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Retinoblastoma Eye (retina cancer) Surgery   in India – Full information

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Retinoblastoma Eye Surgery  what causes retinoblastoma? Genetics of Retinoblastoma Symptoms Diagnosis Clinical PresentationInvestigationsEfficacy of chemo eductionTreatment Surgery Radiation therapy Cry therapy Laser therapy Chemotherapy Recurrent retinoblastoma Chemoprevention following vitrectomyChemotherapy for extra ocular retinoblastomaSide Effects of Cancer and Cancer Treatment After Treatment Risk Factors Conclusion Medical tourism / health tourism India

Retinoblastoma Eye Surgery 

Retinoblastoma (Rb) is a cancer of the retina. Retinoblastoma is the most common primary ocular malignancy of childhood. Although this disorder can occur at any age, it usually develops in young children. Most cases of retinoblastoma occur in only one eye, but both eyes can be affected. Untreated, retinoblastoma is almost always fatal, hence the importance of early diagnosis and treatment.

 Retinoblastoma is related to chromosome 13. Retinoblastoma occurs when a cell of the growing retina develops a mutation in the RB gene

(a tumor-suppressor gene). This mutation causes the cell to grow out of control and become cancerous.

 Mutations in the RB1 gene are inherited in an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to increase cancer risk. A person with retinoblastoma may inherit an altered copy of the gene from one parent, or the altered gene may be the result of a new mutation.

Retinoblastoma is the most common intraocular tumor in childhood. In majority of early stage retinoblastoma, the eyeballs as well as vision can be preserved with chemotherapy and local intraocular therapy with laser or photocoagulation. However, more than half the patients in India and other developing nations present in advanced stage of the disease. This article reviews the genetics, clinical approach, and treatment options for retinoblastoma focusing on advances in chemotherapy for intraocular retinoblastoma (chemo reduction), as well as improvement in survival in advanced retinoblastoma with surgery, chemotherapy, radiotherapy, and bone marrow transplantation.

 

What causes retinoblastoma?

In children with the genetic, i.e. the inheritable form of retinoblastoma, we know that there is something wrong with a small piece of the genetic material on chromosome 13, called the RB1 gene. Chromosomes contain the genetic codes which control the way cells grow and develop, and when a portion of the chromosome is missing

or one of the genetic codes is altered in some way, which is known as a mutation, a cancer may develop...

Genetics of Retinoblastoma

Retinoblastoma may occur as nonhereditary or hereditary tumor. Tumors in nonhereditary retinoblastoma (60% cases) are typically solitary and unilateral with no family history and no detectable chromosomal abnormalities. Although <10% of cases of retinoblastoma have a positive family history, about 40% of retinoblastoma are of hereditary origin caused by a germ line mutation in RB1 gene on chromosome 13q14. This is due to the majority being the result of a de novo mutation in the RB1 gene. Amongst those with hereditary retinoblastoma (40% cases), 25% cases have bilateral disease while 15% have unilateral disease. Hereditary RB1 mutations are found in all cells thereby increasing risk of other cancers, in particular, osteosarcoma and malignant melanoma.

Inherited retinoblastoma is transmitted as an autosomal dominant trait with high but incomplete pen trance. Children of patients with hereditary retinoblastoma have a one in two chance of carrying the germ cell mutation and for those who are carriers, the probability of developing retinoblastoma is very close to 90% if parents have bilateral retinoblastoma but probably less if they have the unilateral form.

The probability of developing retinoblastoma in off springs and siblings of patients is higher than in the general population because of which they need genetic counseling so as to effectively counsel and diagnose retinoblastoma early in high risk subjects. In bilateral cases or those with a positive family history, one can directly perform the genetic studies on peripheral blood sample as they would always be due to germ line mutation in RB1 gene. In unilateral cases and those with a negative family history, there is only 15%-20% chance that somatic cells would also carry the mutation. Therefore, in these cases, genetic studies for RB1 gene mutation are initially performed in the tumor specimen, and subsequently, once the mutation has been identified, peripheral blood is screened to determine if it is a germ line mutation (hereditary retinoblastoma) or non hereditary retinoblastoma.

If genetic testing is not pursued, then tumor surveillance for all siblings of the affected patient is recommended, which includes examination under anesthesia (EUA) at birth and every four months until the age of 4 years. On the contrary, if genetic testing demonstrates that the sibling did not inherit RB1 gene mutation, the surveillance and anesthesia required for eye examinations can be avoided, thereby decreasing costs and potential morbidity. Further, in unilateral retinoblastoma, if it can be demonstrated that the child does not carry a germ line RB1 gene mutation, then (a) the child is not at substantial risk for second malignancies; (b) radiation therapy is associated with less hazards and; (c) the parents and eventually the child have a negligible risk of having another child with retinoblastoma. 

