Adult liver transplantation in Johannesburg, South Africa (2004 - 2016): Balancing good outcomes, constrained resources and limited donors.

BACKGROUND: Liver transplantation is the standard of care for the treatment of liver failure worldwide, yet millions of people living in sub-Saharan Africa remain without access to these services. South Africa (SA) has two liver transplant centres, one in Cape Town and the other in Johannesburg, where Wits Donald Gordon Medical Centre (WDGMC) started an adult liver transplant programme in 2004. OBJECTIVES:  To describe the outcomes of the adult liver transplant programme at WDGMC. METHODS:  This was a retrospective review of all adult orthotopic liver transplants performed at WDGMC from 16 August 2004 to 30 June 2016 with a minimum follow-up of 6 months. The primary outcome was recipient and graft survival and the effect of covariates on survival. Kaplan-Meier survival analysis included all adults who underwent their first transplant for end-stage liver disease (ESLD) (N=275). Proportional hazards regression analysis using hazard ratios (HRs) was conducted to determine which covariates were associated with a significantly increased risk of mortality. RESULTS:  A total of 297 deceased-donor liver transplants were performed during the study period; 19/297 (6.4%) were for acute liver failure (ALF) and the remainder were for ESLD. The median age of recipients was 51 years (interquartile range 41 - 59), and two-thirds were male. The most common cause of ESLD was primary sclerosing cholangitis. The median follow-up was 3.2 years, and recipient survival was characterised in the following intervals: 90 days = 87.6% (95% confidence interval (CI) 83.1 - 91.0), 1 year = 81.7% (95% CI 76.6 - 85.8), and 5 years = 71.0% (95% CI 64.5 - 76.5). Allograft survival was similar: 90 days = 85.8% (95% CI 81.1 - 89.4), 1 year = 81.0% (95% CI 75.8 - 85.2), and 5 years = 69.1% (95% CI 62.6 - 74.7). The most significant covariates that impacted on mortality were postoperative biliary leaks (HR 2.0 (95% CI 1.05 - 3.80)), recipient age >60 years at time of transplant (HR 2.06 (95% CI 1.06 - 3.99)), theatre time >8  hours (HR 3.13 (95% CI 1.79 - 5.48)), and hepatic artery thrombosis (HR 5.58 (95% CI 3.09 - 10.08)). The most common infectious cause of death was invasive fungal infection. CONCLUSIONS:  This study demonstrates that outcomes of the adult orthotopic liver transplant programme at WDGMC are comparable with international transplant centres. Management of biliary complications, early hepatic artery thrombosis and post-transplant infections needs to be improved. Access to liver transplantation services is still extremely limited, but can be improved by addressing the national shortage of deceased donors and establishing a national regulatory body for solid-organ transplantation in SA.

Use of the USDT flow immunosensor for quantitation of benzoylecgonine in urine.

The flow immunosensor works on a principle somewhat distinct from other immunoassay systems in that it performs a displacement immunoassay. Antibody-coated matrices are saturated with fluorescently labeled benzoylecgonine (BE), which is released and measured in the presence of BE-containing urine and measured downstream from the matrix. The same antibody matrix can be used for many samples. A flow immunosensor instrument, built by US Drug Testing, Inc., has recently received "Premarket Notification' (510(K)) from the Food and Drug Administration (FDA) to screen urine for the presence of the cocaine metabolite BE. The performance of the flow immunosensor for screening BE in urine was validated by comparison with results of a blind study using the Syva EMIT, the Abbott TDx and gas chromatography-mass spectroscopy (GC-MS). Potentially interfering drugs were also spiked into urine and evaluated using the flow immunosensor. While the FDA approval is for determining whether the BE concentration is above or below the 300 micrograms/l cutoff recommended by the National Institute of Drug Abuse, we have also shown that the flow immunosensor can be adapted to produce quantitative determinations of the amount of BE in the urine samples. The reliability of the quantitation was confirmed by testing 100 urine samples containing unknown amounts of BE using the flow immunosensor. GC-MS and the Abbott TDx system. Comparison of quantitative data obtained using the immunosensor and GC-MS showed a 97% correlation, compared with a much lower value for data from the TDx and GC-MS.

Epithelioid psammomatous melanotic schwannoma with osseous metaplasia.

