criteria for an ASD diagnosis but no longer does. People with ASD in a residual state may still have symptoms found in autism, but not enough to maintain the diagnosis. Either way, both codes now fall under F84.0 autistic disorder.
Is the ICD-10-CM Index related to the DSM V?
The DSM V is the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, published by the American Psychiatric Association. It has been in effect since 2013. Unlike the ICD, it only covers mental conditions. But they have similar purposes in providing a shared, consistent set of terms and diagnostic criteria for health care professionals.
Because they’re created by two separate organizations, there are some discrepancies between the two manuals. For example, in the ICD-10, childhood disintegrative disorder, asperger’s syndrome, and pervasive developmental disorder-not otherwise specified each has its own code separate from autism. The American Psychiatric Association, however, collapsed each of these diagnoses under autism spectrum disorder.
That said, the indexes have very similar definitions of ASD. Both emphasize repetitive behavior, struggles with social interaction and communication, and the appearance of symptoms in early childhood.
The main difference between the two is that DSM-V codes can not be submitted for insurance claims. They are only useful for identification and diagnosis. If an insurance claim is submitted in the United States without an ICD code, it will be rejected.
Clearly, the ICD-10-CM is important for anyone with long-term medical diagnoses. As research is done and advances are made, the ICD will continue to change how we understand and classify conditions.
In fact, the ICD-11 is already on its way—WHO member countries will be allowed to implement it in 2022, though the United States isn’t expected to fully adopt it until the latter end of the decade.
Autism has a new code in the ICD-11: 6A02, now called “autism spectrum disorder” instead of “autistic disorder”. There is a new range of codes from 6A02.0 to 6A02.5, indicating whether the individual has impaired intellectual development or functional language. ICD-11 has also followed the DSM-V’s lead in including asperger’s syndrome under ASD.
We don’t know when ICD-11 will reach the U.S., or what, if any, modifications will be made to it. Either way, this article has hopefully helped you understand its purpose. Whether ASD is known as code F84.0, 6A02, 299.0, or something else in the future, autistic people and their loved ones represent a vibrant, supportive community.
Autism Speaks. (n.d.). DSM-5 and Autism: Frequently Asked Questions. Autism Speaks. https://www.autismspeaks.org/dsm-5-and-autism-frequently-asked-questions
Bielby, J. (2020, May 4). ICD-10, ICD-10-CM, & ICD-10-PCS. A.R. Dykes. https://guides.library.kumc.edu/icd10
Boyd, N. (n.d.). Diagnostic Codes: DSM-5 vs ICD-10. KASA. https://kasa-solutions.com/diagnostic-codes-dsm-5-vs-icd-10/
Holman, T. (2018, October). ICD-10-CM (Clinical Modification). TechTarget. https://searchhealthit.techtarget.com/definition/ICD-10-CM
World Health Organization. (2021). International Statistical Classification of Diseases and Related Health Problems (ICD). World Health Organization. https://www.who.int/standards/classifications/classification-of-diseases
World Health Organization. (2021). 2021 ICD-10-CM CODE F84.0. ICD List. https://icdlist.com/icd-10/F84.0
World Health Organization. (2021, May). 6A02 Autism spectrum disorder. ICD-11 for Mortality and Morbidity Statistics. https://icd.who.int/browse11/l-m/en#/http%3a%2f%2fid.who.int%2ficd%2fentity%2f437815624 | 0 | 4 | 2 | 0 | 0 | 0 | 21 | 0.612953 | 21 | 2,049 |
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Broadly speaking, injury is physical harm or damage to the body. It may be intentional or unintentional. If intentional, it may be self-inflicted (for example, suicide) or inflicted by another (for example, assault and homicide). The harm can be caused by any of the following things:
• an external force (such as a collision with an object)
• energy (heat, electricity, etc.)
• external or internal contact with a harmful substance (poisoning, etc.)
• the absence of an essential element (such as oxygen or heat) .
Normally, only harmful effects occurring over a short time are considered injury. (The term ‘injury' is used generally in reference to those conditions classified within the ICD group ‘external causes of morbidity and mortality' - V01 to Y98).
Assessing the total impact of injury is difficult. The vast majority of injuries do not result in hospitalisation or death and there are little systematic data on them other than those collected as part of large-scale population health surveys (such as the periodic National Health Surveys conducted by the Australian Bureau of Statistics). Thus, the vast majority of injuries are not recorded in routine data collections, and may not be brought to the attention of health policy-makers and program managers.
For injuries that are serious enough to be recorded in the routine data collections or are identified by specific studies, there are some issues with their classification. The classification of injury has generally followed the World Health Organization's International Classification of Diseases (ICD), which includes particular attention to the external cause and intention of the injury.
The 10th revision of the World Health Organization's International Classification of Diseases (ICD) is now applied in Australia to deaths and (in the somewhat more extensive ‘Australian Modification') to hospitalisation . The ICD-10 classification codes injuries in terms of their nature (for example, fracture of the vault of the skull) and the external cause of the injury (for example, assault by blunt instrument) . Because it is more useful for preventive purposes, most reporting of injury is in terms of external causes, the broad categories of which are as follows:
• accidents - transport accidents (including motor-vehicle accidents) and other external causes of accidental injury (falls, burns, accidental poisoning, etc.)
• intentional self-harm (including suicide)
• assault (including homicide)
• events of undetermined intent
• legal interventions and operations of war
• complications of medical and surgical care
• sequelae of external causes of morbidity and mortality
• supplementary factors related to causes of morbidity and mortality classified elsewhere.(this coding provides for factors like alcohol involvement, including blood alcohol levels if known).
The ICD categories are useful for broad epidemiological studies, but have serious limitations for detailed investigations for injury prevention. Many Indigenous injuries fall into categories in which there is little detail (for example, falls). In addition, it is apparent that culture affects the way in which information about an injury-causing event is described to investigators and clinicians, and the way this is interpreted through coding . An example is the uncertainty over how traditional Indigenous punishment practices should be coded - depending upon the perspective taken, they could be recorded as an accident, a legal intervention, or violence.
The magnitude of a problem can be assessed, but a detailed understanding of the causes cannot be obtained using the ICD system . Attempting to address these issues, Weeramanthri and Plumber proposed an alternative system to the ICD for the classification of cause of death. Their system emphasises the underlying rather than the direct cause of death, and the ICD classifications were replaced with the following categories: Land (diseases of the physical environment), Body (so-called ‘lifestyle diseases'), Spirit (diseases of poverty and cultural dislocation, including injury deaths), and Smoking-related. The authors calculated proportional mortality ratios and presented the results of a mortality analysis based on these ratios at feedback sessions and a workshop. No formal evaluation of this process was conducted, but informal feedback suggested that health information presented in this way was relevant and useful to the participating communities, and resonated more with the participants' world view.
The development of injury-prevention projects and programs depends on a solid understanding of the various factors contributing to specific injuries. Reflecting the great diversity of injuries - and the diversity of disciplines and backgrounds among involved in injury prevention - approaches investigating these factors range from the traditional epidemiological single-risk-factor approach to broad sociological methods.
The ecological model proposed in the World Report on Violence and Health provides one way of conceptualising the types of factors that need to be considered in the development of injury-prevention strategies . With a particular focus on violence, this model involves four levels:
There are, of course, other ways of conceptualising the factors contributing to injury. Regardless of which classification scheme is used, however, it is important that the scope is wide enough to ensure that the analysis of ‘causes' will reveal most of the factors that need to be taken into account in the development of preventive strategies.
This broad ecological approach to seeking causal factors is well established in the field of justice, being a feature of the work of the Royal Commission into Aboriginal Deaths and Custody , and also in the area of self-inflicted injury. It is a feature also of an analysis of road injuries in South Australia , but does not appear to be as widely used in the more traditional injury-prevention literature.
Overall, however, the understanding of contributory factors is weak for most areas of injury, including injury among Indigenous people . Information facilitating the analysis of risk factors and mechanisms of injury is relatively scarce and varies across the specific topic areas considered. Most studies that have sought to identify risk factors have failed to explore the interplay of risk factors (for example, young males' alcohol consumption, risk-taking, and exposure to hazardous environments) . If we are to understand how these factors influence each other, more longitudinal, in-depth research is required. Such research, with greater collaboration between fields of study, should also help us identify the point in the chain of events that can offer the greatest opportunity for intervention.
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* To whom correspondence should be addressed.
Received May 17, 2001; Revision received July 10, 2001
Cadherins are a family of membrane receptors that mediate calcium-dependent homophilic cell-cell adhesion. Cadherins play a key role in the regulation of organ and tissue development during embryogenesis. In adult organisms, these proteins are responsible for formation of stable cell-cell junctions and maintenance of normal tissue structure. Disruption in expression or function of cadherins may cause uncontrolled cell migration and proliferation during tumor development. This review focuses on the structure and physiological functions of classical cadherins.