Symptoms

Children with retinoblastoma often experience the following symptoms. Sometimes, children with retinoblastoma do not show any of these signs or symptoms. Or, these symptoms may be similar to symptoms of other medical conditions. If you are concerned about a symptom on this list, please talk to your child's doctor. Sometimes, a doctor finds retinoblastoma on a routine, well-baby examination. Most often, however, parents notice symptoms such as:

A pupil that looks white or red, instead of the normal black A crossed eye (looking either toward the ear or toward the

nose) Poor vision A red, painful-looking eye An enlarged pupil Different-colored irises

Diagnosis

Doctors use many tests to diagnose cancer and determine if it has metastasized (spread). Some tests may also determine which treatments may be the most effective. Although a biopsy is the only way to make a definitive diagnosis for most types of cancer, this is usually not possible in the case of retinoblastoma, and the doctor will suggest other ways to make a diagnosis. Imaging tests may be used

to find out whether the cancer has metastasized. Your doctor may consider these factors when choosing a diagnostic test:

Age and medical condition The type of cancer Severity of symptoms Previous test results

The next step after observing the symptoms is to have the child examined by a specialist, who will do a thorough ophthalmic examination to check the retina for a tumor. Depending on the age of the child, either a local or general anesthetic is used during the eye examination.

The specialist will make a drawing or take a photograph of the tumor in the eye to provide a record for future examinations and treatment, and may use additional tests to confirm or detect a tumor.

If a newborn has a family history of retinoblastoma, the baby should be examined shortly after birth by an ophthalmologist (a medical eye doctor) who specializes in cancers of the eye.

Clinical presentation

The median age of diagnosis is 2 years. Bilateral retinoblastoma occurs earlier than unilateral disease. Majority of retinoblastoma in developed nations presents as an intraocular disease wherein 90% of cases are curable. However, in the developing nations, still 65% of patients may present with extra ocular disease. An unpublished data from our center showed that mean age of presentation of unilateral retinoblastoma is 34 months, while that of bilateral disease is 24 months, which is higher than that in the west. The mean duration of symptoms was 8 months prior to visiting the tertiary care center, and 49% of patients presented with extra ocular disease. This may be due to the lack of awareness, delayed referrals, and/or more aggressive disease biology. From a therapeutic point of view, retinoblastoma presentation may be divided into the following subtypes:

A. Early stage intraocular disease (preservation of eye possible) presents most commonly with leucocoria (white reflex with an ophthalmoscope) followed by strabismus. Therefore, a pediatrician should always include the documentation of a red reflex with an

ophthalmoscope in examination of newborn and at subsequent well baby visits of a child. The absence of red reflex or strabismus merits an examination by an ophthalmologist in order to detect early stage intraocular retinoblastoma.

B. Advanced intraocular retinoblastoma (needs enucleation) presents with rubeosis iridize, hyphema, hypo yon, and glaucoma. The potential diagnosis of retinoblastoma should always be investigated in a child presenting with spontaneous hyphema in the absence of trauma or who presents with signs of endophthalmitis. Pain is not a feature of intraocular retinoblastoma unless secondary glaucoma or inflammation is present.

C. Extra ocular retinoblastoma presents with proptosis, preauricular lymphadenopathy, and bone pain, features suggestive of bone marrow or central nervous system involvement.

Investigations

The diagnostic work up include EUA of the eye and ultra sonography and CT scan of the orbit and head to confirm the diagnosis of retinoblastoma, and to detect entopic disease in the pineal gland. The clinical presentation and ancillary radiological findings are typical for retinoblastoma in majority of the patients, and a tissue biopsy is not required for confirmation prior to the therapy. However, a fine needle aspiration biopsy may be performed in select cases of pediatric ophthalmologic disease where the diagnosis is in question. Metastasis work up includes cerebrospinal fluid examination for malignant cells and bone marrow biopsy and bone scan in those with extra ocular disease. Intraocular retinoblastoma is traditionally classified by Reese-Ellsworth (RE) classification whereas intraocular and extra ocular retinoblastoma is classified according to Grabowski-Abramson staging

Efficacy of chemo eduction

An early volume reduction of around 50% after two courses of VEC can usually be expected. The overall salvage of eyes in the chemo reduction studies is about 80%. EBRT was added in an additional