Psammomatous melanotic schwannoma is a very rare soft tissue neoplasm, which is clinically, biologically, and histologically distinct from conventional schwannoma. A significant proportion of patients may present with Carney's heritable complex of myxomas, spotty pigmentation, and endocrine overactivity. Typically, the lesion is composed of spindled and epithelioid cells displaying abundant intracytoplasmic melanin pigment, together with the formation of psammoma bodies. We report an epithelioid example of this tumor arising in the anterior abdominal wall of a 23-year-old man. A unique feature was a peripheral rim of osseous metaplasia. The tumor was erroneously diagnosed as a metastatic malignant melanoma on initial examination owing to its immunohistochemical coexpression of S100 protein and HMB-45. Psammoma bodies have not to our knowledge been described in melanomas, and their presence serves as a useful clue to the diagnosis of psammomatous melanotic schwannoma.

Clinicopathological trends in colorectal carcinoma in a Black South African population.

The clinico pathological characteristics of colorectal carcinoma in 127 Black South African patients were studied. The main presenting symptoms were altered bowel habits in 70% of the patients, weight loss in 64.3% and abdominal pain in 47.1%. Anaemia was present in 75.7%. There was a 31% incidence of mucinous carcinoma with a particular predilection for the younger age groups. Mucinous tumors were found more commonly in Duke stage C and D than in earlier stages. Tumors arising from a pre-existing adenoma constituted to 5.5% of the lot of patients with cancer colon.

Gastric mucormycosis.

A case of gastric mucormycosis proven on culture and histologic examination and successfully treated with resectional surgery and Amphotericin B is described.

Primary malignant melanoma of the oesophagus. Report of a case with flow cytometric DNA analysis.

Primary malignant melanoma is a very rare tumour of the oesophagus, and although this is the first case reported in a black patient in South Africa, the clinical, radiographic and histopathological features were characteristic of this malignancy. Primary oesophageal melanoma is a highly lethal tumour--fewer than 2% of patients are surviving 5 years after diagnosis. Flow cytometric DNA analysis of the resected specimen in this case revealed two populations of malignant cells, one of which had grossly abnormal DNA. Existence of two clones of malignant melanoma cells supports the observations that this tumour is biologically aggressive, radioresistant and almost always incurable.

Are carotid body tumours malignant?

Carotid body tumours (CBTs) are slow-growing, malignant neoplasms by virtue of their local spread by continuity and contiguity and metastatic spread by lymph and blood. This article reports the findings of a pathological study of the growth characteristics of CBTs.

Insulinoma in a black South African. A case report.

A 69-year-old black woman with an insulinoma presented with recurrent episodes of sweating and confusion culminating in two episodes of hypoglycaemic coma. The diagnosis was confirmed by finding an inappropriately elevated serum insulin level in the presence of hypoglycaemia after a fast of 14 hours. Computed tomography revealed a large tumour in the head of the pancreas. Removal of the tumour necessitated partial resection of the head and body of the pancreas, which in turn necessitated certain repair and drainage procedures. Postoperative complications, while not insignificant, were acceptable. At 1-year follow-up the patient is well.

Volvulus of the sigmoid colon at Baragwanath Hospital.

Fifty-six patients treated for sigmoid volvulus over a period of 5 years are reviewed. The purpose of this study is to evaluate our management policy and to compare it with other studies, particularly from other parts of Africa. The patients were evaluated by retrospective allocation into one of three treatment modalities. Patients with clinical evidence of ischaemia underwent a Hartmann's procedure. There was a 33% mortality rate in this group. In those patients who had sigmoidoscopic reduction, a second-stage sigmoidectomy and primary anastomosis were performed. The results in this group were excellent. In the group of patients with failed sigmoidoscopic resection the majority underwent a Hartmann's procedure with a mortality rate of 15%.

Chemically resolved scanning tunneling microscopy imaging of Al on p-type Al0.1Ga0.9As(001)-c(2x8)(2x4).

The ability to chemically differentiate individual subsurface Al and Ga atoms, when imaging the Al0.1Ga0.9As(001)-c(2x8)(2x4) surface with scanning tunneling microscopy (STM), has been observed for the first time. In filled-state STM images first layer As atoms bonded to second layer Al atoms appear brighter than those bonded to second layer Ga atoms. This effect is only observed experimentally with p-type Al0.1Ga0.9As grown on p-type GaAs substrates and has been computationally modeled with density functional theory (DFT) calculations. It is hypothesized that chemical specificity is not observed on n-type material because the extra surface charge given to first layer As atoms by second layer Al atoms adds negligibly to the filled-state density of the surface, thus preventing the visualization of chemical specificity with filled-state STM imaging. The ability to distinguish whether first layer As atoms are bonded to second layer Ga and/or Al atoms in STM images shows that small differences in bond ionicity affect the local electronic structure of the material.

