Living donor liver transplantation in South Africa: the donor experience.

BACKGROUND: Living donor liver transplantation (LDLT) plays a crucial role in liver transplant programmes, particularly in regions with a scarcity of deceased donor organs and especially for paediatric recipients. LDLT is a complex and demanding procedure which places a healthy living donor in harm's way. Donor safety is therefore the overriding concern. This study aimed to report our standardised approach to the evaluation, technical aspects and outcomes of LDLT donor hepatectomy at Wits Donald Gordon Medical Centre. METHOD: The study population consisted of all patients undergoing LDLT donor hepatectomy since the inception of the programme in March 2013 until 2018. Sixty five living donor hepatectomies were performed. Primary outcome measures included donor demographics, operative time, peak bilirubin, aspartate and alanine transaminase levels postoperatively, length of hospital stay and postoperative complications using the Clavien-Dindo classification. RESULTS: The majority of the donors were female, most were parents with mothers being the donor almost 85% of the time. The median operative time was 374 minutes with a downward trend over time as experience was gained. The median length of hospital stay was 7 days. There was no mortality and the complication rate was 30% with the majority being minor (Grade 1). CONCLUSION: Living donor liver transplant from adult-to-child has been successfully initiated in South Africa. Living donor hepatectomy can be safely performed with acceptable outcomes for the donor. Wait-list mortality however remains unacceptably high. Expansion of LDLT as well as real change in deceased donor policy is required to address this issue.

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.

Heterozygote to homozygote related living donor liver transplantation in maple syrup urine disease: a case report.

Liver transplantation is an accepted treatment modality in the management of MSUD. To our knowledge, ours is only the second successful case to date of a patient with MSUD receiving an allograft from an RLD who is a heterozygous carrier for the disease. In view of the worldwide shortage of available organs for transplantation, heterozygote to homozygote transplantation in the setting of MSUD may provide a viable alternative for those awaiting transplantation. We report on the case of a two-yr-old infant with MSUD, who received a left lateral segment (segments II and III) liver transplant from his mother, a heterozygote carrier of one of the three abnormal genes implicated in MSUD. Post-operative BCAA levels normalized in our patient and remained so on an unrestricted protein diet and during times of physiological stress. To date, this is only the second case of a successful RLD liver transplant in a child with MSUD. Preliminary results indicate that RLD liver transplants are at least equivalent to deceased donor liver transplants in the treatment of MSUD, although longer term follow-up is required. Heterozygote to homozygote RLD transplant in patients with MSUD presents a new pool of potential liver donors.

Kidney transplant outcomes following the introduction of hand-assisted laparoscopic living donor nephrectomy: a comparison of recipient groups.

BACKGROUND: Laparoscopic donor nephrectomy has become the procedure of choice for living donor kidney transplantation in many centres. We report on our experience with hand-assisted laparoscopic donor nephrectomy (HALDN). We concentrated on graft function and postoperative surgical complications in the recipient population, and compared outcomes to a similar recipient group who had received kidneys procured by open living-donor nephrectomy (OLDN). METHOD: Following the receipt of institutional approval, the files of all patients who received a kidney transplant between September 2008 and June 2011 were reviewed. One hundred patients with end-stage renal disease received kidney transplantations from living donors. OLDN was performed in 65 donors, and 35 underwent HALDN. Delayed graft function (DGF) and postoperative complications were recorded. RESULTS: Six adverse events were reported, during which five patients presented with DGF. One DGF was reported in the HALDN group, and four in the OLDN group. The morbidity in the HALDN group (1/35, 3%) was a graft rupture secondary to acute rejection which required exploration and transplant nephrectomy. Reoperation was required in five patients in the OLDN group (5/65, 8%). This amounted to overall morbidity of 6%, with no recipient mortalities. CONCLUSION: As previously documented, HALDN is safe for the donor, and not inferior to OLDN. In this study, it was associated with neither an increased incidence of DGF, nor a higher complication rate in the transplant recipient, when compared to the cohort that received a kidney harvested using the OLDN technique.

Paediatric liver transplantation in Johannesburg revisited: 59 transplants and challenges met.