30% of the salvaged eyes. Thus, approximately 50-60% of affected eyes treated with chemo reduction are successfully preserved with avoidance of EBRT or enucleation. The rate of globe preservation is best with less advanced eyes (85%), such as those in RE groups I to IV whereas with more advanced eyes, such as those in RE group V, preservation is less successful at <50%. In a study by Shields et al. chemo eduction using six cycles of VEC offers satisfactory retinoblastoma control for RE groups I-IV eyes, with treatment failure necessitating additional EBRT in only 10% of eyes and enucleation in 15% of eyes at 5-year follow-up. Patients with RE group V eyes required EBRT in 47% and enucleation in 53% at 5 years. Thus, all localized intraocular retinoblastoma have a potential for eye preservation using chemo reduction. However, any evidence for potential micrometastatic disease or overt metastasis disease should be excluded from chemo reduction

Treatment

Clinical trials are the standard of care for the treatment of children with cancer. In fact, more than 60% of children with cancer are treated as part of a clinical trial. Clinical trials are research studies that compare the standard treatments (the best treatments available) with newer treatments that may be more effective. Cancer in children is rare, so it can be hard for doctors to plan treatments unless they know what has been most effective in other children. Investigating new treatments involves careful monitoring using scientific methods and all participants are followed closely to track progress.

To take advantage of these newer treatments, all children with cancer should be treated at a specialized cancer center. Doctors at these centers have extensive experience in treating children with cancer and have access to the latest research. Many times, a team of doctors treats a child with cancer. Pediatric cancer centers often have extra support services for children and their families, such as nutritionists, social workers, and counselors. Special activities for children with cancer may also be available. Surgical treatment for retinoblastoma should also be performed by specially trained pediatric ophthalmologists.

Several types of therapies are used for retinoblastoma, and more than 90% of children can be cured. In addition to cure, an important goal of therapy for retinoblastoma is the preservation of vision. Many of these treatment approaches have become available as a result of clinical trials. The Children’s Oncology Group has recently developed treatment protocols for which some children with retinoblastoma will be eligible.

Treatments for retinoblastoma include:

Surgery

Surgery to remove the eye is called enucleation. Children with a tumor in one eye only can often be cured with this treatment. In children with a tumor in both eyes, enucleation is used only if the ocular oncologist determines that preserving vision using other treatment is not possible.

Radiation therapy

Radiation therapy uses high-energy x-rays or other particles to kill cancer cells. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation therapy given from a machine outside the body. Radioactive plaque therapy, also called internal radiation therapy, is the delivery of radiation therapy directly to the eye with a disc containing radiation.

Fatigue, drowsiness, nausea, vomiting, and headache are common temporary side effects of radiation therapy. Radiation therapy in young children can interfere with normal growth, including growth of the orbital bones, depending on the dose. The increased risk of additional tumors later in life for children with the hereditary form of retinoblastoma is further increased following radiation therapy. These effects are not seen after radioactive plaque therapy.

Cry therapy

Cry therapy uses extreme cold to destroy cancer cells.

Laser therapy

Laser therapy uses heat in the form of a laser to shrink smaller tumors. It may be called thermotherapy (or TTT for transpupillary thermotherapy), and it may be used alone or in addition to cry therapy or radiation therapy. Photocoagulation is a different type of laser therapy that uses light to shrink tumors.

Chemotherapy

Chemotherapy uses drugs to kill cancer cells, and may be used to shrink tumors in the eye. It is administered by a pediatric oncologist and often makes it possible to completely eliminate any remaining smaller tumors with the following focal (localized) measures:

Thermotherapy or photocoagulation (laser therapy) Cry therapy Radioactive plaque therapy

Chemo reduction is a treatment approach that is often used in children with bilateral disease in the hope of avoiding enucleation and preserving vision in at least one eye. The ophthalmologist, in consultation with the pediatric oncologist, will determine if this treatment is appropriate. Both doctors will monitor the response to

treatment regularly and may recommend additional treatment to prevent the cancer from returning.

The drugs used most often are incrusting (Oncovin), carboplatin (Paraplatin), and etoposide (VePesid, Etopophos, and Toposar). Depending on the extent of the tumor, a combination of two or more drugs will be recommended. All chemotherapy has side effects that occur during the period of treatment. Some drugs have the potential for specific long-term complications. Your doctor will discuss these before treatment begins.

The medications used to treat cancer are continually being evaluated. Talking with your child's doctor is often the best way to learn about the medications they've been prescribed, their purpose, and their potential side effects or interactions with other medications.