KEY WORDS: cadherins, cell-cell adhesion, morphogenesis, signaling, oncogenesis
STRUCTURE OF CLASSICAL CADHERINS
The majority of members of the cadherin superfamily are transmembrane glycoproteins that pass the membrane only once. The N- and C-termini of the cadherin protein chain are located outside and inside the cell, respectively (Fig. 1). The extracellular portion of the cadherin molecule consists of a varying number of so-called cadherin domains that are highly homologous to each other. Each domain is comprised of approximately 110 amino acid residues . Classical cadherins contain five cadherin domains that are commonly designated as EC1-EC5 (beginning with the N-terminus of the molecule). The conformation of the cadherin molecule is stable only in the presence of Ca2+, whose binding with the extracellular portion of the polypeptide chain is prerequisite for cadherin-mediated cell-cell adhesion. Calcium-binding sites consisting of short highly conserved amino acid sequences are located between neighboring extracellular repeats . The cytoplasmic domain of classical cadherins is associated with the cytoplasmic proteins catenins, which, in turn, serve as intermediate linkers between the cadherins and actin filaments [10-12]. It is this cadherin-catenin complex that is required for providing normal cell-cell adhesion. In principle, extracellular cadherin domains per se are capable of homophilic recognition and binding. It was shown that cells that express mutant cadherins lacking the cytoplasmic domains can bind with substrate covered with purified cadherin ectodomains. However, in this case adhesion is much weaker than in the case of cells bearing full-size cadherins [11, 13, 14]. These data indicate that the formation of stable cell-cell junctions depends on the presence in the cadherin molecule of functionally active cytoplasmic domain and association of the latter with the cytoskeleton.
As mentioned above, cadherins mediate homophilic adhesion: during co-culturing of different types of cells, those cells first aggregate that bear identical cadherins on their surfaces . Similar dependence between cell sorting in the developing tissues and expression of different cadherins in them is observed during embryogenesis . The extracellular domains (primarily, the N-terminal domain EC1) play a key role in homophilic recognition between two cadherin molecules. It was shown that cells expressing chimerical E-cadherin, in which the EC1 domain was substituted with EC1 domain of P-cadherin, did not recognize the cells bearing native E-cadherin and aggregated with the P-cadherin-expressing cells . The site responsible for homophilic recognition contains 40 amino acid residues located in the C-terminal region of EC1. Blashchuk et al. assumed that sequence His-Ala-Val located in the C-terminal region of domain EC1 plays a key role in the interaction between cadherins because synthetic peptides containing this sequence effectively blocked mouse embryo blastomere assembling (a process that is mediated by cadherins). However, later it was shown that homophilic recognition also requires the presence of other regions located in the N-terminal domain. In addition, it was discovered that the sequence His-Ala-Val is contained only in the molecule of classical cadherins of type I that involves E- (epithelial), N- (neural), P- (placental), VE- (vascular endothelial), and R- (retinal) cadherins. The corresponding regions of type II classical cadherins that involve recently discovered cadherins designated by numbers 5-12 contain other amino acid residues [9, 10]. Type I and II cadherins also differ from each other in some amino acid residues.
Fig. 1. Structure of classical cadherins and their interaction with cytoplasmic proteins .
It should be noted that some cadherins can also mediate weak heterophilic interactions. In particular, E- and N-cadherin can bind with the integrin alphaEbeta7 and receptor for fibroblast growth factor [20, 21], respectively.
The role of the four other cadherin repeats (EC2-4) in the cell-cell interaction remains obscure. Possibly, only EC1 domain directly participate in homophilic binding, whereas the remaining domains act as spacers providing the required distance between the junction and cell surface. Nevertheless, they are required for cadherin-dependent adhesion: in the absence of other extracellular domains, the N-terminal domain alone cannot maintain functional binding or adhesive activity .
Numerous data that has accumulated to date show that the extracellular cadherin fragments exist in the form of stable parallel lateral dimers. Lateral dimers were revealed by X-ray analysis of N-cadherin EC1 domains and E-cadherin fragments including EC1 and EC2 domains . The existence of dimers was also shown for the whole extracellular fragment of C-cadherin . In the same experiments, it was also shown that the ability of C-cadherin monomers to aggregate significantly decreases compared to the dimers. To date, the mechanism of dimer formation is poorly understood. Apparently, N-cadherin dimers are stabilized by the hydrophobic interactions between the monomers , whereas in the case of EC1-EC2 fragment of E-cadherin dimeric structure is maintained by Ca2+ .
It is still unclear why dimers exert higher activity than monomers during cell-cell interaction. Two main views on this phenomenon exist. The first hypothesis proposes that dimers are bivalent, which increases their avidity. The second hypothesis implies that dimer formation is associated with the occurrence of a unique site ensuring homophilic binding, which is absent from the monomers. The mechanism of interaction of cadherin dimers located on the membranes of different cells has been also the subject of much controversy. Based on the results of X-ray analysis of NCD1, Shapiro et al. proposed the existence of a zipper-like self-assembling structure. This molecular zipper model (Fig. 2) logically explains the mechanism whereby numerous weak bonds can ensure highly efficient binding in the cell layer. However, some authors believe that cadherin zipper is an in vitro artifact and suggest an alternative hypothesis that was formulated based on the results of electron microscopic analysis of adhesive zone preparations obtained by the freeze-fracture method . Separate protein cylinders extending from one cell surface to another and binding with the similar structures on the neighboring cell are seen on the images. According to the second model, cadherin molecules (dimers or oligomers) act as discrete units and do not form zipper-like ordered structures on the cell surface .
Fig. 2. Two models of cadherin molecular organization in adhesive junctions. The molecular zipper model based on the results of X-ray analysis of N-cadherin EC1 domain is shown on the left. The model of cylindrical oligomers based on the results of electron microscopy of zonula adherens preparations obtained by the freeze-fracture method is shown on the right .
The conclusion that cadherin complexes interact with the cytoskeleton was first made based on the data that cadherins cannot be extracted with non-ionic detergents that effectively solubilized other membrane proteins [13, 25, 26]. It was shown later that the major cytoplasmic proteins associated with the cytoplasmic domain of cadherins and participating in cell adhesion are alpha- and beta-catenins, which mediate the interaction between the cadherins and actin cytoskeleton [11, 13, 25, 27-30]. The catenin-binding site was mapped on E-cadherin. It is located at the distance of 56 amino acid residues from the C-terminus of the molecule [25, 31]. Biochemical analysis with the use of purified catenins and recombinant cytoplasmic domain of cadherins [32, 33] and expression of beta-catenin deletion mutants [34-36] showed that beta-catenin directly binds to the cytoplasmic cadherin fragment and serves as a linker for alpha-catenin attachment.
The crucial role of the cytoplasmic domain of cadherin (and the catenin-binding site, in particular) is corroborated by numerous experiments. It was shown that deletion of the cytoplasmic domain or the catenin-binding site suppresses stable cadherin-mediated adhesion of cultured cells [11, 13]. Alternatively, overexpression of the catenin-binding site in the cultured cells , Xenopus laevis embryos , or in the intestinal cells of transgenic mice also entails disruption of cell-cell junctions. Such unusual, at first glance, result (at least, in the case of Xenopus laevis) can be, apparently, explained by competition of the expressed catenin-binding site with the endogenous cadherin for catenin binding.
The evidence for participation of alpha-catenin in cell adhesion was obtained on lung carcinoma cell culture that does not contain alpha-catenin and aggregates with each other very weakly despite the presence of cadherins on the cell surface. However, transfection with alpha-catenin cDNA restores cadherin-mediated adhesion in these cells [27, 29]. Rim et al. showed that alpha-catenin directly binds to actin filaments both in vitro and in vivo in the cultured cells. The actin-binding protein alpha-actinin contained in adhesive junctions apparently also interacts with alpha-catenin .
Participation of beta-catenin in cell adhesion was confirmed in experiments on Drosophila embryos using mutation analysis of protein armadillo, a homolog of beta-catenin . beta-Catenin is attached to the cytoplasmic domain of cadherin via its central region containing so-called armadillo repeats [34, 36]. These repeats (40 amino acid resides each) were first described in protein armadillo in Drosophila [40, 41]. alpha-Catenin binds to the N-terminus of beta-catenin [32, 34-36]. The role of a linker between cadherin and alpha-catenin is apparently the only function of beta-catenin in cell adhesion. It was shown that a chimerical molecule where the cytoplasmic domain of E-cadherin is substituted with alpha-catenin ensures cell adhesion in the absence of beta-catenin as successfully as the whole protein complex .
Plakoglobin (gamma-catenin) sometimes substitutes beta-catenin in the cadherin-catenin complex . However, its physiological role is not completely understood. Plakoglobin is the major component of the desmosomes , where it is associated with the desmosomal cadherins [44, 45]. The high extent of homology of plakoglobin to beta-catenin and armadillo [26, 46] implies that these proteins may have similar functions. However, mouse embryo cells lacking beta-catenin due to genetic recombination aggregate very weakly and readily dissociate despite the presence of plakoglobin in them . This is indicative of inability of plakoglobin to completely substitute for beta-catenin in cell adhesion. Deletion of the plakoglobin gene, which was also caused by homologous recombination, entails lethal changes in the heart structure and early death of the embryos, presumably due to disruptions in desmosomal junction formation . Other cytoplasmic proteins directly associated with cadherin are tyrosine phosphatases [49, 50] and the substrate for src-kinase p120cas [51-53].