BACKGROUND: A paediatric liver transplant programme was started at the Wits Donald Gordon Medical Centre, Johannesburg, South Africa (SA), in November 2005. We reported on the first 29 patients in 2012. Since then we have performed a further 30 transplants in 28 patients, having met the major challenge of donor shortage by introducing a living related donor programme and increasing the use of split liver grafts. OBJECTIVE: To review the Wits Donald Gordon Medical Centre paediatric liver transplant programme to date. We describe how the programme has evolved and specifically compare the outcomes of the first cohort with the most recent 28 patients. METHODS: Case notes of all paediatric liver transplants performed between 14 November 2005 and 30 June 2014 were retrospectively reviewed. Data were analysed for age and weight at transplantation, indication and type of graft. Morbidity and mortality were documented, specifically biliary and vascular complications. Comparison was made between Era 1 (November 2005 - October 2012) and Era 2 (November 2012 - June 2014). RESULTS: A total of 59 transplants were performed in 57 patients. Age at transplantation ranged from 9 months to 213 months (mean 82.39 months) and weight ranged from 5 kg to 62 kg (mean 21 kg). A total of 23 whole livers, 10 reduced-size grafts, 14 split liver grafts and 12 living donor liver transplants (LDLTs) were performed. Eight patients were referred with fulminant hepatic failure (FHF), all in Era 2. Of these, three patients were successfully transplanted. Of the 57 patients, 45 are alive and well with actuarial 1-year patient and graft survival of 85% and 84% and 5-year patient and graft survival of 78% and 74%, respectively. Sixteen (25.42%) biliary complications occurred in 15 of our 59 transplants. Seven patients developed significant vascular complications. Comparing Era 1 with Era 2, mean age at transplant decreased from 100.86 months to 64.73 months, mean weight from 25.2 kg to 16.9 kg, and type of graft utilised changed with a trend away from the use of whole livers and reduced-sized grafts to split livers and segment 2,3 LDLT grafts. CONCLUSION: Initially limited by a shortage of donor organs, we aggressively explored optimal utilisation, splitting liver grafts from deceased donors as often as possible and establishing an LDLT programme. This increased access to donor livers allowed us to include patients with FHF and to perform retransplantation in recipients with early graft failure. It remains to offer liver transplantation to the entire paediatric community in SA, in conjunction with the only other established paediatric liver transplant unit, at Red Cross War Memorial Children's Hospital in Cape Town.

Paediatric liver transplantation for children treated at public health facilities in South Africa: time for change.

Paediatric liver transplantation (PLT) is the only therapeutic option for many children with end-stage chronic liver disease or irreversible fulminant hepatic failure, and is routinely considered as a therapy by paediatric gastroenterologists and surgeons working in developed countries. In South Africa (SA), a PLT programme has been available at Red Cross War Memorial Children's Hospital in Cape Town since November 1991, and another has rapidly developed at the Wits Donald Gordon Medical Centre in Johannesburg over the past decade. However, for most children with progressive chronic liver disease who are reliant on the services provided at state facilities in SA, PLT is not an option because of a lack of resources in a mismanaged public health system. This article briefly outlines the services offered at Chris Hani Baragwanath Academic Hospital--which is typical of state facilities in SA--and proposes that resources be allocated to establish an innovative, nationally funded centre that would enable greater numbers of children access to a PLT programme.

Paediatric liver transplantation in Johannesburg: initial 29 cases and prospects for the future.

BACKGROUND: The Wits Donald Gordon Medical Centre paediatric liver transplant programme is the second such unit in sub-Saharan Africa. Initiated in November 2005, it forms part of the centre's solid organ transplant unit, comprising kidney, liver and simultaneous kidney-pancreas arms. Initially established in the private sector, we recently received government approval to expand our programme into the provincial sector and have performed transplants on several provincial-sector patients. Current challenges relate to the lack of appropriately trained paediatric sub-specialists, specifically critical care practitioners and hepatologists. METHODS: Subsequent to institutional approval, a retrospective chart analysis of all paediatric liver transplants performed at our facility to date was conducted. RESULTS: Defining children as those under 18 years of age, 29 patients have received a cadaveric liver transplant since 2005, using 16 whole livers, 10 reduced-size grafts, and 3 split segments; 13 were transplanted with biliary atresia, 3 hyperoxalurea, 3 autosomal recessive polycystic disease, 2 alpha-1 antitrypsin deficiency, and 2 idiopathic, with the remainder for a wide spectrum of other pathologies. Seven patients received combined liver-kidney transplants. There were 3 in-hospital mortalities. The remaining 26 patients are all long-term survivors. We describe 7 acute surgical morbidities in 6 patients, and 8 long-term surgical morbidities. One patient was subsequently re-transplanted in Cape Town. CONCLUSIONS: Despite a shortage of organs, we have overcome a steep learning curve, with results comparable with other early series. The current threat to the continued viability of our unit is the lack of appropriately trained paediatric hepatologists and intensivists.

