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��ࡱ�>��	MP����L�������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������[�	��-.bjbj����	4Nΐΐ&+���������=====����QQQ8�T�,Q\"0		����!�!�!�!�!�!�!$�#�.&<"=�����"=="�����==�!���!��:K,��������{�Qb|w
�!,"0\"�Rj&��j&�j&=����������""����\"������������������������������������������������������������������������j&����������	:	Challenges of managing advanced Retinoblastoma in a 4 year old Nigerian girl

Abstract
Retinoblastoma is the commonest childhood ocular malignancy. Advances in management of retinoblastoma make it possible to save life and vision in many patients. It is of interest in Sub-Saharan Africa however; management is marred by challenges including poverty and late presentation. This was a case report of advanced right eye retinoblastoma in a four year old girl. The Patient had modified exenteration and was booked for cytotoxic therapy within two weeks of surgery. The patient only returned to eye clinic four months later and after the tumour had reccurred. The cytotoxic therapy was commenced immediately and had four courses at monthly interval. The tumour regressed one month after the third course however; patient again defaulted from further follow up after the fourth course due to lack of fund. Health education of children�s caregivers, availability of resource for eye care and subsidized care for retinoblastoma are underscored.
Key words: Advanced Retinoblastoma, childhood cancer, cytotoxic therapy, lack of follow up.









Introduction 
Retinoblastoma is the commonest malignant intraocular tumour among children accounting for 3% of all cancer cases in developed countries1. In developing countries, the diagnosis is often late and patients are seen at advanced metastatic disease2-4  leading to high mortality rate1.
Chemotherapy has been shown to improve the survival rate of patients with advanced retinoblastoma using Vincristie, Etoposide and Carboplatin (VEC). 
There are peculiar challenges in managing tumours in developing countries mainly ignorance, poverty, late presentation and lack of follow up 5, 6. This was a case report of a four year old girl with advanced retinoblastoma who presented with management challenges. 











Case report
A case report of a four year old girl who presented in our clinic on account of three months history of right eye (RE) cat eye reflex, progressive protrusion, tearing, eye discharge and vision loss. The initial treatment comprised medicine store recommended eye drops and traditional eye medication, both without any improvement. The child was a product of a consanguineous marriage with no family history of similar problem among her siblings.
Examination at presentation revealed a normal general clinical condition. The visual acuities were nil light perception (NPL) RE and 6/9 left eye (LE). The LE was essentially normal. RE had marked proptosis with conjunctival hyperemia, chemosis and exposure keratopathy. Patient was admitted and subsequently reviewed by the Paediatrician. The patient�s haematological parameters were within normal limits. Ocular Ultrasound suggested advanced retinoblastoma with features of optic nerve involvement.
The patient eventually had modified exenteration RE within five days of admission. Patient was subsequently discharged home on request to return for follow up within two weeks when the histology report would have been ready and to commence cytotoxic therapy. Histology report confirmed poorly differentiated retinoblastoma RE.
Patient only reported back in our eye clinic four months after discharge with recurred tumour (Figure 1). The patient was re-admitted and co-managed with Paediatricians. Rehydration and allopurinol were commenced having found that haematological and electrolyte, urea and creatinine were essentially normal. Patient had first course of cytotoxics commenced within one week of re-admission using the regimen of intravenous (IV) Vincristine 0.05 mg/kg day 1, IV Carboplatin 18.6 mg/kg day 1 and IV Etoposide 5 mg/kg day 1 and 2. Patient had two other courses of cytotoxics at monthly intervals using the same regimen/protocol as in the first course. The swelling regressed one month after the last course (Figure 2). Parents again defaulted from bringing the patient for subsequent follow ups due to lack of funds.
	