Interestingly, the level of cadherin expression in the cell may affect catenin expression. Transfection of L-cells with E-, N-, or P-cadherin cDNA results in a significant increase in the catenin content without changing the catenin mRNA content. Hence, the presence of cadherins regulates catenin expression at the post-translation level .
It was also reported that cadherin cytoplasmic domain may mediate adhesion independently of catenins. Chimerical cadherin molecules in which cadherin cytoplasmic domain was substituted for the analogous domain of desmoglein-3 (one of desmosomal cadherins) that cannot bind catenins, mediates cadherin-dependent adhesion in the cultured cells . Thus, association with catenins is not the only way of participation of the intracellular cadherin domain in cell-cell adhesion.
CELL-CELL JUNCTIONS CONTAINING CADHERINS
Immunohistochemical analysis of tissues and cultured cells shows that cadherins most often are constituents of cell-cell adhesive junctions (Fig. 3). This type of junctions involves autotypic junctions between the layers of the same glial cell in the axon myelin sheath ; adhesive junctions in synapses, where cadherins link pre- and postsynaptic membranes in the regions adjacent to the neurotransmitter secretion areas [57, 58]; the intermediate disks between the cardiomyocytes ; and some other. The best-known type of cell-cell adhesive junctions is zonula adherens located at the apico-lateral border of the epithelial layer a little lower than the tight junctions. Actin bunches attached to the adhesive junctions girding the cell on the cytoplasmic side are located parallel to the membrane surface and form a united contracting network in the epithelial layer. Assembling of the belt-like zonula adherens is apparently the basis for the occurrence of the epithelial morphology of the cell layer [60-63]. During morphogenesis, folding of the epithelial layers into tubes is often attained by contraction of actin filaments contained in the zonula adherens, which is associated with narrowing the apical end of each cell in the apical layer and results in the cell layer bending [64, 65].
Besides cadherins and catenins, adhesive junctions contain numerous proteins (such as vinculin, ezrin, moesin, and radixin), protein components of the actin cytoskeleton, and integral membrane proteins (e.g., epidermal growth factor receptor, EGF) . Genetic studies on Drosophila revealed other components required for adhesive junction assembly. In particular, the genes whose mutations lead to disruptions in the course of zonula adherens assembling were identified in studies on Drosophila embryos. They involve the gene of beta-catenin homolog, armadillo, which is completely consistent with the view on the key role of this protein in cadherin-mediated adhesion [30, 67], as well as the genes crumb and stardust [67-69]. It was shown that gene crumb encodes the integral membrane protein that is required for epithelization of the ectodermic cells. In mutant individuals with inactive crumb gene normal cadherin-catenin complexes are expressed on the cell surface; however, their distribution is chaotic, leading to disruption in formation of mature zonula adherens in the epithelium [68-70].
Fig. 3. Cell-cell junctions formed by cadherins: a) epithelial zonula adherens; b) intermediate disks between the cardiomyocytes; c) adhesive junctions restricting the area of neurotransmitter secretion in the synapse; d) autotypic junctions between the glial cell layers in axon myelin sheath .
It should be noted that in many cells cadherins can mediate adhesion without formation of morphologically pronounced adhesive junctions. Even in the epithelium of some organs, where cell-cell adhesion depends on E-cadherin, zonula adherens is absent . Cadherin-mediated adhesion without cadherin accumulation in the adhesive junctions was also described for blastomeres , nerve ridge cells , and fibroblasts transfected with different types of cadherins .
REGULATION OF CADHERIN ACTIVITY
Cadherin-mediated adhesion can be regulated by a variety of extracellular signals, including growth factors [72-74], peptide hormones [75, 76], signals from gap junctions , and cholinergic receptor agonists . In response to these external stimuli, different signals are generated in the cell, of which protein phosphorylation is, apparently, the most important for the regulation of cadherin function .
Protein kinase C (PKC) participates in the activation of E-cadherin-dependent mouse embryo cell compacting, which was demonstrated with the use of a combination of pharmacological agonists and antagonists. Embryo compacting is accelerated by the addition of PKC-stimulating agents (e.g., phorbol ester and diacylglycerol) and inhibited by PKC-blocking agents , the PKC effect being blocked by the addition of anti-E-cadherin antibodies. However, it was not determined which PKC-mediated way is activated in this case.
Using a similar experimental approach, a potential inhibitory effect of tyrosine phosphorylation on cadherin function was shown. Several scientific groups discovered that enhancement of tyrosine phosphorylation (transfection with v-src or incubation of the cells with pervanadate) weakens cadherin-mediated cell-cell adhesion. Components of the cadherin-catenin complex (primarily beta-catenin) undergo tyrosine phosphorylation in response to v-src transfection and incubation with pervanadate [80-82]. Attenuation of adhesion in these experiments was blocked by herbimicin, which is also indicative of participation of tyrosine phosphorylation in the regulation of cadherin activity. It was also shown that v-src can affect cadherin-mediated adhesion irrespective of beta-catenin . The authors of this work used mutant E-cadherin that could directly bind with the C-terminal fragment of alpha-catenin and induce adhesion without the participation of beta-catenin. However, in this case transfection with v-src also significantly inhibited cell-cell adhesion.
Other data confirming the effect of tyrosine phosphorylation on cadherin-dependent adhesion are known. Tyrosine phosphorylation of beta-catenin is observed when cells are treated with hepatocyte growth factor (HGF) and EGF (agents that can induce dissociation of epithelial cells) . Tyrosine kinases or their substrates can associate with the cadherin-catenin complex. It is known that p120cas, a member of the armadillo protein family, is a substrate for both src kinases and receptor tyrosine kinases . It was shown that p120cas directly binds to the distal part of the cytoplasmic domain of E-cadherin, forming a whole complex with cadherin and beta-catenin or plakoglobin [52, 53, 84, 85]. Activation of the Erb-2/Neu receptor tyrosine kinase in the epithelial cells causes disassembling of the cell-cell junctions formed by E-cadherin, which results in the loss of the epithelial phenotype by the cells . EGF receptor tyrosine kinase also can bind to the cadherin-catenin complex . In addition, it was shown that cadherin-catenin complex can interact with receptor-dependent tyrosine phosphatases [49, 50, 88].
Cadherin function may also be affected by cell-cell communication via gap junctions. Inhibition of cell-cell communication by expression of the chimerical protein connexin 32/connexin 43 inhibitor (a protein that forms gap junctions) in Xenopus embryo cells leads to blastomere separation. A similar effect is observed when mutant cadherin is expressed in the embryo cells. This phenotype can be corrected by coexpression of connexin 37 that is insensitive to the inhibitor . Similarly, cell-cell junction assembling in Novikov hepatoma cells is suppressed by anti-connexin and anti-cadherin antibodies . The mechanism of signal transduction mediated by the gap junctions remains obscure. It is assumed that in this case cadherin-dependent adhesion and cell-cell junction assembling may be regulated via temporal increase in the concentration of Ca2+ and other small signal molecules (such as cyclic nucleotides or inositol phosphate) penetrating through the gap junctions and activating the intracellular processes that affect cadherin activity.
The strength of cell-cell interactions can be affected both by modulating cadherin activity and changing their expression level in the cell. It was demonstrated that an increase in cadherin content enhances cell adhesion [7, 90, 91]. It was also shown that cadherin expression in cultured cells is regulated by growth factors and peptide hormones [72, 73, 75, 76]. Another mechanism of regulation of cadherin activity is changing the extent of clustering of cadherin molecules in the junction area. As was mentioned above, lateral clustering of cadherin molecules can significantly affect the strength of cell-cell interaction. Changes in the extent of clustering can mediate rapid changes in cell adhesion strength. For example, mouse embryo blastomere compacting is associated with E-cadherin redistribution in the region of cell-cell junctions without any change in protein expression .
CADHERINS AND SIGNALING
To date, numerous data indicate that cell adhesion receptors can affect cell form, motility, and growth not only due to mechanical attachment of the cells to each other or to the substrate, but also by activating internal signaling . Some papers report that many effects of cadherin on cell behavior are rapid and apparently caused by a series of short-term signals rather than by assembling stable long-term cell-cell junctions [4, 6, 94]. However, until recently only indirect evidence of cadherin ability to induce the production of secondary messengers in the cell have been known. For instance, it was shown that axon outgrowth stimulated by N-cadherin is associated with changes in the cytoplasmic Ca2+ concentration and activation of G-proteins and tyrosine kinases. However, it was not clear whether these signals result from the direct interaction of N-cadherin molecules [95, 96]. Because different signal molecules (such as proteins belonging to the non-receptor src kinase family as well as some membrane receptors and phosphatases) were found in the cell-cell junctions of epithelial cells [49, 97, 98], it was suggested that these molecules can mediate cadherin-dependent signaling. Data on the direct effect of cadherins on the signal processes appeared only during the last two years. It was shown that inter-cadherin junctions in cultured fibroblasts induced oscillations in the cytoplasmic Ca2+ concentration, antibodies raised against the first domain EC1 mimicking this effect. The oscillations occurred in the regions of cell-cell interactions and coincided in time with translocation of actin and other cytoplasmic proteins into the adhesive complexes . N-Cadherin can regulate axon outgrowth by direct interaction with the EGF receptor, thereby activating the cascade of mitogen-activated protein kinases (MAPK) . The experiments on cultured keratinocytes showed that adhesive junction formation leads to a rapid activation of MAPK-dependent signaling and that this effect is mediated by E-cadherin. In addition, E-cadherin can stimulate MAPK by ligand-independent activation of EGF receptors . It also activates Cdc42, a low-molecular-weight GTPase belonging to the Rho family, which regulates the cytoskeleton structure .