Overcoming the learning curve in hand-assisted laparoscopic live donor nephrectomy - a study in the animal model.

The demand for kidneys in South Africa is staggering. Only 38% of the kidney transplants done in 2008 were from related living donors. Laparoscopic living donor nephrectomy has been shown to have the advantages of decreased postoperative pain, better cosmesis and a quicker return to work when compared with the open technique. With limited surgical expertise, a realistic model was needed to overcome the learning curve. Methods. A total of 21 nephrectomies were performed on 12 pigs. The transperitoneal hand-assisted laparoscopic technique was used. Results. The median operative time was 75 minutes and the median warm ischaemic time 88 seconds. Three cases were aborted owing to major vascular injuries. Discussion. The advent of laparoscopic techniques has been associated with an increase in morbidity and complications in donor and recipient during the initial learning curve. We found that with our porcine model, 21 nephrectomies were adequate in overcoming the learning curve. After 15 nephrectomies no complications were noted.

Hand-assisted laparoscopic live donor nephrectomy - initial experience.

INTRODUCTION: The advantages of minimally invasive live donor nephrectomy have been well documented, with no adverse effect on graft function. Minimal access nephrectomy has now become the standard of care in many units. We have adopted the hand-assisted laparoscopic live donor (HALLDN) technique, and present our initial experience with the first 24 cases. MATERIAL AND METHODS: HALLDNs were performed trans-peritoneally. Primary outcomes included total operative time, warm ischaemic time, time to discharge, and post-operative complications. Warm ischaemic time was measured from the time of clamping the renal artery to the time of perfusing the kidney on the back table. RESULTS: Mean total operative time was 143 minutes and mean warm ischaemic time was 188 seconds. A downward trend was displayed for operative times. Mean time to discharge was 60 hours. A right nephrectomy was performed in 2 cases. No surgical morbidity is reported. We describe 1 donor mortality. DISCUSSION: Our results compare favourably with those documented in the literature. Aberrant renal vascular anatomy had no adverse effect on operative or warm ischaemic times. HALLDN proved beneficial in patients with a high BMI. CONCLUSION: Surgical experience is vital when performing HALLDN. Overcoming the learning curve with an animal model is beneficial.

Living kidney donor transplants over a 16-year period in South Africa: a single center experience.

BACKGROUND: Kidney transplantation is the treatment of choice for end-stage renal disease (ESRD). The number of patients on the waiting list is increasing due to an imbalance between organ supply and demand. This has led to an increase in the number of living donor transplants in most parts of the world. The benefits to the recipients must, however, be weighed against the risks to the donors. Long-term follow-up of the donors is therefore imperative to ascertain the risks of living kidney donation. MATERIALS AND METHODS: We reviewed the records of 571 potential living kidney donors (PLDs) in Johannesburg hospital over a 16-year period between 1990 and 2005. RESULTS: There were 1030 kidney transplants during this period, with 800 cadaveric and 230 actual living donor (ALD) transplants. There were 571 PLDs; however, 341 (59.7%) withdrew or were withdrawn because of medical and non-medical reasons. Among the 230 ALDs, the mean age of the donors was 35.2 ± 8.3 years; 55% were females; 24% were Blacks. Eighty-five percent were related to the recipients while 15% were unrelated. Mean duration of follow-up was 8.6 ± 6.4 years. The pattern of post-donation follow-up was excellent in 29.7%, adequate in 34% and unacceptable/poor in 36.3%, based on the number of clinic visits post-donation. Hypertension was noted in 24% of the donors during long-term follow-up. Three of the donors also developed significant microalbuminuria. CONCLUSION: There is a need to encourage living kidney donation, especially amongst the Black populations, and to emphasize the value and significance of post-donation follow-up visits to all potential donors.

