PROF. ABINYA NICHOLAS A O

Glivec is a drug used in the treatment of chronic myeloid leukaemia (CML) and
gastrointestinal stromal tumours (GISI). It is an expensive drug which would be
out of reach for most patients in Kenya. Norvatis Pharmaceutical together with
Axios International a healthcare management company and Max Foundation have made
it possible for patients in developing countries to get access to the drug at no
cost. Patients meet the cost of the confirmatory test and are recruited into the
programme to receive the drug at no cost. A total of 201 patients are in the
programme in Nairobi, mainly drawn from Kenyatta National Hospital the major
referral hospital in Kenya. The age range is nine years to 75 years with a mean
age of 39.5 years. Males make up 56.5% while females are 43.5%. CML are 173 (86%)
while GIST patients are 28 (13.9%). Most of the CML cases are referred in the
chronic stable phase (87.8%) and 85.7% have been on hydroxyurea as the initial
treatment. Compliance rates are approximately 80%

Given that oesophageal cancer (OC) is common in Malawi and its outcome is so
dismal, would it be pragmatic to promptly mitigate the effects of smoking,
alcohol and aflatoxins rather than seek a higher degree of local evidence for
their role in OC? We retrospectively analysed a total of 13,217 OC and Kaposi's
sarcoma (KS) cases as recorded in the Malawi National Cancer Registry from 1985
to February, 2006. We found no OC clustering to suggest a role for culturally
variable habits like smoking, alcohol, maize use and maize storage in the
country. It may be that drinking and eating hot foods physically damages the
oesophageal mucosa, this is in line with work recently reported from Asia. We
also found that OC numbers have risen in line with KS (and HIV) suggesting a link
between these conditions

Cancer is causing a lot of suffering and death in Africa but is not considered a
major health problem in Africa. This needs to change. Cancer should be given
equal emphasis to HIV/AIDS, tuberculosis (TB) and Malaria. A national cancer
policy is required in Malawi to develop and improve evidence-based cancer
prevention, early diagnosis, curative and palliative therapy. A national cancer
policy is crucial to ensure a priotised, clear, coordinated and sustained fight
against cancer. When no policy exists, events are likely to be random,
stakeholders and practitioners in the fight against cancer may not agree on how
to proceed, may duplicate efforts or may neglect areas that would have greater
nationwide impact resulting in poor quality activities and haphazard development.

OBJECTIVE: To evaluate chemotherapy induced myelosuppression, its management and
outcome.
DESIGN: Retrospective analysis of patients aged 13 years and above.
SETTING: Hurlingham Oncology Clinic and the Nairobi Hospital during the period of
June 1998 to June 2003.
SUBJECTS: Two hundred and two solid tumour and lymphoma patients treated with
pulsed chemotherapy at Hurlingham Oncology Clinic and those treated by the same
service at the Nairobi Hospital.
RESULTS: Two hundred patients were evaluable for nadir blood counts. World Health
Organisation (WHO) grade 3 neutropaenia complicated 57 (26.1%), and grade 4
complicated 56 (25.7%) treatments. Grade 0 neutropaenia was seen in 40 (18.4%)
treatments, 33 having included prophylactic Granulocyte-Colony Stimulating
Factors (G-CSF). Neutropaenia was worst following the first and sixth courses,
and repeated second line courses but the difference was not statistically
significant (p = 0.154). Fever complicated 6 grade 3 and 21 grade 4 neutropenic
episodes (23.1% of 117 evaluable). Twenty eight patients were hospitalised
because of severe neutropaenia (23 febrile, and five afebrile initially but with
absolute neutrophil counts < 0.01 x 10(9)/litre). Eight of them died, six
attributable to infections (21.4% mortality) and two attributed to other causes.
Median time to neutrophil recovery to 21.5 x 10(9)/litre was three days with a
mean of 4.6 days. Anaemia and thrombocytopaenia were not commonly experienced.
CONCLUSION: Prophylactic use of G-CSF may have prevented severe neutropaenia and
its use in severe neutropaenia may have reduced the duration and severity of
neutropaenia but the mortality rate for febrile neutropaenia remained high.