For a long time beta-catenin, whose signal activity is well known, was considered as a candidate for the role of a messenger of signal transduction from cadherins, with which it is associated. beta-Catenin and its homolog armadillo from Drosophila are components of Wnt/wingless signal pathway that plays a key role in embryogenesis [102-104]. Recent data, however, indicate that the interaction between beta-catenin and cadherins is not prerequisite for manifestation of its signal activity. It was also shown that beta-catenin function as a cadherin partner during adhesive junction formation is not directly associated with its signal function in the cytoplasm and/or nucleus, where it affects transcription of genes by interacting with specific transcription factors [36, 105-111]. Free beta-catenin content in the cytoplasm is regulated by the protein product of the APC (adenomatous polyposis coli) gene. Formation of the complex between these two proteins is a signal for beta-catenin degradation. Conversely, triggering the Wnt signal pathway results in beta-catenin stabilization, its accumulation in the cytoplasm, and binding to the transcriptional factor Tcf, which, in turn, stimulates transcription of some genes. On the other hand, although the adhesive and signal functions of beta-catenin are separated, the formation of cell-cell junctions can apparently indirectly affect beta-catenin-dependent signaling. It was shown that overexpression of cadherins in the embryos of Xenopus laevis and Drosophila inhibited signal transduction via beta-catenin/armadillo [106, 112]. In Xenopus embryos, the inhibition is due to beta-catenin binding with C-cadherin on the inner surface of the cell membrane. As this takes places, beta-catenin is removed from its cytoplasmic pool, becoming inaccessible for participating in signaling. Thus, cadherins can regulate beta-catenin signaling activity by changing its distribution in the cell.
It cannot be ruled out, however, that cadherins indirectly contribute to signaling regulation. Approaching of the membranes of the neighboring cells during adhesive junction formation may enable the interaction of membrane receptors and their membrane-bound ligands on the neighboring cells and activate juxtacrine signaling. This hypothesis is corroborated by data on association of some signal molecules with the cadherin-catenin complexes and on high concentration of tyrosine kinase substrates in the regions of adhesive junctions. The group of juxtacrine receptors described to date involves notch, delta, sevenless, and bride-of-sevenless (boss) receptors participating in Drosophila embryogenesis [113, 114] and associated with the membrane form of tumor necrosis factor (TNF) and transforming growth factor (TGFalpha) . It is tenable to assume that signaling via such receptors depends on the proximity of the surface of adjacent cells and, respectively, on formation of inter-cadherin junctions. This hypothesis is confirmed by the fact that expression of cadherins in the fibroblasts entails communication enhancement via gap junctions .
THE ROLE OF CADHERINS IN MORPHOGENESIS
The formation of tissues and organs during embryogenesis is determined by a number of processes coordinated in time and space, such as cell aggregation, polarization, differentiation, and migration. Because cell-cell and cell-nuclear matrix adhesive junctions play a key role in all these events, adhesion receptors are often called morphoregulatory molecules. One such adhesion-dependent processes is selective cell segregation. This phenomenon was discovered as early as in the 1950s. In classical works in embryology, it was shown that suspended cells from different amphibian blastophylla are capable of homotypic reaggregation to form junctions only with similar cells in correspondence with their histogenetic origin . Later it was discovered that this homotypic aggregation is based on selective expression of specific adhesion molecules on different subpopulations of cells. The role of cadherins in this process was revealed by Nose et al. . The L-cells were transfected with cDNA of either E- or P-cadherin. The suspensions were then mixed in vitro and analyzed for cluster formation. Under these conditions, highly selective adhesion between cells expressing cadherins of the same type was observed.
Another morphogenetic process in which cadherins play a key role is cell condensing (i.e., transition of cell population from dispersed state to condensed solid formation). An example of such condensing is blastomere assembling at the early stages of embryogenesis. E-Cadherin plays a crucial role in cell condensing in mouse embryo morula: the embryo structure is disrupted as a result of treatment of the cells with blocking anti-E-cadherin antibodies, introduction of antisense nucleotides to E-cadherin mRNA into the cell, and in transgenic mice defective by the gene encoding this protein [118-123]. Injection of antisense nucleotides into Xenopus laevis oocytes, which decreases expression of EP-cadherin (a Xenopus laevis protein homologous to E- and P-cadherins), significantly attenuates adhesion between the blastomeres and entails disruption of the embryo structure .
Numerous studies performed both in intact embryos and cultured cells revealed significant correlation between epithelization of mesenchymal cells and expression of specific cadherins in them. During somite development, mesenchymal cells comprising its future wall are polarized and temporarily form epithelium-like structures, the expression of N-cadherin in them significantly increasing [64, 65, 125]. Transfection of cultured mesenchymal cells with cDNA of different cadherins results in their epithelization [13, 126-128], whereas inhibition of cell-cell interactions by anti-cadherin antibodies leads to the loss of epithelial phenotype by the cells and stimulates cell motility and invasiveness [129-131].
One of the most vivid examples of participation of cadherins in morphogenesis is their role in the central nervous system development. At different stages of embryogenesis and in different structural layers, neuroepithelial tissues express more than 20 different cadherins involved in all key events of neurogenesis, beginning from selective aggregation of the cells at the earliest stages of embryo development and finishing with the formation of synapses [132-137]. Cadherins play a key role during neuroectoderm sorting and neural tube formation. It was also shown that before segregation of the neuroectoderm from the ectoblast in neurula, a coordinated decrease in the expression of E-cadherin and increase in that of N-cadherin occurs in the cells of future neuroectoderm. It is believed that it is N-cadherin that is responsible for selective cell uniting in the neural plate [64, 65, 138]. Interestingly, normal neural tube is formed in transgenic mice defective in the N-cadherin gene. Apparently, in this case N-cadherin is functionally substituted with other adhesion molecules (presumably, cadherin-6) . It is known that the coordinated change in the cell shape induced by microfilament contraction in zonula adherens underlies neural tube folding and other morphogenetic processes that require change in the shape of the epithelial layers [64, 65]. Further development of the neural tube involves its segregation to separate regions due to local expression of different cadherins. For example, selective distribution of E- and R-cadherins, cadherin-6, and cadherin-8 in different regions of embryonic brain is observed [135, 136, 140, 141]. The possibility of selective segregation of nerve cells that express cadherins of the same type was demonstrated in vitro. In vivo such segregation of the neural tube to segments apparently prevents the migration of nerve cells between adjacent regions of the developing brain .
Normal expression of cadherins is required for neurite outgrowth activating and regulating. The expression of dominant-negative functionally inactive N-cadherin in developing frog retina blocks the axon and dendrite outgrowth. Those axons that are still formed are usually shorter and often do not have growth cones . In the experiments in vitro, it was shown that growth and migration of axons change during neuron culturing on the substrates containing recombinant cadherins. In particular, recombinant N-cadherin enhances adhesion of axons to the substrate and enables their projecting in the direction of higher concentrations of the recombinant protein. Similar growth stimulation is observed when the neurons are cultured on the monolayer of cells transfected with N-cadherin cDNA [8, 95, 143-146]. Such effect on axon projecting is apparently due to the interaction of N-cadherin with FGF receptor with subsequent MAPK activation . By contrast, another member of the cadherin family, T-cadherin, inhibits axon outgrowth [137, 147]. Thus, the coordinated action of different cadherins and other adhesion receptors expressed on the axon membrane and surrounding tissues ensure navigation of axon projecting to the peripheral targets.
Cadherins also play a key role in setting and stabilization of junctions between the neurons and formation of neural nets and neuromuscular junctions [148-153]. In mouse postnatal brain, cadherins of the same type are expressed in functionally related regions (e.g., in the thalamus nucleus and related cortex regions ). During chick eye development N-cadherin stabilizes the junctions between the axon termini and their targets. Formation of a branched net of neural termini in the retina may be blocked by injecting anti-N-cadherin antibodies . It was shown that in synapses cadherins anchor the pre- and postsynaptic membranes, bordering the area of neurotransmitter secretion [57, 58]. E-Cadherin is also present in the myelin sheath of nerves, where it forms autotypic adhesion junctions between the plasma membrane layers of the same Schwann cell (Fig. 3).
