Pathology and oncology in Africa: education and training for the future in cancer research– East African Regional Meeting

According to the World Health Organisation (WHO), deaths from non-communicable diseases (NCDs) will increase globally, with the largest increase being on the African continent. On our continent, projections have indicated that deaths from NCDs will exceed all combined communicable, maternal, perinatal and nutritional diseases as the most common causes of death by 2030. Hence, the importance of a functional and improved pathology system in the diagnosis of cancer cannot be debated.Recently, the African Organization for Research and Training in Cancer (AORTIC) organised its East African regional meeting in Mwanza, Tanzania on 25–26 June 2015, with the focus being ‘Pathology and oncology: Education and training for the future in cancer research’. The main themes of the workshop were around improving cancer care and the role of twinning in Eastern Africa, in particular the Mwanza cancer project, telepathology, e-health and biobanking. The outcomes of a 2 day strategic meeting were developing an efficient and effective plan to guide the improvement in pathology training and cancer research in Africa.     

Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone

Adenomatous tumors in the middle ear and temporal bone are rare but highly morbid because they are difficult to detect prior to the development of audiovestibular dysfunction. Complete resection is often disfiguring and difficult because of location and the late stage at diagnosis, so identification of molecular targets and effective therapies is needed. Here, we describe a new mouse model of aggressive papillary ear tumor that was serendipitously discovered during the generation of a mouse model for mutant EGFR-driven lung cancer. Although these mice did not develop lung tumors, 43% developed head tilt and circling behavior. Magnetic resonance imaging (MRI) scans showed bilateral ear tumors located in the tympanic cavity. These tumors expressed mutant EGFR as well as active downstream targets such as Akt, mTOR and ERK1/2. EGFR-directed therapies were highly effective in eradicating the tumors and correcting the vestibular defects, suggesting these tumors are addicted to EGFR. EGFR activation was also observed in human ear neoplasms, which provides clinical relevance for this mouse model and rationale to test EGFR-targeted therapies in these rare neoplasms.     

Surgical management of hepatocellular carcinoma after Fontan procedure

The Fontan operation has successfully prolonged the lives of patients born with single-ventricle physiology. A long-term consequence of post-Fontan elevation in systemic venous pressure and low cardiac output is chronic liver inflammation and cirrhosis, which lead to an increased risk of hepatocellular carcinoma (HCC). Surgical management of patients with post-Fontan physiology and HCC is challenging, as the requirement for adequate preload in order to sustain cardiac output conflicts with the low central venous pressure (CVP) that minimizes blood loss during hepatectomy. Consequently, liver resection is rarely performed, and most reports describe nonsurgical treatments for locoregional control of the tumors in these patients. Here, we present a multidisciplinary approach to a successful surgical resection of a HCC in a patient with Fontan physiology.     

Novel drug candidates for blast phase chronic myeloid leukemia from high-throughput drug sensitivity and resistance testing

Chronic myeloid leukemia in blast crisis (CML BC) remains a challenging disease to treat despite the introduction and advances in tyrosine kinase inhibitor (TKI) therapy. In this study we set out to identify novel candidate drugs for CML BC by using an unbiased high-throughput drug testing platform. We used three CML cell lines representing different types of CML blast phases (K562, EM-2 and MOLM-1) and primary leukemic cells from three CML BC patients. Profiling of drug responses was performed with a drug sensitivity and resistance testing platform comprising 295 anticancer agents. Overall, drug sensitivity scores and the drug response profiles of cell line and primary cell samples correlated well and were distinct from other types of leukemia samples. The cell lines were highly sensitive to TKIs and the clinically TKI-resistant patient samples were also resistant ex vivo. Comparison of cell line and patient sample data identified new candidate drugs for CML BC, such as vascular endothelial growth factor receptor and nicotinamide phosphoribosyltransferase inhibitors. Our results indicate that these drugs in particular warrant further evaluation by analyzing a larger set of primary patient samples. The results also pave way for designing rational combination therapies.     

Electric discharge patterns of ankle muscles during the normal gait cycle

EMG patterns in ankle muscles were examined during normal gait cycles in 147 healthy asymptomatic adults. In all subjects, the tibialis anterior (Ta) showed marked activities around the toe-off and before the heel-strike, and the gastrocnemius lateral head (Gl) showed marked activity during the midstance phase but no activity in the early part of the swing phase. The Ta activity contributed to ground clearance, prevention of foot-drop, and shock absorption at the heel-strike. The Gl activity contributed to push-off from the ground and prevention of foot-drop. The Ta activity consisted of double bursts with (15% of subjects) or without (44%) electric silence in the midswing phase, continuous discharge (33%), and triple discharge patterns (8%). The Gl activity consisted of a single-peak (95%) pattern or double-peak (5%) patterns.