A congenital condition Situs inversus

Situs inversus (also called situs transversus or oppositus) is a congenital condition in which the major visceral organs are reversed or mirrored from their normal positions. The normal arrangement of internal organs is known as situs solitus while situs inversus is generally the mirror image of situs solitus. Although cardiac problems are more common than in the general population, most people with situs inversus have no medical symptoms or complications resulting from the condition, and until the advent of modern medicine it was usually undiagnosed.

Epidemiology

Situs inversus is found in about 0.01% of the population or about 1 person in 10,000.

 In the most common situation, situs inversus totalis, it involves complete transposition (right to left reversal) of all of the abdominal organs.

The heart is not in its usual position in the left chest, but is on the right, a condition known as dextrocardia (literally, right-hearted). Because the relationship between the organs is not changed, most people with situs inversus have no medical symptoms or complications.

    In rarer cases such as situs ambiguus or heterotaxy, situs cannot be determined. In these patients, the liver may be midline, the spleen absent or multiple, and the bowel malrotated. Often, structures are duplicated or absent altogether. This is more likely to cause medical problems than situs inversus totalis.

Signs and symptoms

In the absence of congenital heart defects, individuals with situs inversus are phenotypically normal, and can live normal healthy lives, without any complications related to their medical condition.

    There is a 5–10% prevalence of congenital heart disease in individuals with situs inversus totalis, most commonly transposition of the great vessels. The incidence of congenital heart disease is 95% in situs inversus with levocardia.

Many people with situs inversus totalis are unaware of their unusual anatomy until they seek medical attention for an unrelated condition, such as a rib fracture or a bout of appendicitis. The condition may also be discovered during the administration of certain medicines or during tests such as a barium meal or enema. The reversal of the organs may then lead to some confusion, as many signs and symptoms will be on the atypical side. For example, if an individual with situs inversus develops appendicitis, they will present to the physician with lower left abdominal pain, since that is where their appendix lies. Thus, in the event of a medical problem, the knowledge that the individual has situs inversus can expedite diagnosis. People with this rare condition should inform their doctors before an examination, so the doctor can redirect their search for heart sounds and other signs. Wearing a medical identification tag can help inform health care providers in the event the person is unable to communicate.

Cause

Situs inversus has an autosomal recessive pattern of inheritance.

Situs inversus is generally an autosomal recessive genetic condition, although it can be X-linked or found in identical "mirror image" twins.

About 25% of individuals with situs inversus have an underlying condition known as primary ciliary dyskinesia (PCD). PCD is a dysfunction of the cilia that manifests itself during the embryologic phase of development. Normally functioning cilia determine the position of the internal organs during early embryological development, and so embryos with PCD have a 50% chance of developing situs inversus. If they do, they are said to have Kartagener syndrome, characterized by the triad of situs inversus, chronic sinusitis, and bronchiectasis. Cilia are also responsible for clearing mucus from the lung, and the dysfunction causes increased susceptibility to lung infections. Kartagener syndrome can also manifest with male infertility as functional cilia are required for proper sperm flagella function.

Effect on anatomy

If the heart is swapped to the right side of the thorax, it is known as "situs inversus with dextrocardia" or "situs inversus totalis". If the heart remains on the normal left side of the thorax, a much rarer condition (1 in 2,000,000 of the general population), it is known as "situs inversus with levocardia" or "situs inversus incompletus".

.

Diagnosis

Diagnosis of situs inversus can be made using common radiographic imaging techniques such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI).

Treatment

No treatment needed, as the subject is otherwise healthy.

History

Dextrocardia (the heart being located on the right side of the thorax) was first seen and drawn by Leonardo da Vinci in 1452–1519, and then recognised by Marco Aurelio Severino in 1643. However, situs inversus was first described more than a century later by Matthew Baillie

Statistics about Situs Inversus

1. Up to 5% of people with Situs Inversus have a functional heart defect, which is up to five times greater than the general population rate.

2. The amount of births that occur with Situs Inversus that have the underlying condition of Primary Ciliary Dyskinesia [PCD]: 1 in 4.

3. In the United States, the chances of having a child born with Situs Inversus is just 1 in 10,000.

4. 4 out of 5 people who have Situs Inversus also have a right-sided aortic arch.

