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Homograft availability and durability remain big challenges. Increasing the post-mortem ischaemic harvesting time beyond 24 h increases the potential donor pool. Cryopreservation, routinely used to preserve homografts, damages the extracellular matrix (ECM), contributing to valve degeneration. Decellularization might preserve the ECM, promoting host-cell infiltration and contributing towards better clinical outcomes. This study compared the performance of cryopreserved versus decellularized pulmonary homografts in the right ventricle outflow tract (RVOT) of a juvenile ovine model. Homografts (n = 10) were harvested from juvenile sheep, subjected to 48 h post-mortem cold ischaemia, cryopreserved or decellularized and implanted in the RVOT of juvenile sheep for 180 days. Valve performance was monitored echocardiographically. Explanted leaflet and wall tissue evaluated histologically, on electron microscopical appearance, mechanical properties and calcium content. In both groups the annulus diameter increased. Cryopreserved homografts developed significant (¾) pulmonary regurgitation, with trivial regurgitation (¼) in the decellularized group. Macroscopically, explanted cryopreserved valve leaflets retracted and thickened while decellularized leaflets remained thin and pliable with good coaptation. Cryopreserved leaflets and walls demonstrated loss of interstitial cells with collapsed collagen, and decellularized scaffolds extensive, uniform ingrowth of host-cells with an intact collagen network. Calcific deposits were shown only in leaflets and walls of cryopreserved explants. Young fibroblasts, with vacuoles and rough endoplasmic reticulum in the cytoplasm, repopulated the leaflets and walls of decellularized scaffolds. Young's modulus of wall tissue in both groups increased significantly. Cryopreserved valves deteriorate over time due to loss of cellularity and calcification, while decellularized scaffolds demonstrated host-cell repopulation, structural maintenance, tissue remodelling and growth potential.

Homografts are routinely stored by cryopreservation; however, donor cells and remnants contribute to immunogenicity. Although decellularization strategies can address immunogenicity, additional fixation might be required to maintain strength. This study investigated the effect of cryopreservation, decellularization, and decellularization with additional glutaraldhyde fixation on the strength and structure of ovine pulmonary homografts harvested 48 h post-mortem. Cells and cellular remnants were present for the cryopreserved group, while the decellularized groups were acellular. The decellularized group had large interfibrillar spaces in the extracellular matrix with uniform collagen distribution, while the additional fixation led to the collagen network becoming dense and compacted. The collagen of the cryopreserved group was collapsed and appeared disrupted and fractured. There were no significant differences in strength and elasticity between the groups. Compared to cryopreservation, decellularization without fixation can be considered an alternative processing technique to maintain a well-organized collagen matrix and tissue strength of homografts.

Adult giraffes reach heights of 4.5 meters with a heart-to-head distance of over 2 meters, making cranial blood supply challenging. Duplex ultrasound confirmed that the giraffe jugular vein collapses during head movement from ground level to fully erect, negating the possibility of a siphon mechanism in the neck. We showed that in a collapsible tube, flow is significantly influenced by a short length siphon structure over a simulated head to heart distance for a giraffe, with the length of the siphon structure determined according to brain case measurements.

Human papillomaviruses (HPVs) have been associated with a subset of head and neck squamous cell carcinomas (HNSCCs). The aim of this study was to determine the prevalence of HPV DNA in archived formalin-fixed paraffin-embedded tissue from patients with histologically confirmed HNSCCs in a South African cohort. A nested PCR was used for the detection of HPV DNA targeting the L1 gene. Positive samples were confirmed using an in-house hemi-nested PCR targeting the E6 gene and genotyped by sequence determination of amplicons. HPV DNA was detected in 57/780 (7.3%) samples, with the highest prevalence being in the sinonasal tract (16.0%) and oropharynx (10.8%). HPV16 was the most frequently detected type, being found in 26/57 (45.6%) positive samples. The prevalence of HPV DNA in HNSCCs found in this study was lower than that found in developed countries.

BACKGROUND Human herpesvirus-8 (HHV8) is a lymphotropic virus associated with different lymphoproliferative disorders, including primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD), diffuse large B-cell lymphomas, not otherwise specified, and the rare entity known as germinotropic lymphoproliferative disorder (GLPD). In PELs and GLPD the neoplastic cells also contain Epstein-Barr virus (EBV). In addition, occasional cases with atypical and overlapping features among these entities have been recognised, suggesting that the spectrum of the HHV8-related lesions may not be fully characterised. AIMS Here, we report two cases of lymphoproliferative disorder associated with HHV8 and EBV that further expand the spectrum of HHV8/EBV-positive lymphoproliferative disease. METHODS AND RESULTS Case 1 represented HHV8/EBV-positive extracavitary nodal PEL followed by pleural PEL. The striking characteristic of this case was the almost focal and intrasinusoidal localisation of the neoplastic cells and the association with Castleman's disease features. In the second case, we found the entire spectrum of HHV8-related disorders, i.e. MCD, GLPD, and PEL, coexisting in the same lymph node, underlining the variability, possible overlap and evolution among these entities. Both cases were well analysed with immunohistochemistry, determination of the EBV latency programme, and molecular analysis for clonality of immnoglobulin genes. In both patients, the disease followed an unexpected indolent course, both being still alive after 8 and 12 months, respectively. CONCLUSION Our findings represent further evidence of the overlap among HHV8/EBV-positive lymphoproliferative disorders, and underline a grey zone that requires further study; they further confirm the experimental evidence that lytic EBV replication influences HHV8-related tumorigenesis.