Cutaneous cryptococcosis and Kaposi's sarcoma occurring in the same lesions in a patient with the acquired immunodeficiency syndrome.

A 34-year-old woman presented with a history of fever, malaise and skin lesions. A diagnosis of Kaposi's sarcoma and acquired immunodeficiency syndrome (AIDS) was established, and in addition, the skin lesion which was biopsied also demonstrated cryptococcal infection. Disseminated cryptococcosis was later confirmed and the disease ran a florid course. The co-existence of different diseases within the same lesion is a feature of human immunodeficiency virus (HIV) infection, this being the third documented case of simultaneous Kaposi's sarcoma and cutaneous cryptococcosis occurring at the same site in a patient with AIDS. The nature of this co-existence is discussed with reference to the pathogenesis of Kaposi's sarcoma.

Association between human papillomavirus and carcinoma of the oesophagus in South African blacks. A histochemical and immunohistochemical study.

Twenty specimens from patients who had undergone oesophagectomy for invasive squamous carcinoma of the oesophagus were examined for morphological evidence of human papillomavirus infection; it was found in 13 specimens. Nineteen specimens showed focal epithelial hyperplasia of the non-neoplastic mucosa. The material was also submitted to immunoperoxidase and modified Feulgen staining to detect viral antigen. Positive Feulgen staining was detected in the superficial layers of the squamous mucosa in 15 specimens, while immunoperoxidase was entirely negative. This demonstrates a possible association between human papillomavirus and oesophageal carcinoma and that the modified Feulgen method may be more sensitive than immunoperoxidase for the detection of viral antigen. Electron microscopy and molecular hybridisation would have to be used for confirmation.

Rhinocerebral mucormycosis in diabetic keto-acidosis. A case report.

A case of diabetic keto-acidosis complicated by rhinocerebral mucormycosis is described. Early diagnosis, control of the diabetes, aggressive surgical debridement, and systemic antifungal therapy resulted in a successful outcome.

The influence of bond flexibility and molecular size on the chemically selective bonding of In2O and Ga2O on GaAs(001)-c(2 x 8)/(2 x 4).

The surface structures formed upon deposition of In2O and Ga2O by molecular beam epitaxy onto the arsenic-rich GaAs(001)-c(2 x 8)/(2 x 4) surface have been studied using scanning tunneling microscopy and density functional theory. In2O initially bonds, with indium atoms bonding to second layer gallium atoms within the trough, and proceeds to insert into or between first layer arsenic dimer pairs. In contrast, Ga2O only inserts into or between arsenic dimer pairs due to chemical site constraints. The calculated energy needed to bend a Ga2O molecule approximately 70 degrees, so that it can fit into an arsenic dimer pair, is 0.6 eV less than that required for In2O. The greater flexibility of the Ga2O molecule causes its insertion site to be 0.77 eV more exothermic than the In2O insertion site. This result shows that although trends in the periodic table can be used to predict some surface reactions, small changes in atomic size can play a significant role in the chemistry of gas/surface reactions through the indirect effects of bond angle flexibility and bond length stiffness.

Association between human immunodeficiency virus type 1 infection and cancer in the black population of Johannesburg and Soweto, South Africa.

A case-control study of 913 black cancer patients (aged 15-50 years) was undertaken to measure the association between human immunodeficiency (HIV) infection and cancers believed to have an infective aetiology. Controls were patients with cancers believed not to be infective in origin. The prevalence of HIV in the controls of 7.3% (24 of 325) was similar to the background HIV seropositivity in this population. Odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age, year of diagnosis, marital status and sex were calculated. There was a strong association between HIV infection and Kaposi's sarcoma (KS), with 27 of 33 cases being HIV seropositive, OR = 61.8 (95% CI 19.7-194.2) and an elevated association with non-Hodgkin's lymphoma (NHL), with 27 of 40 cases being HIV seropositive [OR = 4.8 (95% CI 1.5-14.8)]. The elevated odds ratio for KS associated with HIV infection accords with the observed increases in the incidence of KS in several sub-Saharan African countries where the prevalence of HIV is high. The odds ratio for NHL associated with HIV infection was lower than that reported in developed countries, and the reason for this is not clear. No other cancers, including cervical and liver cancers, showed significantly elevated odds ratios associated with HIV infection.