Imatinib (Glivec) and gastrointestinal stromal tumours in Nigerians.

BACKGROUND: To assess the response and the impact on the overall survival (OS) on c-KIT-positive (CD117+) gastrointestinal stromal tumours (GISTs) patients treated with imatinib mesylate. METHODS: Between July 2003 and December 2012, consenting patients with advanced c-kit-positive GISTs were enrolled to receive imatinib mesylate therapy at a dose of 400mg - 800mg daily, supplied gratis by Novartis Pharma (Basel, Switzerland) under its GIPAP initiative. Disease severity was based on tumour site, size and mitotic index at diagnosis. Clinical features together with drug toxicity, haematological and biochemical parameters were monitored. Overall survival (OS) reviewed at 12 months intervals over 5 years was computed using Kaplan-Meier RESULTS: There were 27 patients in all (17 males and 10 females with a median age of 52 years (range 26 - 83). Twenty three patients, 15 males and 8 females that have been followed up for at least 6 months were evaluated, aged 26-83 years (median = 56). There were 17 (73.9%) gastric tumours and 6 extragastric including 3 cases of peritoneum and 1 each of small gut, colon and rectum. At diagnosis, 21 (91.3%) cases were high risk, and 1 each fell into the intermediate and low risks, respectively. Ten patients (43.4%) including 5 with metastases presented with unresectable lesions. Five patients (21.7%) had complete tumour resection, 5 (3 with metastases) had partial resections and 3 others with non-bulky, nonmetastatic diseases underwent no surgery. Imatinib was used as the primary therapy for all patients, except the 5 patients that underwent complete tumour resection. Nine (39.1%) patients were lost to disease progression with a median survival of 16.7 +/- 10.7 (+/- SE) (95% CI = 0-37.6) months. The overall survival at 2 years for all patients was 71.9%, which dropped to 65.9% at 4 years. CONCLUSIONS: Although a small number of GISTs, imatinib induced an extended remission in patients with advanced disease, most of whom would have been dead within a few months of diagnosis.

KRAS and BRAF mutations in Nigerian colorectal cancers.

PURPOSE: Activation of the KRAS oncogene is implicated in colorectal carcinogenesis and mutations have been reported in 30-50% of cases. BRAF mutation, though less common, is also reported and importantly associated with shorter progression-free interval. This study aims to determine the KRAS and BRAF mutation statuses of Nigerian colorectal cancers (CRC). METHODS: Mutation analysis was carried out on archival paraffin-embedded blocks of CRC tissues. KRAS codons 12, 13 and 61 and BRAF V600E were assessed by pyrosequencing after DNA extraction from 200 cases at the Leeds Institute of Molecular Medicine, St. James's University Hospital, UK. Mutation rates and the spectra were determined. RESULTS: Pyrosequencing was successful in 112 of 200 cases. KRAS mutation in codons 12 and 13 was demonstrated in 23 of 112 cases (21%); none in codon 61. BRAF mutation in codon 600 was demonstrated in 4.5%. CONCLUSION: This study shows that 21% of Nigerian CRC patients carry a KRAS mutation; half the rate in Caucasians; and that BRAF mutation also occurs in Nigerian CRC cancers.

Upper gastrointestinal endoscopy findings in Nigerians: a review of 170 cases in Lagos.

BACKGROUND: The advent of flexible endoscopy has made it possible to visualise the mucosa of virtually the entire intestine. This service is yet to be widely available in Nigeria. Existing reports on indications and findings at endoscopies are sometimes conflicting, with some recent reports suggesting a changing pattern of gastrointestinal diseases. OBJECTIVE: The study set out to evaluate the indications, endoscopic findings and their frequencies as well as any adverse outcome from the endoscopic examinations. METHODOLOGY: This was a retrospective study in which we reviewed the endoscopy records of the first one hundred and seventy patients that underwent upper gastrointestinal endoscopy at the Lagos State University Teaching Hospital. The patients' bio data, indications and findings during endoscopic examinations as well as any adverse outcome were documented. Data obtained were analysed using SPSS version 11. RESULTS: The majority of the patients were in the middle to elderly age with a peak in the 5th decade. The commonest indications for upper gastrointestinal endoscopy were; Dyspepsia, upper gastrointestinal haemorrhage, previously diagnosed peptic ulcer unresponsive to treatment and retrosternal discomfort or pain. Endoscopic request for variceal screening were uncommon. The commonest endoscopic findings were; features of gastroesophageal reflux disease, followed by gastroduodenitis (non-ulcer mucosal lesions in stomach and duodenum) and peptic ulcer disease. In 14 patients the endoscopy examination revealed normal findings. CONCLUSION: The role of endoscopy in the diagnosis and management of gastrointestinal disorders cannot be overemphasised. It is hereby recommended that provision of endoscopic facilities and training of necessary personnel be encouraged by all relevant agencies so that the services can be accessible and affordable by all who require it in view of its importance in patient management.