OBJECTIVE: To re-evaluate clinico-pathologic categorisation of patients with
Hodgkin's lymphoma, treatments offered and their appropriateness, and outcome of
this disease at Kenyatta National Hospital in the 1990s.
DESIGN: Retrospective survey of Hodgkin's lymphoma patients aged 13 years and
above at the Kenyatta National Hospital.
SETTING: Kenyatta National Hospital, Nairobi, Kenya.
SUBJECTS: Patients aged 13 years and above, with diagnosis of Hodgkin's lymphoma.
RESULTS: There were 75 males and 36 females. One case had no clear gender
details. 14.2% of the cases were of lymphocyte predominant histologic subtype,
23.6% nodular sclerosis, 26.4% mixed cellularity and 17% Lymphocyte depletion
(Rye Modification of Lukes and Butler Classification). Disease stages IIIB, IVA
and IVB (Ann Arbor) were found in 24.5% of the cases. The majority of the
patients (60.3%) were treated with the COPP protocol and 17% with ABVD. Complete
remission was realised in 56% of the cases and most cases were lost to follow-up,
making it difficult to correlate survival with known prognostic parameters, apart
from early stage disease and attainment of complete remission which correlated
with prolonged durations of follow-up.
CONCLUSION: The patients had earlier stage diseases than in earlier studies
locally, the histologic classification is still wanting, and the COPP protocol
appeared still popular instead of being abandoned. Response rates were lower than
expected and losses to follow-up made it difficult to properly evaluate
prognostic parameters. Early disease stage and attainment of complete remission
appeared to correlate with longer follow-up duration.

OBJECTIVES: To determine the clinico-pathologic and prognostic factors, treatment
and outcome of non-Hodgkin's lymphomas as seen at the Kenyatta National Hospital
in the 1990s.
DESIGN: Retrospective study of patients with non-Hodgkin's Iymphoma.
SETTING: Kenyatta National Hospital, Nairobi, Kenya, between January 1990 and
January 2000 inclusive.
SUBJECTS: Patients aged 13 years and above, with non-Hodgkin's Iymphomas.
RESULTS: Case records were available for 207 patients, 146 males and 60 females,
with one having had gender not clarified. Fifty two per cent of the patients were
aged less than 40 years and 18.4% over 60 years. Forty one per cent were not
properly classified histologically, seventy patients out of 190 evaluable (36.8%)
had stages IVA and IVB disease at diagnosis. Twenty five out of 77(32.5%) tested
positive for HIV infection, none of them being of the indolent variety. Up to
57.1% of cases of Burkitt's lymphoma tested positive for HIV infection.
Cyclophosphamide, doxorubicin, vincristine and prednisone, (CHOP) chemotherapy
was given to 68.7% of the patients with complete remission rates of 55.6% for
those who got a minimum of six courses of chemotherapy. Only 15.3% of 105
patients evaluable were followed up for 36 months and above, the majority of
patients having been lost to follow-up. Poor performance status at diagnosis
correlated with shorter follow-up durations (p<0.05).
CONCLUSION: A good percentage of the patients were not comprehensively
characterized pathologically. Standard treatment was offered to the majority of
patients, and those who could afford to purchase the medicines stood good chance
of achieving complete remission. Poor performance status at diagnosis correlated
with shorter follow-up durations and early stage disease correlated with longer
follow-up durations. Overall, the outlook for NHLs treated at KNH in the 1990s
appears to have improved tremendously.

OBJECTIVE: To assess post-surgical management of patients with breast cancer at
the Kenyatta National Hospital.
DESIGN: Retrospective analysis of patients treated for breast carcinoma at
Kenyatta National Hospital between January 1989 and January 2000.
SETTING: Kenyatta National Hospital.
SUBJECTS: Three hundred and seventy-four patients who had surgery or biopsy for
breast cancer at the Kenyatta National Hospital.
INTERVENTION: Chemo-hormonal therapy and/or radiotherapy for adjuvant,
metastatic, or palliative purposes.
RESULTS: Twenty-two patients received adjuvant chemotherapy, and 21 patients
received chemotherapy for metastatic disease. Forty-six patients received
adjuvant radiotherapy and 53 had radiotherapy for palliative purposes. One
hundred and twenty-six patients were given tamoxifen for adjuvant and metastatic
purposes. The median duration of follow-up was 20 months.
CONCLUSION: Chemotherapy is grossly underutilized in the treatment of breast
cancer at the Kenyatta National Hospital, and radiotherapy is also underutilized.
Follow-up durations are dismal and if this is used as a surrogate measure for
survival then survival durations for breast cancer patients are also dismal at
the Kenyatta National Hospital.