Discussion 
The initial challenge was that of late presentation to the hospital which accounted for the advanced disease (orbital involvement) at the time of the diagnosis. The delay at presentation and diagnosis could be due to the patient movement from one medicine store to the other and to the application of traditional medications. It could also be due lack of knowledge of parents and health workers about the early signs of the disease since the initial symptom was that of cat eye reflex noticed in the right eye three months prior to presentation. Several studies have demonstrated that orbital extension is due to late presentation and diagnosis2-4. In developed countries diagnosis is often made at about 24-25 months of age as against 50 months and above in developing countries1, 7, 8. 
Another challenge faced in the management of this patient was poor compliance to follow up schedule. Patient was discharged home on request to return for follow up after two weeks when the histology report would have been ready. It is of note that having to wait for at least two weeks to get the histology report is an added challenge. The need to commence cytotoxic therapy was discussed with the parents before discharge; however, patient was brought back four months after the initial surgical intervention. By this time patient already had a re-growth of the tumour involving the right orbit and the upper eyelid. Mainly poverty among other factors contributed to this since parents bore the direct and indirect cost of managing this patient. The parents were in the low socio-economic cadre of the society. In our hospital, most patients bear their hospital fee and fee waiver is enjoyed by selected few very indigent patients. Such patient�s fee is bore by social welfare fund. However, in some countries there are social security systems that help cushion the effects for needy patients1. Aside our patient being poor, the observed poor compliance to follow up schedule might be related to the societal perception of cancer as an incurable deadly condition. Once they are informed of cancer as the diagnosis many would choose to go home than waste their scarce resources in the hospital5.
There were also challenges associated with the procurement of the drugs. The current combination chemotherapy for retinoblastoma is expensive and not readily available in our environment, even though it is highly effective as demonstrated in this case report, the regression of the re-growth after three courses. The cost and unavailability of the drugs in our environment added to the challenge of effective management of retinoblastoma. The cytotoxics used in this patient was procured from a pharmacy store in a city located about 700 kilometres away from our hospital. The local pharmacy outlets hardly stock current anti-cancer drugs since they are not routinely prescribed for patients to purchase, instead they prefer to stock drugs with very high turnover rates.
Even though the tumour appears to have regressed in this patient, the need for the patient to have more cytotoxics courses was discussed with the parents however; the parents defaulted from bringing the child for further follow up citing financial constraint as the reason for the default. This attitude of lack of follow up makes it difficult to have statistics on long term follow up of survivors. Medical Social services department of the hospital was contacted for assistance at some point during the course of managing this patient but could not render financial assistance due to lack of fund.
There is also the challenge of co-ordination and standardized protocol for managing retinoblastoma. This can be overcome through training of staff in the management of retinoblastoma. There is the need to train ocular oncologist as is the practice elsewhere. This would ultimately lead to increase survival rate of patients having retinoblastoma as the mortality rate among the patients is still very high in developing countries3,4.
Measures that can be adopted to ensure effective treatment of retinoblastoma in developing countries would include proper health education of staff and families on retinoblastoma and their managements as well as the establishment of retinoblastoma centres with collaborative efforts to co-ordinate and subsidize the treatment of retinoblastoma in our environment.




References 
Togo B, Sylla F, Traore F, Sylla M, Dicko-Traore F, Sidibe T, Diakite A, Keita MM. A 30-month prospective study on the treatment of retinoblastoma in the Gabriel Toure Teaching Hospital, Mali. Br J Ophthalmol 2010; 94: 467-469.
Antonell CHG, Steinhorst F, Filbeiro KB. Extraocular retinoblastoma: a 13year experience. Cancer 2003; 98: 1292-5.
Erwenne C, Franco E. Age and lateness of referral as determinants of extraocular retinoblastoma. Ophthalmic Paediatric Genetics 1989; 10:179-84.
Lawan A, Malami S. Clinico-pathological pattern and management of retinoblastoma in Kano, Nigeria. Ann Afr Med 2011; 10: 214-9.
Chirdan LB, Bode TF,Chirdan OO. Childhood cancers: challenges and strategies for management in developing countries. Afr J Paediatric Surg 2009; 6:126-30.
 Bekibele CO, Ayede AL, Asaolu OO, Brown BJ. Retinoblastoma: the challenges of management in Ibadan, Nigeria. J Paediatric Haematol Oncol 2009; 31: 552-5.
MacCarthy A, Birch JM, Draper GJ. Retinoblastoma: treatment and survival in Great Britain 1963-2002. Br J Ophthalmol 2009; 93: 38-9.
Broaddus E, Tophan A, Singh AD. Survival with retinoblastoma in the United States 1975- 2004. Br J Ophthalmol 2009; 93: 24-7.








Figure 1: Right eye recurrent tumour at four months after modified exenteration























Figure 2: Regressed right eye re-growth a month after the third course of chemotherapy









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