The skink Mochlus sundevallii is widespread throughout the African continent, but no detailed research on its ecology, reproduction and sexual dimorphism patterns has been performed yet. Here we address phenotypic and ecological data of M. sundevallii from the southernmost part of its distribution, using multiple populations from Southern Africa (mostly from South Africa) collected throughout different seasons. We aimed to assess the degree of intersexual and seasonal differences in morphological and reproductive aspects, as well as their experienced predation pressure. Morphological analyses confirmed that the species exhibits sexual dimorphism, evidenced by a larger body size for females and larger heads and longer limbs for males. However, tail autotomy (used as an estimation of predation rate) was found to be similar for both sexes and seasonally stable. Overall, the reproductive cycles of males and females were synchronised across the seasons, for an optimal breeding period during spring and summer, but males showed certain spermatogenic activity throughout the whole year.

Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe disease with fatalities. Awareness of potential sources of infection is important to reduce risk to healthcare workers and contacts. We detected CCHFV RNA in formalin-fixed, paraffin-embedded tissues from a spontaneous abortion that were submitted for histology 9 weeks after a suspected CCHFV infection in the mother.

We report a case of a malignant extra-adrenal paraganglioma with an underlying succinate dehydrogenase subunit B (SDHB) mutation in an African patient. The focus of this case is the lack of information regarding the underlying susceptibility genes in patients with paragangliomas and pheochromocytomas in Africa.

Background: We investigated the prevalence of HIV and human papilloma virus (HPV) infection in men with penile carcinoma.Method: This retrospective study investigated all men with penile carcinoma at the Universitas Academic Hospital in Bloemfontein, South Africa (January 2000–December 2008). Patients' age, HIV status, histological type of carcinoma and evidence of HPV infection were recorded. Statistical analyses included Student's t-test and Fisher's exact test where appropriate (2-tailed p-value < 0.05 indicated statistical significant).Results: Among 65 patients (mean age 50.9 years, range 37–69), the most common histological type was squamous cell carcinoma (80.0%). HIV status was known for 48 patients; 27 (56.2%) were HIV-positive. The mean age at presentation was 43.7 years (range 26–69) years in the HIV-positive and 57.2 years (range 26–89) years in the HIV-negative group. Approximately 55% of HIV-positive and 24% of HIV-negative patients showed histological evidence of HPV infection (p = 0.04). No significant difference was found with regard to histological type of carcinoma.Conclusion: Patients with penile carcinoma had a high prevalence of HIV infection. The HIV-positive group were significantly younger at presentation, with a higher prevalence of HPV infection, suggesting that HIV may contribute to HPV-associated penile cancer at a younger age.Key words: penis; carcinoma; human immunodeficiency virus (HIV); human papilloma virus (HPV)

Background: Most tumours of the head and neck are attributable to smoking and alcohol use, but an increasing proportion of head and neck tumours are caused by human papillomaviruses (HPVs). The aim of this study was to use in house molecular assays to detect and genotype HPV in biopsies from patients with histologically confirmed head and neck squamous cell carcinomas. In addition, the results were compared with p16 immunohistochemistry staining, which has been described as a potential marker for HPV infection. Methods: Biopsies of squamous cell carcinomas of the oropharynx, nasopharynx, larynx and hypopharynx from 112 South African patients were screened using three PCR assays targeting the L1 and E6 regions of HPV and p16 immunohistochemical staining. Results and conclusion: HPV was identified in 7 (6.3%) tumours, while 22 (19.6%) had positive p16 immunohistochemical staining. There was concordance between the results obtained using the three PCR assays. There was substantial agreement between the results of molecular tests and p16 immunohistochemistry for hypopharyngeal carcinomas, but only fair agreement for laryngeal and oropharyngeal carcinomas. Keywords: Human papillomavirus, Oropharyngeal carcinoma, Laryngeal carcinoma, Hypopharyngeal carcinoma, Nasopharyngeal carcinoma