Recurrent retinoblastoma

Treatment of recurrent retinoblastoma depends on where the cancer recurred and how aggressive the new tumor is. The doctor may recommend surgery, radiation therapy, chemotherapy, or focal measures (photocoagulation, thermotherapy, or cry therapy).

Chemoprevention following vitrectomy

Retinoblastoma may present with atypical features such as vitreous hemorrhage or signs of vitreous inflammation, particularly in older children. Vitrectomy should be avoided in these cases until the possibility of underlying retinoblastoma is excluded. If vitrectomy is performed in an eye with unsuspected retinoblastoma, enucleation combined with chemotherapy, radiotherapy or both without delay is advised to prevent systemic tumor dissemination.

Chemotherapy for extra ocular retinoblastoma

Metastasis retinoblastoma is seen in less than 10% cases in developed nations whereas almost two-third of cases of retinoblastoma in developing countries. Chemotherapy is indicated in all these situations and is used in the following two fashions:

1. Conventional chemotherapy wherein the same drugs are used as

is used in chemo reduction or chemoprevention, but for a longer duration of 6-12 months.

2. High dose chemotherapy (HDT) wherein after initial conventional chemotherapy, the patient is consolidated with high doses of the same agents and bone marrow rescued with an autologous stem cell transplantation (ASCT).

Two different subgroups of patients with extra ocular retinoblastoma with different outcome can be distinguished as follows:

A. Extra ocular disease limited to orbit alone (invasion up to or beyond the cut end of optic nerve; sclera invasion up to the orbital contents) or with concomitant lymph node invasion. These patients have a 5-year progression free survival of >80% using initial exenteration followed by intensive chemotherapy and radiotherapy. Similar results have also been obtained using initial neoadjuvant chemotherapy followed by limited surgery (enucleation or resection of residual orbital mass) and adjuvant therapy and radiotherapy. Comparable results have been reported using HDT with ASCT. Thus, HDT in these two situations seems to be a therapeutic alternative with the advantage of shorter duration of therapy. Further, most of the failures or recurrences are in the CNS, and thus, intrathecal chemotherapy is used by some centers along with chemotherapy.

B. Those with systemic and/or CNS dissemination (bones, bone marrow, positive CSF cytology, or mass lesion in brain) are seldom cured with conventional chemotherapy. However, HDT using carboplatin, etoposide, and cyclophosphamide is effective in patients with chemo sensitive retinoblastoma patients with distant metastasis disease, except those with CNS disease. Prognosis is extremely poor in those with CNS disease. CNS irradiation, as is currently employed, does not cure CNS disease. Role of intrathecal therapy using methotrexate, cytosine arabinoside, and hydrocortisone, as is employed in CNS leukemia, is debatable. Thus, more effective therapeutic strategies are required to cure CNS disease in retinoblastoma.

Side Effects of Cancer and Cancer Treatment

Cancer and cancer treatment can cause a variety of side effects; some are easily controlled and others require specialized care. Below

are some of the side effects that are more common to retinoblastoma and its treatments.

Fatigue (tiredness). Fatigue is extreme exhaustion or tiredness, and is the most common problem that people with cancer experience. More than half of patients experience fatigue during chemotherapy or radiation therapy, and up to 70% of patients with advanced cancer experience fatigue. Patients who feel fatigue often say that even a small effort, such as walking across a room, can seem like too much. Fatigue can seriously impact family and other daily activities, can make patients avoid or skip cancer treatments, and may even impact the will to live.

Nausea and vomiting. Vomiting, also called emesis or throwing up, is the act of expelling the contents of the stomach through the mouth. It is a natural way for the body to rid itself of harmful substances. Nausea is the urge to vomit. Nausea and vomiting are common in patients receiving chemotherapy for cancer and in some patients receiving radiation therapy. Many patients with cancer say they fear nausea and vomiting more than any other side effects of treatment. When it is minor and treated quickly, nausea and vomiting can be quite uncomfortable but cause no serious problems. Persistent vomiting can cause dehydration, electrolyte imbalance, weight loss, depression, and avoidance of chemotherapy.

After Treatment

All children cured of cancer, including those with retinoblastoma, require life-long, follow-up care. Once a child has been free of retinoblastoma for two to four years following treatment, and is considered cured, the emphasis during periodic follow-up visits changes. Pediatric oncologists will focus on the quality of the child's life, including developmental and psychosocial concerns.

Most young children adapt well to the loss of one eye if enucleation took place. Rarely, both eyes will require removal to save the child's life. If both eyes are removed, the local educational system is required to provide special services. Parents are encouraged to investigate the school's services and advocate on their child's behalf.