Interferon alfa-2a (Roferon-A) in the management of chronic hepatitis B infection: results of an open prospective study in Nigerian patients.

The efficacy and safety of recombinant interferon alfa-2a (rIFN) was evaluated in 26 adult Nigerian patients with chronic hepatitis B infection. Male and female patients with serological evidence of HBV infection (HBsAg and/or HBeAg positive patients) and abnormal liver histology were monitored for six months to confirm chronicity. At the end of the six months screening period eligible patient were enrolled into the study and treated with rIFN 4.5 MIU given three times a week for 6 months. Efficacy was assessed primarily by loss of HBV-DNA and/or HBeAg from serum and secondarily by loss of HBsAg and normalization of the liver histology. Safety was assessed by monitoring the leukocyte and platelet count over the treatment period whilst tolerability was assessed by recording the occurrence of adverse events (adverse drug reaction and intercurrent illness). At the end of therapy the response rate with respect to loss of HBV-DNA was 67% and 100% for HBeAg (i.e. for the six patients who were HBeAg positive at baseline). There was loss of HBsAg in 22.2% of the patients. A significant reduction in inflammation and necrosis scores was found among the 10 patients who had both baseline and term biopsies. The frequency of occurrence of adverse events was 53.8% and the laboratory safety parameters were not significantly affected by therapy (p > 0.05). 19.2% of the enrolled patients were withdrawn from the study prematurely. These results demonstrate that rIFN is effective in the management of CHB infection even in Nigerians. The high success rate associated with HBcAg clearance is particularly noteworthy.

Prevalence of serological markers of chronic hepatitis B virus infection in diabetics in the Lagos University Teaching Hospital, Lagos.

Hepatitis B virus (HBV) infection, a major world health problem, is hyper endemic in South-East Asia and sub-Saharan Africa including Nigeria. Being a major cause of morbidity and mortality, prophylaxis using the highly efficacious hepatitis B vaccine is recommended for those at risk. The prevalence of serological markers of chronic HBV infection was determined in a population of 100 outpatient diabetics and 80 non-diabetic controls at the Medical Outpatient Department of the Lagos University Teaching Hospital Idi-Araba between January and July 1992. Twenty diabetic patients [20%] and 14 controls [17.5%] had serological markers (HbsAg and antiHBc) indicating ongoing chronic HBV infection. The difference between diabetics and non-diabetic controls was not statistically significant (P>.05). None of the HbsAg and antiHBc positive diabetics [45%] and 8 control patients [57%] were HbeAg positive. The presence of serological markers was not related to the duration, type of diabetic treatment and degree of diabetic control. Our findings suggest that diabetics in Lagos appear not to be more predisposed to chronic HBV infection than the rest of the population, and therefore would require no special antiHBV prophylaxis.

Chronic liver disease in Lagos: a clinicopathological study.

OBJECTIVE: To evaluate the clinical features and stage of chronic liver disease at presentation in Lagos. METHODS: Clinical features, hepatic functional reserve (Child-Pugh classification) and liver histopathology were evaluated in 74 patients with chronic liver disease (CLD). RESULTS: The average age of the patients was 44.1 +/- 14yr and most (57, 67% ) were male. Ascites, hepatomegaly and jaundice were noted in 66%, 51%, 47% respectively. Hepatocellular carcinoma, liver cirrhosis and chronic hepatitis were seen in 35, 29, and 10 patients respectively. Significant impairment of hepatic functional reserve was noted in most of the patients with liver cirrhosis (76% ) and carcinoma (68% ). Hepatitis B and C infections were identified in 58% and 12% of the patients respectively. CONCLUSION: The majority of clinically identified patients with CLD had severe impairment of hepatic function with underlying advanced liver cirrhosis or hepatocellular carcinoma at presentation. Viral hepatitis was associated with most CLD and thus is potentially preventable and treatable when detected early. Public enlightenment programmes on hepatitis, widespread implementation of HBV vaccination, and surveillance of individual at-risk are essential for the control of hepatitis infection and the early detection of compensated CLD.