5. The percentage of people who have cogenital heart disease with Situs Inversus: up to 10%.

6. When levocardia is present, the incidence of congenital heart disease climbs to 95%.

7. The dextrocardia version of Situs Inversus was first seen and documented by Leonardo da Vinci, but wasn’t recognized until 1643.

8. Levocardia occurs in only 1 in 22,000 births.

09. When PCD is present in embryos, the chances of Situs Inversus happening are 1 in 2.

10. 20% of people who are born with Situs Inversus have Kartagener Syndrome, but 50% of those with the syndrome have Situs Inversus.

11. Life expectancy rates with Situs Inversus are similar to that of the general population.

12. When marriages occur between people who are descended from the same direct ancestor, the incident rates of Situs Inversus tend to trend higher.

13. COPD rates and other breathing issues, including asthma, are slightly higher in cases of Situs Inversus than with the general population.

14. People with Situs Inversus have a higher than average risk to develop bronchiectasis, pneumonia, conductive deafness, and communicating hydrocephalus.

  There is a third version of Situs Inversus that sometimes occurs, but it is often called Situs Ambiguous instead. This is because there are several organs that are displaced from their regular location in the body, but the distribution is randomized instead of clearly defined. Some doctors do not consider this to be a case of Situs Inversus because there is no inversion. Instead of having the right lung on the left, the ambiguous version might provide two right lungs instead.

It is believed that many factors are involved in the development of Situs Inversus, but the cause doesn’t have a definite reason behind it. It is also believed that there is at least one gene that helps to contribute to the formation of Situs Inversus. That is because it is known to run in families, although it is just as likely to happen in an isolated fashion as it is to occur in families that have a history of it. Although organ issues, especially cardiac functions, can be disrupted in children born with this condition, it is also possible for children to have no complications at all.

Living with Situs Inversus

It is very possible to have Situs Inversus and live a very normal, fulfilling life. Writers, actresses, and professional athletes have all been diagnosed with this condition and have not had any complications to note.

The most important aspect of living with Situs Inversus is to let medical professionals know that this condition exists. Because it is so rare, doctors simply assume that the human body they are examining has been created correctly.

The goal of living with Situs Inversus is to simply treat the symptoms as they occur. The most common issues are the development of sinus infections and other items that can be treated with basic antibiotics. Surgery is rarely an option for people with this condition because there is often no way to correct the situation. It is an instance where two wrongs really do end up making a right.

PCD primary Ciliary dyskinesia

The main consequence of impaired ciliary function is reduced or absent mucus clearance from the lungs, and susceptibility to chronic recurrent respiratory infections, including sinusitis, bronchitis, pneumonia, and otitis media. Progressive damage to the respiratory system is common, including progressive bronchiectasis beginning in early childhood, and sinus disease (sometimes becoming severe in adults). However, diagnosis is often missed early in life despite the characteristic signs and symptoms. In males, immotility of sperm can lead to infertility, although conception remains possible through the use of in vitro fertilization, there also are reported cases where sperm were able to move. Trials have also shown that there is a marked reduction in fertility in female sufferers of Kartagener's Syndrome due to dysfunction of the oviductal cilia.

Many affected individuals experience hearing loss and show symptoms of otitis media which demonstrates variable responsiveness to the insertion of myringotomy tubes or grommets. Some patients have a poor sense of smell, which is believed to accompany high mucus production in the sinuses (although others report normal - or even acute - sensitivity to smell and taste). Clinical progression of the disease is variable, with lung transplantation required in severe cases. Susceptibility to infections can be drastically reduced by an early diagnosis. Treatment with various chest physiotherapy techniques has been observed to reduce the incidence of lung infection and to slow the progression of bronchiectasis dramatically. Aggressive treatment of sinus disease beginning at an early age is believed to slow long-term sinus damage (although this has not yet been adequately documented). Aggressive measures to enhance clearance of mucus, prevent respiratory infections, and treat bacterial superinfections have been observed to slow lung-disease progression. Although the true incidence of the disease is unknown, it is estimated to be 1 in 32,000, although the actual incidence may be as high as 1 in 15,000

Fibroadenoma Breast

          Fibroadenomas, are benign breast tumours characterized by an admixture of stromal and epithelial tissue. Breasts are made of lobules (milk producing glands) and ducts (tubes that carry the milk to the nipple). These are surrounded by glandular, fibrous and fatty tissues. Fibroadenomas develop from the lobules. The glandular tissue and ducts grow over the lobule to form a solid lump.

