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.

Renal transplant recipient and deceased-donor risk profiles at Wits Donald Gordon Medical Centre, Johannesburg, South Africa: A 9-year review.

BACKGROUND: Renal transplantation is the gold-standard therapy for end-stage renal disease. Decision-making around the acceptance of deceased-donor organs is complex and time sensitive. Risk scoring systems for both donors and recipients attempt to simplify the allocation of renal grafts to the most appropriate recipient. OBJECTIVES: To investigate the role of these transplant risk scores in the South African (SA) setting. METHODS: A total of 188 adult deceased-donor organ referrals over the 9-year period 1 January 2013 - 31 December 2021 were included. The Kidney Donor Risk Index (KDRI) and the UK KDRI were calculated for each donor. Recipients who were allocated these grafts were characterised, and the Hennepin Transplant Risk Score and the Kidney Transplant Morbidity Index (KTMI) were calculated. RESULTS: The median (interquartile range) KDRI was 1.2 (0.9 - 1.6), confirming that low- to average-risk donors were being utilised. Similarly, the median UK KDRI was 0.9 (0.8 - 1.2). Both these scores performed poorly in predicting graft and patient survival, with a C-statistic of 0.5. Renal recipient risk scores also demonstrated low- to average-risk patients being transplanted, with a median Hennepin score of 2 - 4 points and a KTMI of 2 points. These recipient scores predict increased recipient mortality at high scores, albeit with low sensitivity, and were not significantly associated with graft survival. CONCLUSION: Deceased-donor and renal recipient risk scores commonly used internationally performed poorly in predicting graft survival in our cohort, and should be used with caution in the SA setting. A conservative approach to organ donor referral and utilisation as well as renal transplant recipient listing was noted.

Wits Transplant Unit Annual Report 2022: Adult and paediatric liver transplantation.

In 2022, the Wits Transplant Unit performed 57 liver transplants: 33/57 adult (58%) and 24/57 paediatric (42%) recipients. At the beginning of 2022, 28 candidates were on the adult waitlist. Forty-six candidates were added to the waitlist during the year. Sixty-five percent of waitlisted candidate were transplanted. Adult candidates remained on the waitlist for longer than previous years, with 52% of them waitlisted for less than one year before undergoing liver transplantation. There was a decrease in adult pretransplant mortality to 9% in 2021 from 25% in 2020. The most common aetiology in waitlist candidates was alcoholic steatohepatitis (ASH)/non-alcoholic steatohepatitis (NASH) (36%) and in recipients cholestatic (primary sclerosing cholangitis (PSC) and primary biliary sclerosis (PBC)) (40%). Most adult recipients received a deceased donor graft (79%). Unadjusted recipient one- and three-year survivals were 75% (95% confidence interval (CI) 65 - 83) and 74% (95% CI 65 - 81), respectively. In the paediatric population, the most common aetiologies for both pretransplant candidates and transplant recipients remained cholestatic disease and acute liver failure. There was a decrease in paediatric pretransplant mortality from 27% in 2017 to 6% in 2021. Unlike the adult cohort, most paediatric recipients received a living donor graft (79%). Unadjusted one-year and three-year survival rates were 85% (95% CI 75 - 92) and 68% (95% CI 56 - 77), respectively.

The paediatric liver transplant experience in Johannesburg, South Africa: A broad overview and update.

BACKGROUND: The Wits Transplant Unit performed its first paediatric liver transplant in 2005. Initial experiences from the unit were published in 2012 and 2014. Since then, significant progress has been made in capacity-building the unit, improving outcomes and enhancing service delivery. This paper presents a broad overview and update of the unit's 17-year experience.   Methods: We conducted a retrospective review of all paediatric liver transplants performed in Johannesburg from 1 January 2005 to 31 December 2021 with a minimum one-year follow-up. Data were accessed from the Wits Donald Gordon Medical Centre Paediatric Liver Transplant Research Database (University of the Witwatersrand Human Research Ethics approval: M190749). The following data were collected: donor and recipient sociodemographic and clinical characteristics, details of transplant procedures, donor grafts and recipient outcomes (post-operative complications, graft and recipient survival).   Results: A total of 270 transplants were performed during the review period. Two thirds of recipients (n=180, 67%) were younger than 5 years at time of transplant and half (n=135, 50%) received a living donor graft. The most common indication for liver transplant was biliary atresia, followed by acute liver failure. Unadjusted recipient survival was 80% (95% CI: 75-85%) at one year, and 68% (95% CI: 59-75%) at five years. Waiting list mortality decreased from 27.3% in 2017 to 5.9% in 2021. One hundred and fifty-four (57.0%) recipients experienced at least one type of intervention requiring surgical complication - the most common being biliary in nature (n = 91; 33.7%).   Conclusion: Over last seventeen years, a sustainable paediatric liver transplantation service has been established in Johannesburg. Living donor, split and ABO incompatible liver transplants have been incorporated in response to the severe organ shortage in South Africa. However, our outcomes can be improved. Additionally, a national transplant initiative to coordinate timeous referrals and expand access to liver transplantation for children with severe acute and chronic liver failure is advised.

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 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.

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.

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.

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.

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.

Experiences in the diagnosis of brucellosis in dairy cows.

The Milk Ring, Serum Agglutination, Biological, Mercaptoethanol and Rose Bengal Plate Tests were used in combination to diagnose brucellosis in cows in some herds supplying milk to Johannesburg. The work was done in conjunction with routine testing of bulk milk supplies for public health control. 4 769 cows in more than 76 herds were involved in the tests. Results confirm that no single test can demonstrate all infected cows in a herd and that repeated testing is necessary. In an infected herd in which Strain 19 adult vaccination has been used some negative and suspicious cows will have to be sacrificed in eradicating the disease.

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 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 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.

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.