CADHERINS AND ONCOGENESIS
The ability of tumor cells for uncontrolled growth, migration, invasion into surrounding tissues, and metastasizing is often associated with disruption of cell-cell and cell-extracellular matrix junctions [156, 157]. For this reason, special attention is currently paid to identification and characterization of cell adhesion receptors involved in tumor development. With regard for the role of cadherins in cell-cell adhesion, maintenance of tissue structure, and regulation of epithelial cell phenotype, it was assumed that the disruption of cadherin-dependent cell-cell interactions in the epithelium may cause attenuation of cell-cell junctions, loss of epithelial phenotype, enhancement of cell motility, removal of contact suppression of growth, and, as a result, uncontrolled proliferation and invasion of tumor cells . The majority of studies in this area focus on the role of E-cadherin in malignant cell transformation. In many works, it has been shown that E-cadherin expression is decreased or absent from different carcinomas (esophagus, stomach, or breast) [159-162]. Abnormal distribution of E-cadherin in tumor cells was often observed (it was absent from the regions of adhesion junctions). It should be noted that E-cadherin expression was most often decreased in the undifferentiated aggressive carcinomas that have high invasive potential .
Similar results were obtained on cultured cells. Frixen et al. also reported that carcinoma cell lines with the epithelial noninvasive phenotype expressed E-cadherin, whereas the latter was absent from the cells with the fibroblastoid phenotype. Navarro et al. revealed reciprocal dependence between the amount of E-cadherin expressed on the cell surface of different carcinomas and the ability of these cells for invasion. Malignant transformation of MDCK epithelial cells (which are noninvasive in normal state) as a result of injection of Harvey and Maloney sarcoma virus to the cell culture is accompanied by a decrease in E-cadherin expression on the cell surface. A similar change of MDCK cell phenotype from noninvasive for invasive is also observed after disruption of cell-cell junctions in the presence of anti-E-cadherin antibodies . Conversely, transfection of the carcinoma cells with E-cadherin cDNA restores normal cell phenotype, decreases invasiveness and migration, and suppresses tumor growth [163-165].
The few studies on the role of P-cadherin in oncogenesis also revealed a correlation between decreased expression of this protein and the invasiveness of lung carcinomas and melanomas . Unexpected results were obtained when studying the effect of N-cadherin on tumor cells. It was discovered that expression of this protein is significantly enhanced in invasive undifferentiated breast carcinoma cells . It was also shown that an increase in N-cadherin expression in the carcinoma cells simultaneously with the decrease in E- and P-cadherin expression changes the phenotype from epithelial to mesenchymal . Transfection of MCF-7 carcinoma cells with N-cadherin cDNA significantly enhances the invasiveness and stimulates metastasis development despite the presence of E-cadherin in these cells . Such an opposite effect of cell-cell adhesion mediated by E- and N-cadherins on cell behavior may be due to the ability of E-cadherin to form stable cell-cell junctions that prevent cell migration, whereas N-cadherin can form labile junctions required for such dynamic processes as axon projecting or migration and invasion of tumor cells .
Other components of cadherin complexes (primarily catenins) can also affect the growth and migration of transformed cells. As was mentioned above (see Cadherins and Signaling), normal expression of free beta-catenin in the cytoplasm is maintained by the oncosuppressing protein APC that binds with excessive beta-catenin and activates its degradation . In patients with hereditary polyposis, who are predisposed to intestine cancer, mutations in the APC gene or directly in beta-catenin gene are often observed. As a result of these mutations, the APC protein lacks its ability to regulate beta-catenin level in the cytoplasm, which leads to uncontrolled activation of the Tcf transcription factor by beta-catenin and development of intestine tumors .
T-CADHERIN IS AN ATYPICAL MEMBER OF THE CADHERIN FAMILY
T-Cadherin (truncated) (or H-cadherin (heart), or cadherin-13) is one of the most unusual members of the cadherin superfamily. Although its N-terminal domain EC1 does not contain the His-Ala-Val sequence, its extracellular part comprised of five cadherin repeats is very similar in structure to the classical cadherins. A unique feature of this protein is the absence of both the transmembrane and cytoplasmic domains. It is anchored in the membrane via glycosylphosphatidylinositol (GPI) that attaches to the mature protein after cleavage its C-terminal sequence during processing in the endoplasmic reticulum . Despite the absence of the cytoplasmic domain, T-cadherin can mediate any weak homophilic adhesion of the suspended cells . The mechanisms of formation of cell-cell junctions via T-cadherin and classical cadherins are apparently significantly different because the majority of cadherins ensure adhesion only when they contain the cytoplasmic domain that mediates their binding with the cytoskeleton [11, 13]. Another unusual property of T-cadherin is simultaneous expression on the cell surface of its two forms (the mature protein and partially processed precursor containing an uncleaved propeptide, whose function remains obscure) .
T-Cadherin was first discovered in chick nervous system [137, 175]. Later its human homolog called cadherin-13 was identified . The only physiological function of T-cadherin established so far is its participation in the regulation of neuron growth during embryogenesis. During formation of chick embryo hind limbs, the outgrowing axons avoid those regions where T-cadherin is expressed . Neuron culturing on substrate containing recombinant T-cadherin significantly inhibits axon growth . Contact suppression of axon growth as a result of homophilic binding between T-cadherin molecules located on the axon membrane and surrounding mesenchymal tissues is apparently a navigating mechanism whereby the direction of nerve fiber growth is determined.
Numerous recent data indicate that malignant tumor development is associated with the changes in T-cadherin expression. The loss of chromosome 16q24 locus containing T-cadherin gene correlates with the development of pancreas, lung, stomach, and ovary cancers [177-182]. The transfection of tumor cells with T-cadherin cDNA entails a decrease in the proliferative and invasive activities both in vitro and in vivo as a result of challenging the mice with tumorigenic cell lines as well as the loss of cancer cell sensitivity to the action of growth factors .
The mechanisms of T-cadherin effect on cell adhesion and proliferative activity are still unknown. It cannot be ruled out that the maintenance of mechanical junctions between the cells is not the main function of this protein. It is most likely that it serves as a signal receptor, a sensor that allows the cell to sense its environment. This hypothesis is corroborated by the data on T-cadherin distribution in the membrane: in the polarized intestinal cells it is located on the apical part of the cell rather than in the adhesive junctions on the basolateral cell surface . It has long being known that many other GPI proteins may activate intracellular signaling [186-188]. The absence of the cytoplasmic domain in these proteins implies the presence of a membrane adapter protein. Owing to the interaction with the latter, the signal can be relayed across the membrane from the GPI proteins into the cell. We showed that, similar to other GPI proteins, T-cadherin is located on the cell surface in special plasma membrane domains (caveolae and lipid rafts) , which also contain other signal molecules (such as G-proteins, src kinases, rasproteins, and transmembrane receptors of growth factors ). It cannot be excluded that some of these molecules may serve as messengers during activation of T-cadherin-dependent signaling.
In our laboratory, the main attention is focused on investigation of the role that T-cadherin plays in the cardiovascular system function. Cell adhesion molecules play a crucial role in the maintenance of normal structure of vascular walls. The development of different pathologies (such as atherosclerosis and restenosis after balloon angioplasty and atherectomy) is characterized by enhanced migration, proliferation, and phenotypic modulation of the endothelial cells, which is often associated with disruption of cell-cell and cell-extracellular matrix junctions [191, 192]. The expression and functions of T-cadherin in the cardiovascular system have not been studied before. We performed a comparative study of T-cadherin expression in different human organs and tissues. The results show that T-cadherin content is maximal in the aorta, carotid, iliac, and kidney arteries, and in heart. In aorta wall, T-cadherin is contained in the endothelial and smooth muscle cells and pericytes. Its expression in the smooth muscle cells depends on the cell phenotype and proliferative activity [193-195] and increases in sclerotic lesion of vascular walls . Preliminary studies performed on the model of balloon catheterization of rat carotid artery indicate that T-cadherin expression in smooth muscle cells increases in restenosis. The content of this protein is also elevated in the endothelium isolated from tumor vasculature . In addition, anti-T-cadherin antibodies can affect the phenotype, adhesion, and motility of the endothelial cells in vitro (our unpublished data). With regard for these data, it is likely that T-cadherin plays a key role in the regulation of cell phenotype, migration, and growth, as well as in maintenance of vascular wall structure.
Study of the interaction of heterophilic interactions between T-cadherin and blood plasma lipoproteins is also of great interest. Originally, the work of our group was aimed toward searching for the receptors that mediate the hormone-like effect of low-density lipoproteins on the systems of intracellular signaling in smooth muscle cells in human vasculature [197, 198]. On the surface of membranes of aorta smooth muscle cells, we discovered two unusual lipoprotein-binding proteins with molecular weight of 105 and 130 kD. The characteristics of these proteins are indicative of their participation in lipoprotein-dependent signaling [199, 200]. After isolation of these receptors from human aorta medium and determination of their amino acid sequence, we discovered that the 105-kD protein is mature T-cadherin , whereas the 130-kD protein is its partially processed precursor . It is known that increased lipoprotein content in blood plasma is a risk factor of development of vascular pathologies based on increased proliferation and migration of smooth muscle cells. A distinct relationship between atherosclerosis and restenosis pathogenesis and low-density lipoprotein content in blood was demonstrated . It cannot be ruled out that lipoprotein binding to T-cadherin may affect T-cadherin-dependent regulation of growth and motility of vascular cells, thereby contributing to development of cardiovascular diseases.