Since both fibroadenomas, and breast lumps as a sign of breast cancer can appear similar, it is recommended to perform ultrasound analyses and possibly tissue sampling with subsequent histopathologic analysis in order to make a proper diagnosis. Unlike typical lumps from breast cancer, fibroadenomas are easy to move, with clearly defined edges. Fibroadenomas are sometimes called breast mice or a breast mouse owing to their high mobility in the breast

Signs and symptoms

Fibroadenomas are benign (not harmful in effect) tumours of the breast, most often present in women in their 20s and 30s. Clinically, fibroadenomas are usually solid breast lumps that are:

• Painless

• Firm or rubbery

• Mobile

• Solitary-round with distinct, smooth borders

• Found in either one or both breasts

Cause

     The cause of fibroadenoma is unknown (idiopathic). A connection between fibroadenomas and reproductive hormones has been suggested which may explain why they present themselves during reproductive years, increase in size during pregnancy, and regress post-menopause.

Higher intake of fruits and vegetables, higher number of live births, lower use of oral contraceptives and moderate exercise are associated with lower frequency of fibroadenomas.

Cytology

The diagnostic findings on needle biopsy consist of abundant stromal cells, which appear as bare bipolar nuclei, throughout the aspirate; sheets of fairly uniform-size epithelial cells that are typically arranged in either an antler-like pattern or a honeycomb pattern. These epithelial sheets tend to show typical metachromatic blue on Diff-Quik staining. Foam cells and apocrine cells may also be seen, although these are less diagnostic features. The gallery images below demonstrate these features..

Macroscopic

Approximately 90% of fibroadenomas are less than 3 cm in diameter. However, these tumors have the potential to grow reaching a remarkable size, particularly in young individuals. The tumor is round or ovoid, elastic, and nodular, and has a smooth surface. The cut surface usually appears homogenous and firm, and is grey-white or tan in colour. The pericanalicular type (hard) has a whorly appearance with a complete capsule, while the intracanalicular type (soft) has an incomplete capsule.

Fibroadenoma of the breast is a benign tumor composed of a biphasic proliferation of both stromal and epithelial components that can be arranged in two growth patterns: pericanalicular (stromal proliferation around epithelial structures) and intracanalicular (stromal proliferation compressing the epithelial structures into clefts).

These tumors characteristically display hypovascular stroma compared to malignant neoplasms. Furthermore, the epithelial proliferation appears in a single terminal ductal unit and describes duct-like spaces surrounded by a fibroblastic stroma. The basement membrane is intact.

Treatment

Fibroadenomas can be expected to shrink naturally and so, most are simply monitored. Monitoring fibroadenomas involves regular check-ups to make sure that the breast mass is not growing and is not potentially cancerous. Check-ups involve physical examinations performed every 3–6 months and optional diagnostic imaging performed every 6–12 months for 1–2 years. Generally, surgery is only recommended if the fibroadenoma gets larger or causes increased symptoms. They are removed with a small margin of normal breast tissue if the preoperative clinical investigations are suggestive of the necessity of this procedure. A small amount of normal tissue must be removed in case the lesion turns out to be a phyllodes tumour on microscopic examination.

Some fibroadenomas respond to treatment with ormeloxifene.

Fibroadenomas have not been shown to recur following complete excision or transform into phyllodes tumours following partial or incomplete excision.

Non-invasive Surgical Interventions

There are several non-invasive options for the treatment of fibroadenomas, including percutaneous radiofrequency ablation (RFA), cryoablation, and percutaneous microwave ablation. With the use of advanced medical imaging, these procedures do not require invasive surgery and have the potential for enhanced cosmetic results compared with conventional surgery.

Cryoablation

The FDA approved cryoablation of a fibroadenoma as a safe, effective, and minimally-invasive alternative to open surgical removal in 2001. During cryoablation, ultrasound imaging is used to guide a probe into the mass of breast tissue. Extremely cold temperatures are then used to destroy the abnormal cells, and over time the cells are reabsorbed into the body. The procedure can be performed as an outpatient surgery using local anesthesia, and leaves substantially less scarring than open surgical procedures and no breast tissue deformation.