Living kidney donor transplants over a 16-year period in South Africa: a single center experience

BACKGROUND:Kidney transplantation is the treatment of choice for end-stage renal disease (ESRD). The number of patients on the waiting list is increasing due to an imbalance between organ supply and demand. This has led to an increase in the number of living donor transplants in most parts of the world. The benefits to the recipients must, however, be weighed against the risks to the donors. Long-term follow-up of the donors is therefore imperative to ascertain the risks of living kidney donation.MATERIALS AND METHODS:We reviewed the records of 571 potential living kidney donors (PLDs) in Johannesburg hospital over a 16-year period between 1990 and 2005.RESULTS:There were 1030 kidney transplants during this period, with 800 cadaveric and 230 actual living donor (ALD) transplants. There were 571 PLDs; however, 341 (59.7%) withdrew or were withdrawn because of medical and non-medical reasons. Among the 230 ALDs, the mean age of the donors was 35.2 ± 8.3 years; 55% were females; 24% were Blacks. Eighty-five percent were related to the recipients while 15% were unrelated. Mean duration of follow-up was 8.6 ± 6.4 years. The pattern of post-donation follow-up was excellent in 29.7%, adequate in 34% and unacceptable/poor in 36.3%, based on the number of clinic visits post-donation. Hypertension was noted in 24% of the donors during long-term follow-up. Three of the donors also developed significant microalbuminuria.CONCLUSION:There is a need to encourage living kidney donation, especially amongst the Black populations, and to emphasize the value and significance of post-donation follow-up visits to all potential donors

Osteology of Paedocypris, a miniature and highly developmentally truncated fish (Teleostei: Ostariophysi: Cyprinidae).

Species of the cyprinid genus Paedocypris are among the smallest and most developmentally truncated fishes and vertebrates. Our analysis of their skeletal structure reveals a puzzling combination of extreme developmental truncation and an increased morphological complexity in sexually dimorphic characters. The skeleton of Paedocypris is characterized by reduction and loss and resembles in many aspects that of a larval/early juvenile stage of its close relatives. We found 61 characters that have been affected by developmental truncation. A comparison with the skeletal development of a close relative, the zebrafish Danio rerio, demonstrates that the majority of the absent bones or skeletal structures in Paedocypris are those that appear late in the ossification trajectory of the zebrafish. Thus, their absence in Paedocypris seems to be due to the simple developmental truncation of terminal stages in the ossification sequence. Our study of the sexually dimorphic structures in Paedocypris demonstrates that predominantly the male exhibits the more complex state. In relation to the female, male Paedocypris uniquely possess a cleithrum with a pointed posterior process that covers the scapula laterally, and a more medially situated posterior flange that contacts the dorsal area of the coracoid; a massive and heavily ossified uppermost pectoral radial tightly bound to the scapula; thickened and enlarged three uppermost pectoral-fin rays; a large triangular, dorsolaterally directed process on the outer arm of the massive os suspensorium; and a enlarged and shovel-like anterodorsally directed basipterygium; and a hypertrophied first pelvic-fin ray with additional anterior flanges that support keratinized pads of skin. Female Paedocypris show only one structure that is better developed than in males: the first proximal-middle radial and the anteriormost fin ray of the dorsal fin are more massive and more heavily ossified. Although the function and biological role of these dimorphisms is still unknown, we hypothesize that they are related to a special reproductive behavior. Paedocypris is a prime example for the recent claim that miniaturization among cyprinids is associated with evolutionary novelty only in developmentally truncated miniatures and not in proportioned dwarfs. Paedocypris offers a strong challenge to Schindleria as the most extreme example of developmental truncation known among fishes. We highlight the difficulties that developmentally truncated taxa frequently pose to the resolution of their phylogenetic position and propose an approach to overcome this problem. Our phylogenetic comparison to determine the systematic position of Paedocypris among cyprinids reveals that it shares not only a number of unique absences, but also highly unusual progressive characters with Sundadanio and Danionella, two other Asian miniature cyprinids. We hypothesize that the three genera form a monophyletic group. We further found that Paedocypris and Danionella share a number of uniquely derived characters pointing to a sister group relationship of the two.

Proximal suture line support in open abdominal aortic aneurysm repair: a comparative study.