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Attention Deficit Hyperactivity Disorder (ADHD), including the different types and who gets them.
- Bipolar Disorder Facts about bipolar disorder, including different types and symptoms.
- ADHD Attention Deficit Hyperactivity Disorder (ADHD), including the different types and who gets them.
- Adult ADHD Facts about attention deficit hyperactivity disorder (ADHD) in adults.
- Alzheimer's Disease Facts about Alzheimer’s Disease, including the symptoms and stages.
- Autism Spectrum Disorder Get the facts about Autism Spectrum Disorder (ASD).
- Chronic Pain Facts about chronic pain, including body parts most commonly affected.
- Clinical Depression Clinical depression facts; symptoms & other depressive disorders.
- Depression Facts about depression, including the symptoms of the condition.
- Diabetic Neuropathy Facts about diabetic neuropathy, including the symptoms and doctors.
- Epilepsy Facts about epilepsy, including different types, symptoms and causes.
- View All Care Guides Prepare for your next visit with our extensive library of Care Guides
Dr. James R Wright III has the following 2 specialties
A psychiatrist is a doctor with specific training in the diagnosis and treatment of mental illness.
He or she can not only provide the counseling necessary to both diagnose and treat a patient, but can also prescribe medication when needed. In some cases, a psychiatrist will only provide the medication and the counseling will be provided by another healthcare specialist, like a certified counselor or psychologist.
Like other doctors, psychiatrists employ diagnostic tools like CT scans and MRI in order to observe the structure and function of a patient's brain.
Once a diagnosis is made, these specialists may use behavior or cognitive therapy in order to address the patient's condition, or a multitude of other types of therapy, in conjunction with or in place of medication.
A neurologist is a physician who diagnoses and treats disorders of the nervous system which is comprised of the brain, spinal cord and nerves. These doctors do not perform surgery, but refer patients to neurological surgeons when they determine that surgical intervention is necessary.
Some of the conditions that neurologists diagnose and treat are epilepsy, aneurysms, hydrocephalus, Parkinson's disease, multiple sclerosis, stroke, spinal disc herniation, and spinal disease.
In addition to using diagnostic tests like MRI, CT scans, EEG and EMG, neurologists also employ neurological testing to gauge muscle strength and movement, balance, reflexes, sensation, memory, speech, and other cognitive abilities.
Dr. James R Wright III has the following 15 expertise
- Mood Disorders
- Sleep Disorders
- Erectile Dysfunction (ED)
- Obsessive-Compulsive Disorder (OCD)
- Anxiety Disorders
- Closed Head Injuries
- Personality Disorder
- Attention Deficit Disorder (ADD) / Attention Deficit Hyperactivity Disorder (ADHD)
- Mental Illness
- Depressive Disorder
- Attention-Deficit/Hyperactivity Disorder (ADHD)
- Bipolar Disorder
Dr. James R Wright III is Board Certified in 1 specialty
See the board certifications this doctor has received. Board certifications provide confidence that this doctor meets the nationally recognized standards for education, knowledge and experience.
Showing 5 of 97
He fell asleep while I was talking to him. I feel like he never listened to me because his eyes wouldn't meet mine. He was looking my way but I had to repeat things several times. The staff-disorganized, forgot to answer faxes from my pharmacy which led me to going to the ER. They NEVER answer the phone. They have been rude to my husband and I by informing us that if we didn't pay a 25.00 balance that my appt would be canceled, I would be fired as a patient & my account would go to their collection agency. Wow! My husband called on the weekend and his answering service tried contacting Dr. Wright and he never returned any of my calls. I was suicidal and in a dark place. Beware. I felt like a number in the last couple of years.
Ive been a patient for 2 years. I was seeing Jeanete who represented herself as a nurse practitioner. After many visits & always feeling like she would throw medication at me, I did some research. She's not even a nurse practitioner as her cards, door & staff says she is. THIS IS AGAINST THE LAW to misrepresent herself! I saw other patient charts laying around. Front desk staff named Tanya, should be fired. She was rude to me several times I called. She refused my refill & I had an appt within the week. I had major withdrawals and almost took a handful of pills because I didn't want to live once I started feeling the withdrawal of NOT having my medication. jeanete gave me her cell # but would never respond to my texts.She spent our appts cussing and complaining about the office staff. All of their old staff is gone and they were the ones who were caring. The new staff is awful. I started with the doctor & he was the most unresponsive man I've ever met. DO NOT GO!
Patients' Choice Award (2009, 2010, 2018)
Patients' Choice recognition reflects the difference a particular physician has made in the lives of his/her patients. The honor is bestowed to physicians who have received near perfect scores, as voted by patients.
On-Time Doctor Award (2014)
Vitals On-Time + Promptness Award recognizes doctors with consistent high ratings for timeliness of appointments. The honor is granted based on a physician's overall and promptness scores.
Compassionate Doctor Recognition (2011)
Compassionate Doctor certification is granted to physicians who treat their patients with the utmost kindness. The honor is granted based on a physician's overall and bedside manner scores.
43 Years Experience
The University Of Texas School Of Medicine At San Antonio
Graduated in 1975
University Of Texas Health Science Center
Dr. James R Wright III accepts the following insurance providers.
BCBS Blue Card
- BCBS Blue Card PPO
- BCBS TX Blue Advantage HMO
- BCBS TX BlueChoice
- BCBS TX HMO Blue Texas
- CIGNA HMO
- CIGNA LocalPlus
- CIGNA Open Access Plus
- CIGNA PPO
- First Health PPO
- Multiplan PPO
- PHCS PPO
Locations & DirectionsJames Robert Wright Iii Md, 14340 Torrey Chase Blvd Ste 325, Houston, TX
Dr. James R Wright III is similar to the following 3 Doctors near Houston, TX. | 0 | 2 | 6 | 1 | 0 | 0 | 0 | 0.966536 | 1 | 1,359 |
Get the facts about attention deficit hyperactivity disorder (ADHD) in adults, including the different types and symptoms of each.
- Bipolar Disorder Facts about bipolar disorder, including different types and symptoms.
- ADHD Attention Deficit Hyperactivity Disorder (ADHD), including the different types and who gets them.
- Adult ADHD Facts about attention deficit hyperactivity disorder (ADHD) in adults.
- Alzheimer's Disease Facts about Alzheimer’s Disease, including the symptoms and stages.
- Autism Spectrum Disorder Get the facts about Autism Spectrum Disorder (ASD).
- Chronic Pain Facts about chronic pain, including body parts most commonly affected.
- Clinical Depression Clinical depression facts; symptoms & other depressive disorders.
- Depression Facts about depression, including the symptoms of the condition.
- Diabetic Neuropathy Facts about diabetic neuropathy, including the symptoms and doctors.
- Epilepsy Facts about epilepsy, including different types, symptoms and causes.
- View All Care Guides Prepare for your next visit with our extensive library of Care Guides
Dr. Luke P Peris has the following 2 specialties
A psychiatrist is a doctor with specific training in the diagnosis and treatment of mental illness.
He or she can not only provide the counseling necessary to both diagnose and treat a patient, but can also prescribe medication when needed. In some cases, a psychiatrist will only provide the medication and the counseling will be provided by another healthcare specialist, like a certified counselor or psychologist.
Like other doctors, psychiatrists employ diagnostic tools like CT scans and MRI in order to observe the structure and function of a patient's brain.
Once a diagnosis is made, these specialists may use behavior or cognitive therapy in order to address the patient's condition, or a multitude of other types of therapy, in conjunction with or in place of medication.
A neurologist is a physician who diagnoses and treats disorders of the nervous system which is comprised of the brain, spinal cord and nerves. These doctors do not perform surgery, but refer patients to neurological surgeons when they determine that surgical intervention is necessary.
Some of the conditions that neurologists diagnose and treat are epilepsy, aneurysms, hydrocephalus, Parkinson's disease, multiple sclerosis, stroke, spinal disc herniation, and spinal disease.
In addition to using diagnostic tests like MRI, CT scans, EEG and EMG, neurologists also employ neurological testing to gauge muscle strength and movement, balance, reflexes, sensation, memory, speech, and other cognitive abilities.
Dr. Luke P Peris has the following 12 expertise
- Personality Disorder
- Sleep Disorders
- Attention Deficit Disorder (ADD) / Attention Deficit Hyperactivity Disorder (ADHD)
- Bipolar Disorder
- Attention-Deficit/Hyperactivity Disorder (ADHD)
- Depressive Disorder
- Manic Depressive Disorder
- Mental Illness
- Mood Disorders
Dr. Luke P Peris has 0 board certified specialties
Showing 5 of 25
I was referred to Dr Peris when I moved to Dallas. I had been medicated off and on for 15 years before him and never felt well. I saw Dr Peris for 9 years until I moved. He was the best Psychiatrist I have been to. He had me take a med combo that worked promptly. He is on time, easy to schedule a last minute appointment,and he also returns phone calls within hours. Even on weekends.