The American Society of Breast Surgeons recommends the following criteria to establish a patient as a candidate for cryoablation of a fibroadenoma:

1.       The lesion must be sonographically visible.

2.       The diagnosis of a fibroadenoma must be confirmed histologically.

3.       The lesion should be less than 4 cm in diameter.

High Intensity Focused Ultrasound

Epidemiology

Of all breast tissue samples taken, fibroadenomas comprise about 50%, and this rate rises to 75% for tissue sample in women under the age of 20 years. Fibroadenomas are more frequent among women in higher socioeconomic classes and darker-skinned people. Body mass index and the number of full-term pregnancies were found to have a negative correlation with the risk of fibroadenomas. There are no known genetic factors that influence the rate of fibroadenomas. The rate of occurrence of fibroadenomas in women have been reported in literature to range from 7% to 13%.

A fibroadenoma is a very common benign (not cancer) breast condition. The most common symptom is a lump in the breast which usually moves when you touch it.

Fibroadenomas often develop during puberty so are mostly found in young women, but they can occur in women of any age. Men can also get fibroadenomas, but this is very rare.   

Symptoms of fibroadenoma

A fibroadenoma is usually felt as a lump in the breast which has a rubbery texture, is smooth to the touch and moves easily under the skin.

Fibroadenomas are usually painless, but sometimes they may feel tender or even painful, particularly just before a period.

Types of fibroadenoma

1.     Simple fibroadenoma

Most fibroadenomas are about 1–3cm in size and are called simple fibroadenomas. When looked at under a microscope, simple fibroadenomas will look the same all over. Simple fibroadenomas don’t increase the risk of developing breast cancer in the future.

2.     Complex fibroadenoma

Some fibroadenomas are called complex fibroadenomas. When these are looked at under a microscope, some of the cells have different features.

Having a complex fibroadenoma can very slightly increase the risk of developing breast cancer in the future.

3.     Giant or juvenile fibroadenoma

Occasionally, a fibroadenoma can grow to more than 5cm and may be called a giant fibroadenoma. Those found in teenage girls may be called juvenile fibroadenomas.

Causes

It’s not known what causes a fibroadenoma. It’s thought that it probably occurs because of increased sensitivity to the hormone oestrogen.

Breasts are made up of lobules (milk-producing glands) and ducts (tubes that carry milk to the nipple). These are surrounded by glandular, fibrous and fatty tissue.

Fibroadenomas develop from a lobule. The glandular tissue and ducts grow over the lobule and form a solid lump.

Diagnosis

If you find a breast lump, see your GP (local doctor). They’re likely to refer you to a breast clinic where you’ll be seen by specialist doctors or nurses.

At the breast clinic you’ll have various investigations, known as ‘triple assessment’, to help make a definite diagnosis. This assessment consists of:

•        a breast examination

•        ultrasound scan (uses high frequency sound waves to produce an image) and/or a mammogram (breast x-ray)

•        a core biopsy and/or a fine needle aspiration (FNA).

Fibroadenomas are often easier to identify in younger women. If you’re in your early 20s or younger, your fibroadenoma may be diagnosed with a breast examination and ultrasound only. However, if there’s any uncertainty about the diagnosis, a core biopsy or FNA will be done.

If you’re under 40, you’re more likely to have an ultrasound than a mammogram. Younger women’s breast tissue can be dense which can make the x-ray image less clear so normal changes or benign breast conditions can be harder to identify. However, for some women under 40, mammograms may still be needed to complete the assessment.

Surgery

Sometimes an operation called an excision biopsy is needed to remove a fibroadenoma if it’s a large, complex or juvenile fibroadenoma. You can also ask to have a fibroadenoma removed.

This may be done using a local or general anaesthetic.

Your surgeon may use dissolvable stitches placed under the skin which won’t need to be removed. However, if a non-dissolvable type is used, they will need to be taken out a few days after surgery. You’ll be given information about this and about looking after the wound before you leave the hospital.

Vacuum assisted excision biopsy

You may be offered a vacuum assisted excision biopsy to remove the fibroadenoma. This is a way of removing small fibroadenomas under local anaesthetic, without having surgery.

After an injection of local anaesthetic, a small cut is made in the skin. A hollow probe connected to a vacuum device is placed through this. Using an ultrasound or mammogram as a guide, the fibroadenoma is sucked through the probe by the vacuum into a collecting chamber. The biopsy device is used in this way until all of the fibroadenoma has been removed. This may mean that an operation under a general anaesthetic can be avoided. The tissue removed is sent to a laboratory and examined under a microscope. This procedure can cause some bruising and pain for a few days afterwards.