Background Oculocutaneous albinism (OCA) is a group of genetic disorders characterized by diminished pigmentation of the skin, hair and eyes. Individuals with OCA are at increased risk to develop sun-induced skin malignancies. The incidence of malignant melanoma in OCA individuals is, however, very low. The aim of this study was to document pigmented and melanocytic skin lesions occurring in patients with OCA. Methods A prospective study was performed. Sixteen patients with OCA presenting at the Oncology and Dermatology Departments at Universitas Academic Hospital Annex in Bloemfontein, South Africa, were included. Selected clinically pigmented and/or melanocytic lesions were biopsied and studied by light microscopy. Results Twenty-four punch biopsies were taken. Ten dendritic freckles and 10 melanocytic nevi were confirmed histologically. The nevi, which occurred in eight patients, were found on sun-protected skin. All the freckles occurred on sun-exposed skin. Twelve patients had current or previous skin malignancies. No melanomas were present in the study population. Other skin lesions ranged from solar keratoses to squamous cell carcinomas. Conclusion The majority of pigmented lesions were dendritic freckles that occurred on sun-exposed skin. None of the patients had a current or previous diagnosis of malignant melanoma.

Background: Research has shown that the number of non-medicolegal (non-forensic) autopsies performed has declined worldwide in recent years. The aim of this study was to confirm a perceived decrease in the number of autopsies requested at the Universitas Academic Hospital Complex in Bloemfontein, and to evaluate clinicians' opinions on the possible reasons for this decline.Methods: All medical autopsies performed in four-year intervals between 1990 and 2010 were included in the study. Questionnaires were distributed to registrars and consultants in the Departments of Internal Medicine and Surgery.Results: The number of autopsies requested decreased from 308 in 1990 to only 60 in 2010, while the proportion of foetuses sent for autopsy increased from 2.3% of all autopsy requests in 1990 to 55.0% in 2010. Diseases of the respiratory system were the main cause of death in 1990, 1994 and 1998, while congenital conditions were the main finding in 2002, 2006 and 2010. The four most common reasons cited f...

Plasmablastic lymphomas are high-grade lymphomas that usually occur in immune-suppressed patients. Occasionally, they can arise from an underlying haematolymphoid malignancy, termed ‘transformed plasmablastic lymphoma’. In this report, we describe a case of chronic lymphocytic leukaemia and plasmablastic lymphoma in an elderly HIV-negative patient.

Background: The aim of this study was to determine the outcome of a one-hour training session on the correct technique of fine-needle aspiration biopsy (FNAB) by assessing adequacy of FNAB specimens received from clinicians at an academic hospital.Method: Six clinicians were recruited and their FNABs assessed, six months prior to, and then again after, a one-hour training session in correct technique. Questionnaires were completed prior to the training session and after the subsequent six-month period, to determine the subjective assessment of the clinicians' perceived value of the training on their aspiration technique.Results: Five of the clinicians had never received training in FNAB technique. The adequacy of the aspirates for all six clinicians did not improve, although this was not statistically significant. They performed a median of 15.5 FNABs in the six months prior to training, and 13.5 FNABs in the six-month follow-up period. Five of the six clinicians subjectively perceived the quality...

Paraganglia are neuroendocrine organs that originate from the neural crest cells that are closely associated with the autonomic nervous system. 1 Paragangliomas and phaeochromocytomas are tumours that arise from these organs. Paragangliomas are extra-adrenal tumours that can be divided into sympathetic and parasympathetic, and are further categorised by site. 1 The term “phaeochromocytoma” is reserved for intra-adrenal tumours. The most common location of these extra-adrenal paragangliomas is the inferior para-aortic region (also known as the organ of Zuckerkandl). 1 Other extra-adrenal sites that have been described include the bladder, pelvis, prostate, ovaries and thorax. 1 According to McNicol, the estimated incidence of paragangliomas is 1:300 000. At least 30% of paragangliomas have a hereditary occurrence. Approximately 10% are syndromic. 1 We describe a case of extra-adrenal pelvic paraganglioma that caused hypertension in pregnancy.

Plasmablastic lymphoma is an aggressive non-Hodgkin lymphoma predominantly seen in adult patients. Only eight cases of plasmablastic lymphoma in children have been published to date. In this report, we present an additional two cases. The first patient was a 9-year-old girl presenting with a nasal mass, while the second was a 15-year-old girl with swelling of the right side of the face and proptosis. Both patients were HIV-positive.