In all honesty, I picked Dr. Peris because his office is across the street from my job. But I lucked out. Getting an appointment is easy, especially compared to some places I have gone. His office manager, Eleanor, is awesome. She takes care of everything, is well organized and always calls to remind me of appointments. I am never left waiting for long periods of time. And Dr. Peris himself is pretty great. I've had doctors where they literally saw me for 5 minutes before handing me a refill and pushing me out the door, still holding my list of concerns that I had wanted to discuss. Dr. Peris doesn't do that. If you have a laundry list of things to discuss, then he has the time to discuss them with you. He is knowledgeable about a large spectrum of topics. He is kind and considerate. Even if I change jobs, I won't change doctors.
We have been appreciative patients of Dr Peris for 3 years. I have found him to be respectful, helpful, and caring. His approach is supportive and conservative. One of his strengths is that he really does know his meds and the many ways they can be used well. Words cannot express our thankfulness for Dr Peris.
I've been to great psychiatrists, and I've been to terrible ones. Dr. Peris is the very best. He's also a therapist, so he isn't solely focused on doling out medication. He understands the value of combining therapy, diet, exercise, etc. with drug therapy. His office administrator, Eleanor, is also wonderful. A friend referred him to me, and I've since referred him to several other people. In the six years I've been seeing him I've never left his office dissatisfied.
On-Time Doctor Award (2016, 2017, 2018)
Vitals On-Time + Promptness Award recognizes doctors with consistent high ratings for timeliness of appointments. The honor is granted based on a physician's overall and promptness scores.
Compassionate Doctor Recognition (2015, 2016, 2017, 2018)
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34 Years Experience
University Of Oklahoma College Of Medicine
Graduated in 1984
Nassau University Medical Center
Dr. Luke P Peris accepts the following insurance providers.
- Aetna Managed Choice POS Open Access
BCBS Blue Card
- BCBS Blue Card PPO
- BCBS TX Blue Advantage HMO
- BCBS TX BlueChoice
- BCBS TX HMO Blue Texas
- CIGNA HMO
- CIGNA LocalPlus
- CIGNA Open Access Plus
- CIGNA PPO
- Multiplan PPO
Locations & DirectionsLuke Prakash Peris Md, 14800 Quorum Dr Ste 465, Dallas, TX
Dr. Luke P Peris is similar to the following 3 Doctors near Dallas, TX. | 0 | 2 | 9 | 1 | 0 | 0 | 0 | 0.956358 | 1 | 1,382 |
- 1 Disease Entity
- 2 Diagnosis
- 3 Management
- 4 References
Round hole of retina without detachment ICD-10 H33.32 (non-billable); retinal breaks without detachment ICD-10 H33.3 (billable)
An atrophic retinal hole is a break in the retina not associated with vitreoretinal traction.
Etiology and Risk Factors
Idiopathic atrophic retinal hole is the most common presentation. There are no generally accepted risk factors for this condition but lesions have been cited more often in younger myopic patients. It has been estimated about 5% of the general population has atrophic holes. Atrophic holes often present in the peripheral (temporal or superior) retina. There appears to be no sex predilection.
Atrophic retinal holes are full thickness retina breaks often existing in the peripheral retina. They are the result of atrophic changes/thinning within the sensory retina that is not induced by vitreous adhesions. Often, these lesions are found in association with lattice degeneration. The incidence of this association has been reported as high as 43%.
Retinal holes are the result of chronic atrophy of the sensory retina. These lesions often take a round or oval shape. It has been postulated that the pathogenesis of this lesion stems from an atrophic pigmented chorioretinopathy that is associated with retinal vessel sclerosis and a disturbance of the overlying vitreous. As the blood supply to the retina is shut down, the retinal tissue subsequently dies in conjunction with degeneration of the surrounding vitreous. This pathology precludes traction of the vitreous to the underlying sensory retina.
There are no preventative measures to the development of atrophic retinal holes.
This is a clinical diagnosis based on history and clinical exam, including slit lamp and dilated fundus examination.
Patients with atrophic retinal holes generally present for routine ocular examinations. This type of lesion is generally an incidental finding. Some patients may present with a complaint of photopsias (flashing lights) or other visual disturbance if associated with a symptomatic posterior vitreous detachment.
Slit lamp examination with special attention to the peripheral fundus is important in the evaluation of this disorder. An indirect ophthalmologic examination with scleral depression may be required to indentify retinal holes adjacent to the ora serrata.
Careful attention should be used when examining myopic patients and those patients with lattice degeneration due to the increased incidence in these populations.
Retinal holes are full thickness breaks in the sensory retina. They may be surrounded by pigmentation, especially if chronic and embedded withing a patch of lattice degeneration. As mentioned prior, they take a round or oval shape and lack a "tag" that is seen with a classic horseshoe tear. Subretinal fluid may accompany these lesions. Subretinal fluid, if present, may involve up to 360 degrees of the lesion's edge and spread slowly under the surrounding retina resulting in either a symptomatic or asymptomatic retinal detachment.
Atrophic holes are asymptomatic in a majority of patients. If associated with a retinal detachment patients may experience visual symptoms such as photopsias, floaters, or loss of visual field.
The diagnosis of an atrophic retinal hole is a clinical one. There are no studies currently used to diagnose or classify this type of retinal pathology. To differentiate this lesion from an operculated retinal hole, a clinician needs to look for an isolated detachment of the sensory retina adherent to the overlying vitreous without traction to the edges of the retinal hole. The absence of vitreoretinal traction, round/oval shape, and a free retinal flap will also assist in differentiating this lesion from a horseshoe retinal tear.
Atrophic retinal holes are diagnosed during routine clinical examination. Depending on how far into the peripheral retina the lesions are located a clinician has the option of using either direct or indirect ophthalmoscopy. Scleral depression is sometimes needed to fully assess the pathology.
Direct ophthalmolscopy utilizes a slit lamp for the examination and the choice of either a non contact 78 or 90 diopter lens (various other similar lenses are available) versus a Goldmann triple mirror contact lens. The 78 and 90 diopter lens provides an image of the retina which is best for viewing the posterior pole and mid periphery of the fundus. A skilled physician can often times manipulate the slit lamp and provide patient direction which allows for a good view of the peripheral fundus. The Goldmann triple mirror lens is designed specifically to allow for a broader view of the fundus to include the posterior pole and extend out to the ora serrata and ciliary body. Other wide angle contact lenses can be used as well.
Widefield funduscopic photography (e.g., Optos) can be beneficial in documenting atrophic retinal holes.
No laboratory tests are indicated in cases of atrophic retinal holes.
The clinical appearance of atrophic retinal holes is very characteristic. Despite this there are several possible diagnoses that should be considered which include horseshoe retinal tear, lattice degeneration, operculated retinal hole, snailtrack degeneration, and retinoschisis. Sometimes round area of normal retina when surrounded by white without pressure may appear like a retinal hole on clinical examination.
There is no mandatory therapy for this condition in general. According to the Preferred Practice Patterns set forth by the American Academy of Ophthalmology, treatment is rarely recommended for atrophic retinal holes. Some studies suggest that prophylactic laserpexy may be considered for eyes with retinal holes when there are active symptoms, when there is accompanying subretinal fluid, or when a retinal detachment already exists in the patient’s fellow eye.
There is currently no medical therapy required for this condition.
Medical follow up
See above. Return and retinal detachment precautions should be carefully discussed with these patients, especially since many of them have concurrent myopia and lattice degeneration which increase the risk of a retinal detachment.
Surgical procedures (laserpexy) are rarely recommended for this condition. See above.
However, if there is documented progression of subretinal fluid around the hole, most retina specialists will recommend barricade laser.
When atrophic holes are the primary cause of macula off/ macula threatening retinal detachment in young, phakic patients without a posterior vitreous detachment present, scleral buckling may be preferred over vitrectomy.
Surgery (buckling or vitrectomy) should also be considered in retinal detachment approaching the arcade, though laser delimitation may also be an option.
The prognosis for atrophic retinal holes is good. There is a low risk of retinal detachments in patient with round holes, and the incidence of atrophic holes in the general population is low as well.