Based on the therapy the child received and whether the child has the genetic form of retinoblastoma, the doctor will determine what

evaluations are needed to check for long-term effects. This may include imaging studies (CT scan or MRI) and blood work. Counseling will also be provided in the case of children who have an increased risk of additional tumors later in life, such as those with bilateral disease and those with unilateral disease who have a family history of the disease. Annual visits to specialized ophthalmologic and medical oncologists are necessary in order to fully monitor the child's recovery, and to increase the probability that a second cancer will be detected in its earliest stages.

Children who have had cancer can also enhance the quality of their future by following established guidelines for good health into and through adulthood, including not smoking, maintaining a healthy weight, and avoiding drinking alcohol in excess.

Risk Factors

A risk factor is anything that increases a person's chance of developing a disease, including cancer. There are risk factors that can be controlled, such as smoking, and risk factors that cannot be controlled, such as age and family history. Although risk factors can influence disease, for many risk factors it is not known whether they actually cause the disease directly. Some people with several risk factors never develop the disease, while others with no known risk factors do.

When retinoblastoma affects both eyes, it is always a genetic condition, even though only 10% to 15% of children with retinoblastoma have a family history of the disease. Rarely, the genetic form occurs in only one eye. The genetic form of the disease always occurs in younger children (rarely beyond one year old) and increases the child's risk of developing another cancer later in life. About 60% of children with retinoblastoma do not have the genetic form. They develop a single tumor in only one eye, and there is no increased risk of additional tumors later in life.

Children who have had bilateral retinoblastoma or the hereditary form of unilateral retinoblastoma are at increased risk for developing other types of cancer; the risk of additional tumors is higher in those children who receive radiation therapy to the orbit (eye socket) to preserve vision or to other parts of the body where the tumor has spread.

Conclusion

Retinoblastoma is a chemo sensitive disease but cannot be cured with chemotherapy alone. It is a very effective mode of therapy in preserving vision and the long-term complications of enucleation and EBRT, especially in intraocular retinoblastoma. Metastasis retinoblastoma to the orbit can be treated with good results with combination chemotherapy, radiotherapy, and possibly, conservative eye surgery as well. Distant metastasis disease cannot be cured with conventional chemotherapy in majority of the cases; however, HDT with ASCT appears to be a promising therapy for such cases. Retinoblastoma with CNS metastases continues to have dismal prognosis despite HDT with SCT and/or cranial radiation.

Medical tourism / health tourism India

India is one of the best places for the medical treatment or any other health care in India. Every year thousand of visitors are coming to India from around the world just for the medical check up and other type of cancer and cardiac surgery or others diseases. India is giving Thailand stiff competition in healthcare services for overseas patients with cost of surgery lower by over 30% and in fact cheapest in entire south Asia. Medical tourism in fast emerging as a big opportunity for India with its low cost advantage, high quality healthcare providers and an English speaking populace. Medical tourism has become a common form of vacationing, and covers a broad spectrum of medical services. Medical tourism mixes leisure, fun and relaxation together with wellness and healthcare.A combination of many factors has lead to the recent increase in popularity of medical tourism. Exorbitant cost of healthcare and medical facilities in advanced countries, ease and affordability of international travel, favorable currency exchange rates in the global economy, rapidly improving technology and high standards of medical care in the developing countries has all contributed their share to this rapid development of medical tourism. India has originated as one of the most important hubs for medical tourism. Many people from the developed countries come to India for the rejuvenation promised by yoga and Ayurvedic massage however, a nice blend of top-class medical expertise at attractive prices is helping more and more Indian corporate hospitals to lure foreign patients, including patients from developed nations such as the UK

and the US, for high end surgeries like Cardiac By Pass Surgery or the various cancer surgeries. As more and more patients from Europe, the USA and other affluent nations with high medical costs look for effective options, healthcare tourism in India is definitely on the cards for most of them and the fast growing Indian corporate health sector is fully geared to meet that need.

Not just cost savings or the high standard of medical care facility, but also the waiting time is much lower for any treatment in India than in any other country. Medical help is often an emergency and situations can turn worse if the treatment is delayed. While you might have to wait for several months to get a surgical operation done in the US, in India things can be arranged within a week. For further details on the Retinoblastoma Eye (retina cancer) Surgery   in India at an economic cost feel free to visit us at www.indiancancersurgerysite.com  or mail your queries at info@indiancancersurgerysite.com or talk to us at +91 9579034639.