The aim of this study was to compare the histology of nasopharyngeal masses of HIV positive and HIV negative patients and to determine the prevalence of malignancy in nasopharyngeal masses in HIV positive patients. The records of all patients who had nasopharyngeal biopsies performed at the Department of Otorhinolaryngology, Universitas Academic Hospital between January 2006 and December 2011, were reviewed and 151 patients were identified. The HIV status of 110 of these patients was known: 78 (70.9 %) were HIV positive and 32 (29.1 %) were HIV negative. The CD4 count was known in 63 (80.8 %) of the HIV positive patients with the median CD4 count being 275 cells/μl (14–712 cells/μl). Most nasopharyngeal masses in HIV positive patients were benign. Malignancies were significantly more common in the HIV negative group than in the HIV positive group, with six (7.7 %) of the nasopharyngeal masses in the HIV positive group being malignant, while eight (25 %) of those in the HIV negative group were malignant. Most nasopharyngeal masses in HIV positive patients are due to lymphoid hyperplasia. The presence of large cervical lymphadenopathy should alert one to the possibility of a malignancy rather than a benign disease process.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract. Pathogenesis is linked to activating mutations identified in two proto-oncogenes, v-kit Hardy/Zuckerman 4 feline sarcoma viral oncogene homologue KIT (KIT) and the platelet-derived growth factor α (PDGFRα). In addition, these mutations affect response to treatment with tyrosine kinase inhibitors. In the present study, we report on the molecular characterisation of GISTs in the South African population. Tumour DNA was extracted from 46 GIST samples, followed by cycle sequencing of KIT exons 11, 13 and 17 and PDGFRα exons 12, 14 and 18. Fragment length analysis was used to detect a 6-bp duplication in KIT exon 9. Wild-type duplications were analysed further by PCR and sequencing of additional KIT and PDGFRα exons was performed. Overall, 78.3% of the samples had a mutation in KIT or PDGFRα. Of these, mutations were detected in KIT exon 11 (88.9%), PDGFRα exon 18 (8.3%) and KIT exon 9 (2.8%). Mutations varied from simple substitutions and duplications to large deletions (some with nucleotide insertions) resulting in missense mutations. In addition, seven single nucleotide polymorphisms were detected in 17 patients, one of which appears novel. The incidence of mutations in KIT exon 11 and PDGFRα exon 18 is consistent with the literature, however, the low incidence of KIT exon 9 mutations detected was unexpected. In contrast to previous western and Asian studies, this mutation appears to be rare in the South African population. The present study contributes to the molecular understanding of GISTs in the South African population.

Oculocutaneous albinism (OCA) is a group of genetic disorders characterized by diminished pigmentation of the skin, hair and eyes. Individuals with OCA are at increased risk to develop sun-induced skin malignancies. The incidence of malignant melanoma in OCA individuals is, however, very low. The aim of this study was to document pigmented and melanocytic skin lesions occurring in patients with OCA.A prospective study was performed. Sixteen patients with OCA presenting at the Oncology and Dermatology Departments at Universitas Academic Hospital Annex in Bloemfontein, South Africa, were included. Selected clinically pigmented and/or melanocytic lesions were biopsied and studied by light microscopy.Twenty-four punch biopsies were taken. Ten dendritic freckles and 10 melanocytic nevi were confirmed histologically. The nevi, which occurred in eight patients, were found on sun-protected skin. All the freckles occurred on sun-exposed skin. Twelve patients had current or previous skin malignancies. No melanomas were present in the study population. Other skin lesions ranged from solar keratoses to squamous cell carcinomas.The majority of pigmented lesions were dendritic freckles that occurred on sun-exposed skin. None of the patients had a current or previous diagnosis of malignant melanoma.

Gastrointestinal Stromal Tumour (GIST) is a rare disease but the most common mesenchymal neoplasm of the gastrointestinal tract. It has an incidence of 14.5-15 per million people. GIST tumor cells originate from the precursors of interstitial cells of Cajal (ICC), and are Kit/CD117 and CD34 positive. The key prognostic factors indicative of GIST metastasis, disease advancement and recurrence are the tumour size and the mitotic index. The anatomical site may also be informative for risk stratification. Despite existing differences in GIST clinicopathology, 75-80% of these tumors have an oncogenic mutation in the KIT (v-kit Hardy-Zuckerman feline sarcoma viral oncogene homolog) or PDGFRa (platelet-derived growth factor receptor, alpha polypeptide) genes. These gain of function mutations have been linked to GIST pathogenesis. Indeed both genes, which map to chromosome 4q12, belong to the type III tyrosine kinase family and encode highly homologous transmembrane glycoproteins. Neurofibromatosis 1 (NF1) patients have an increased risk of developing GISTs, although they will rarely have any KIT or PDGFRa mutations. The treatment of GIST patients has drastically changed since the introduction of tyrosine kinase inhibitors (TKI), such as Imatinib mesylate, which targets KIT and PDGFRa.

Salivary gland anlage tumour, also known as congenital pleomorphic adenoma, is a rare salivary hamartoma that presents in the nasopharynx of neonates. It is important to distinguish this lesion from other causes of neonatal respiratory distress. Treatment usually involves simple excision, and recurrence is rare. No cases of malignant progression have been reported in the literature. We report an interesting case referred to our unit a day after birth with respiratory distress.