- Kanski, Jack. Clinical Ophthalmology 5th edition. Butterworth-Heinemann; 2003:359-371
- Preferred Practice Patterns: Posterior Vitreous Detachment, Retinal Breaks, and Lattice Degeneration. AAO 2008
- Byer N. Subclinical Retinal Detachment Resulting from Asymptomatic Retinal Breaks. Ophthalmology 2001; 108:1499-1504
- Gonzales C,Gupta A, Schwartz S,et al.The fellow eye of patients with phakic rhegmatogenous retinal detachment from atrophic holes of lattice degeneration without posterior vitreous detachment. Br J Ophthalmol 2004 88: 1400-1402
- Michaelson I. Role of a Distinctive Choroido-retinal Lesion in the Pathogenesis of Retinal Hole: A Clinical and Pathological Report. Br J Ophthalmol 1956 40: 527-535
- Sigelman J. Vitreous Base Classification of Retinal Tears: Clinical Application. Surv Ophthalmol 25:59-74, 1980 | 0 | 2 | 9 | 0 | 0 | 0 | 2 | 0.412606 | 2 | 1,688 |
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DESCRIPTIONColonoscopy is a visual examination of the lining of the colon (large intestine, large bowel) with a fiberoptic endoscope. It is inserted through the anus and rectum and advanced through the large intestine under direct vision, using the scope's optical system. Instruments and tools can be passed through the scope, for taking samples (biopsies). This procedure may be performed in the outpatient setting.
Flexible sigmoidoscopy is a visual examination of the rectum and lower colon called the sigmoid colon. A sigmoidoscope, long flexible tube with fiber optics, is passed through the anus and rectum into the sigmoid colon. Instruments and tools can be passed through the scope, for taking samples (biopsies). This procedure may be performed in the outpatient setting.
Virtual colonoscopy, also known as computed tomography (CT) colonography, is an imaging technique of the colon involving thin-section helical CT to generate high-resolution 2-dimensional axial images of the colon. Three-dimensional images, which resemble the endoluminal images obtained with conventional endoscopic colonoscopy, are then reconstructed off line. Virtual colonoscopy has been investigated as an alternative to conventional endoscopic colonoscopy, specifically as an alternative screening technique for colon cancer. While virtual colonoscopy requires a full bowel preparation, similar to conventional colonoscopy, no sedation is required, and the examination is less time consuming. However, gas insufflation of the intestine, which may be uncomfortable to the patient, and interpretation of the images is described as difficult and time consuming.
POLICYFor Coding Guidelines see the Monitored Anesthesia Care during Gastrointestinal Endoscopy Policy.
Screening (asymptomatic individuals) colonoscopy, fecal occult blood test (FOBT) and sigmoidoscopy will be allowed under the following guidelines:
Beginning at age 50, both men and women should follow ONE of the screening options below:
A digital rectal examination (DRE) should be performed at the time of EACH screening sigmoidoscopy or colonoscopy.High Risk
People should begin colorectal cancer screening earlier and/or undergo screening more often if they have any of the following colorectal cancer risk factors. Frequency should be determined by the ordering physician:
Inflammatory Bowel Disease
Most patients do not require colonoscopy for initial diagnosis, unless clinical sigmoidoscopy and radiological studies fail to secure diagnosis. Multiple biopsies are helpful when it is clinically necessary to distinguish between ulcerative colitis and Crohn's. Screening colonoscopy for follow-up of inflammatory bowel disease is usually not covered except for cancer surveillance in chronic ulcerative colitis.
Abnormal Exam (Symptomatic individuals)
Colonoscopy is considered medically necessary under the following circumstances:Unexplained bleeding
Flexible sigmoidoscopy in the ambulatory or office-setting is considered medically necessary under the following circumstances:
Computed tomography (CT) colonography, commonly referred to as virtual colonoscopy, may be considered medically necessary in patients for whom a conventional colonoscopy is indicated but who are unable to undergo conventional colonoscopy for medical reasons or in patients with an incomplete conventional colonoscopy because of colonic stenosis or obstruction.
Except as noted in the policy statement above, CT colonography is considered not medically necessary for the purposes of colon cancer screening because the clinical outcomes with this screening strategy have not been shown to be superior to other approaches including optical colonoscopy.
POLICY GUIDELINESInvestigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
Computed tomography (CT) colonography should be performed with a minimum 16-row detector CT scanner.
Contraindications to conventional colonoscopy may include continuous anticoagulation therapy or high anesthesia risk.
POLICY HISTORY2/1998: Approved by Medical Policy Advisory Committee (MPAC)
3/1999: Updated to reflect national standards
2/2001: Reviewed by MPAC; Virtual colonoscopy considered investigational. Healthy you guidelines will be aligned to be consistent with the American Cancer Society recommendations for early colorectal cancer detection.
5/23/2001: Code reference section revised; ICD-9 diagnosis code 235.2 and 239.0 deleted
11/14/2001: Colonoscopy and flexible sigmoidoscopy description revised under the "Description" section.
2/13/2002: Investigational definition added
3/20/2002: Revised verbiage of familial syndromes for clarity
3/26/2002: Healthy You guideline for barium enema deleted; G0121 added to non-covered
3/27/2002: Healthy You guidelines moved to Policy Exceptions
4/18/2002: Type of Service and Place of Service deleted
6/12/2002: ICD-9 diagnosis codes 235.2 and 239.0 added
7/23/2002: Policy section revised, Policy Exceptions deleted
7/30/2002: Prior authorization deleted
8/22/2002: CPT codes 44390-44397, 45332-45345, 45382-45387 deleted; ICD-9 procedure codes 45.42-45.43 deleted; ICD-9 diagnosis codes 555.9, 787.99, 799.8 deleted; ICD-9 diagnosis codes 557.1- 557.9 added; ICD-9 diagnosis code 564.89 description revised and one deleted; ICD-9 diagnosis code 556.9 is covered and non-covered depending on the description
12/11/2002: HCPCS G0102 added
11/18/2004: Reviewed by MPAC, CT colonography (“virtual colonoscopy”) remains investigational, policy title “Colonoscopy and Flexible Sigmoidoscopy” renamed “Colonoscopy, Flexible Sigmoidoscopy, and CT Colonography,” Description section updated to be consistent with BCBSA policy # 6.01.32, Sources updated
4/12/2005: Code Reference section updated, CPT code 44390, 44392, 44393, 44394, 45307, 45332, 45333, 45338, 45339, 45383, 45384, 45385 added covered codes, ICD-9 procedure code 45.42, 45.43, 98.03, 98.04 added covered codes, ICD-9 diagnosis 560.89 added covered codes, ICD-9 diagnosis codes 578.1 description revised covered codes, HCPCS G0102 deleted covered codes, HCPCS G0328 added covered codes, HCPCS 0066T, 0067T added non-covered codes, ICD-9 diagnosis code 556.9, 562.11, 562.13, 567.9, 569.49, 569.83, V72.83 deleted non-covered codes
3/13/2006: Coding updated. CPT4 2006 revisions added to policy
3/21/2006: Policy reviewed, no changes
09/13/2006: Coding updated. ICD9 2006 revisions added to policy
12/27/2006: Code Reference section updated per the 2007 CPT/HCPCS revisions
12/17/2007: Coding updated. CPT/HCPCS 2008 revisions added to policy
7/8/2008: Anesthesia Coding Policy hyperlink added
9/15/2008: Code reference section updated per the annual ICD-9 updates effective 10-1-2008
9/29/2009: Code reference section updated. New ICD-9 diagnosis code 569.71 added to covered table. HCPC code G0107 deleted from covered table due to code was deleted as of 12-31-06.
04/12/2010: Policy Statement revised to include CT Colonography may be considered medically necessary in patients with medical reasons. Code Reference Section updated revised to identify deleted codes S0605, 0066T and 0067T. Added new CPT Code 74261 and 74262 to the Covered Codes Table and CPT Code 74263 to Non-Covered Codes Table.
07/12/2012: Policy reviewed; no changes to policy statement. Removed S0605, 0066T, and 0067T from the Code Reference section as these codes have been deleted.
05/08/2013: Policy reviewed; no changes.
12/31/2014: Code Reference section updated to revise the description of the following CPT codes: 44388, 44390, 44392, 45330, 45332, 45333, 45378, 45379, 45384, and 45385. Effective 1/1/15. Added the following new 2015 CPT codes: 44401, 44402, 44403, 44404, 44405, 44406, 44407, 44408, 45346, 45347, 45349, 45350, 45388, 45389, 45390, 45393, 45398, and 45399. Added the following new 2015 HCPCS codes to the Code Reference section: G6019, G6020, G6022, G6023, G6024, G6025.
SOURCE(S)Hayes Medical Technology Directory
American Society of Gastroendoscopy (ASGE) consensus statement, "The Appropriate Use of Gastrointestinal Endoscopy"
Guidelines for Clinical Applications by the ASGE; Publication Nos. 1009 and 1013 1986.
United States Preventive Services Task Force (USPSTF) 1996 recommendation
American Cancer Society, Colon and Rectum Cancer Resource Center recommendations for early colorectal cancer detection
TEC Assessment Program, Volume 19, No. 6, July 2004
Blue Cross Blue Shield association policy #6.01.32
CODE REFERENCEThis is not intended to be a comprehensive list of codes. Note that some codes may be variable and coverage will be based on the clinical indication for the service.
For Coding Guidelines see the Anesthesia Coding Policy .
This may not be a comprehensive list of procedure codes applicable to this policy.
The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.
This may not be a comprehensive list of procedure codes applicable to this policy. | 0 | 4 | 16 | 8 | 0 | 9 | 2 | 0.620639 | 19 | 2,304 |
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