OBJECTIVE: To determine the clinical and haematological factors associated with
treatment and outcome of chronic myeloid leukaemia (CML) at Kenyatta National
Hospital.
DESIGN: Retrospective survey of patients treated for chronic myeloid leukaemia.
SETTING: Kenyatta National hospital, Nairobi, Kenya, between April 1990 and
August 2000.
SUBJECTS: Patients with chronic myeloid leukaemia.
RESULTS: One hundred and four patients, 55 males and 49 females, age range 10-72
years with a median age of 35 years. Treatment with busulphan getting less
popular in favour of hydroxyurea. Median follow-up 20 months with none of the
clinical and haematological parameters impacting significantly on duration of
follow-up.
CONCLUSION: CML occurs at a younger age-group in Kenya, and none of the clinical
or haematological parameters appears to impact on follow-up duration

A 17 year old male patient with nodular sclerosis Hodgkin's disease had a relapse of lymphocyte depleted type ten years after entering complete remission with chemotherapy and radiotherapy. This is the first documented case in our experience of relapse after very long disease free interval. A review of the literature of late relapses in Hodgkin's disease is also presented. Relapses have been recorded from three years to twenty years, although few very late forms are registered. Long term follow up will be necessary to document the role of the different therapeutic regimen.

The process of carcinogenesis is complicated and in most cases requires several steps of cellular transformation resulting from various molecular signals brought about by interactions between carcinogens and the cellular genome. Cancers in which cellular transformation does not require numerous processes tend to occur in younger age groups while cancers of the advancing age tend to be those in which the process of cellular transformation occurs through complex molecular processes that require ample time for induction.

Recent studies have suggested that Epstein-Barr virus (EBV) may play a role in the etiology of Hodgkin's disease (HD). In a previous study, we used a latent membrane protein 1 (LMP1)-specific antibodies to examine archival material from 74 British children with HD and found 50% of cases to be positive. It is known that there are geographic and ethnic variations in the incidence of HD. We have investigated LMP1 status in formalin-fixed, paraffin wax-embedded lymph nodes with HD involvement from 53 children and 48 adults from Kenya using immunohistochemical staining. We also developed sensitive and specific in vitro gene amplification protocols for examining the EBV strain type in such material using several combinations of primers derived from the EBNA 2 and EBNA 3 coding regions. LMP1 positivity was present in 100% of the pediatric cases (two lymphocyte-predominant, 25 nodular sclerosis, 16 mixed cellularity, 5 lymphocyte depletion, and 5 unclassified) and in 66% of the adult cases (two of three lymphocyte-predominant, 26 of 39 nodular, sclerosis, two of two mixed cellularity, and two of four lymphocyte depletion). Tests to type the EBV strain were undertaken in 25 EBV-positive pediatric cases. A combination of type-specific polymerase chain reactions for EBNA 2 and EBNA 3C genes indicated that seven patients had type 1, eight had type 2, and 10 had dual infections with both types. Five cases with dual infections were further investigated using a sensitive in situ hybridization for the EBV-encoded, small nuclear nonpolyadenylated RNAs (EBERs). EBER transcripts were detected in Reed-Sternberg and Hodgkin cells and in occasional infiltrating lymphocytes. These observations indicate that in Kenya EBV is consistently associated with pediatric cases of HD, and that biopsies from a number of such cases appear to carry both type 1 and type 2 viral sequences.

Fifty five sickle cell anaemia (SCA) patients at the Kenyatta National Hospital were studied with a view to elucidating their cardiovascular status. Their age range was 13 to 27 years (median 18.9 years). They comprised 27 males and 28 females and their mean haemoglobin concentration was 8.5 +/- 1.4 g/dl. Haemoglobin level of 8.0-9.9 g/dl seen in 30 patients was noted to confer the lowest incidence of exertional dyspnoea and palpitation. Similarly, patients with this haemoglobin level had the lowest mean heart rate. The mean blood pressure was 114.9 +/- 9.9 mmHg systolic and 64.6 +/- 10 mmHg diastolic. Blood pressures, ejection fraction (EF) and differential fibre shortening (%D) were found to be directly related to haemoglobin level, whereas cardio-thoracic index (CTI) and left ventricular dimensions were inversely related to haemoglobin level. Mean echocardiographic measurements were within normal limits and left ventricular functions were found to be normal in 80.9% of the patients indicating that the majority of SCA patients at the Kenyatta National Hospital have good cardiac function