OBJECTIVES: The aim of this study was to determine whether the collar graft (standard dacron graft with a customized flexible collar attached to the proximal rim) decreased anastomotic bleeding and the overall clamp time. DESIGN: Prospective randomised single center study. METHODS: Between November 2003 and January 2006, 21 patients were treated with a collar graft and 19 with a standard dacron graft. Routine endoaneurysmorraphy was used. Only infra-renal aneurysms between 5.5cm and 6.5cm were included. Aneurysms were diagnosed by CT scans. The total number of bleeding points, the total clamp time, and the number of teflon felt pledgets, was determined. RESULTS: The total number of bleeding points; the number of aortic re-clamps and total clamp time (minutes) per patient were all significantly lower in the collar graft group (1.2 versus 2, p<0.04; 0.5 versus 2.0, p<0.001; 13.6 versus 20.1, p<0.003 respectively). The number of teflon felt pledgets and new sutures used was significantly lower in the collar graft group (p<0.001 and p<0.003 respectively). CONCLUSION: The collar graft resulted in fewer anastomotic bleeding points and a shorter clamp time.

The myth of dorsal ribs in gnathostome vertebrates.

Traditionally, two types of rib are distinguished in gnathostomes: dorsal (upper) and ventral (lower, pleural) ribs. They are defined according to their position in the connective tissue system of the body: dorsal ribs develop at the intersection of the serially arranged myosepta with the horizontal septum that separates epaxial from hypaxial musculature, whereas ventral ribs develop at the intersection of myosepta with the peritoneum and usually encircle the body cavity. Distribution of rib types among gnathostomes has traditionally been reported as follows: elasmobranchs have dorsal ribs; all Actinopterygii have only ventral ribs with the exception of polypterids, and two subgroups of teleosts, which supposedly also have dorsal ribs; within Sarcopterygii tetrapods have dorsal ribs, whereas dipnoans have ventral ribs. Here, we report the development of ribs in polypterids, a taxon playing a crucial role in discussions on rib homology. We demonstrate that putative dorsal ribs of polypterids have a unique ontogeny and represent an autapomorphy of this taxon. We discuss previous hypotheses of rib homology and offer a more plausible (i.e. more parsimonious) alternative to the conventional interpretation. We conclude that dorsal ribs do not exist and that ribs of gnathostomes are ventral ribs.

Renal allograft preservation: a comparison of University of Wisconsin solution and of hypothermic continuous pulsatile perfusion.

A study was performed to compare early allograft function in kidneys preserved with University of Wisconsin (UW) solution to kidneys preserved by hypothermic pulsatile perfusion. The study consisted of two sets of data. The first set was a donor-paired study (matched data) of 30 heart-beating, hemodynamically stable donors. After removal from the donor each cooled kidney was individually prepared for preservation. One kidney was flushed with +/- 500 ml of UW solution and stored in UW solution on slushed ice. The other kidney was continuously perfused with cooled (4-6 degrees C) cryoprecipitated plasma. The kidneys were transplanted into suitable recipients in a random sequence. Twelve donors were excluded from the study because one or both kidneys were transplanted into recipients who had previously been transplanted. The remaining 36 kidneys were implanted into two similar groups after a mean of 19 hours in the pulsatile perfusion group and 18 hours in the UW solution group. The second set of data consisted of all the kidneys preserved in UW solution (n = 62) at our institution and of 57 kidneys preserved by hypothermic continuous pulsatile perfusion during the same period (mixed data) and was used to evaluate the effect of prolonged preservation (longer than 24 hours) on delayed graft function. Both of these groups were also comparable. Acute tubular necrosis (ATN) was defined as the need for dialysis during the 1st week after transplantation, and delayed function as the delayed clearance of creatinine during the early post-operative phase.(ABSTRACT TRUNCATED AT 250 WORDS)

A review of carcinoma of the colon and rectum over a 3-year period at Hillbrow Hospital, Johannesburg.

Fifty-one patients with adenocarcinoma of the large bowel seen at Hillbrow Hospital over a 36-month period are reviewed. The mean age at diagnosis was 53 years. Advanced disease was present in at least 60%. Carcinoma of the rectum constituted 48% and colonic carcinoma 52%. Cancer and polyps of the large bowel in urban blacks are no longer a rarity in urban hospitals.

Spontaneous closure of a gastrocolic fistula. A case report.

A medically unit elderly man who had documented healing of a gastrocolic fistula with conservative measures only is described. Only 5 such cases have previously been reported. Closure without surgery is a rare event and, in this case, was most probably aided by withdrawal of non-steroidal anti-inflammatory agents.

Intrapericardial herniation. A report of 2 cases.

Traumatic intrapericardial rupture is an infrequent occurrence and often associated with other fatal injuries. Two cases of delayed presentations of central tendon defects and intrapericardial herniation after blunt trauma to the chest and abdomen are reported.