Kidney Transplantation Outcomes From Uncontrolled Donation After Circulatory Death: A Systematic Review and Meta-analysis.

BACKGROUND: Uncontrolled donation after circulatory death (uDCD) is a potential additional source of donor kidneys. This study reviewed uDCD kidney transplant outcomes to determine if these are comparable to controlled donation after circulatory death (cDCD). METHODS: MEDLINE, Cochrane, and Embase databases were searched. Data on demographic information and transplant outcomes were extracted from included studies. Meta-analyses were performed, and risk ratios (RR) were estimated to compare transplant outcomes from uDCD to cDCD. RESULTS: Nine cohort studies were included, from 2178 uDCD kidney transplants. There was a moderate degree of bias, as 4 studies did not account for potential confounding factors. The median incidence of primary nonfunction in uDCD was 12.3% versus 5.7% for cDCD (RR, 1.85; 95% confidence intervals, 1.06-3.23; P = 0.03, I 2 = 75). The median rate of delayed graft function was 65.1% for uDCD and 52.0% for cDCD. The median 1-y graft survival for uDCD was 82.7% compared with 87.5% for cDCD (RR, 1.43; 95% confidence intervals, 1.02-2.01; P = 0.04; I 2 = 71%). The median 5-y graft survival for uDCD and cDCD was 70% each. Notably, the use of normothermic regional perfusion improved primary nonfunction rates in uDCD grafts. CONCLUSIONS: Although uDCD outcomes may be inferior in the short-term, the long-term outcomes are comparable to cDCD.

Systematic Review of Preoperative Prognostic Biomarkers in Perihilar Cholangiocarcinoma.

Perihilar cholangiocarcinoma (pCCA) is an uncommon malignancy with generally poor prognosis. Surgery is the primary curative treatment; however, the perioperative mortality and morbidity rates are high, with a low 5-year survival rate. Use of preoperative prognostic biomarkers to predict survival outcomes after surgery for pCCA are not well-established currently. This systematic review aimed to identify and summarise preoperative biomarkers associated with survival in pCCA, thereby potentially improving treatment decision-making. The Embase, Medline, and Cochrane databases were searched, and a systematic review was performed using the PRISMA guidelines. English-language studies examining the association between serum and/or tissue-derived biomarkers in pCCA and overall and/or disease-free survival were included. Our systematic review identified 64 biomarkers across 48 relevant studies. Raised serum CA19-9, bilirubin, CEA, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and tumour MMP9, and low serum albumin were most associated with poorer survival; however, the cutoff values used widely varied. Several promising molecular markers with prognostic significance were also identified, including tumour HMGA2, MUC5AC/6, IDH1, PIWIL2, and DNA index. In conclusion, several biomarkers have been identified in serum and tumour specimens that prognosticate overall and disease-free survival after pCCA resection. These, however, require external validation in large cohort studies and/or in preoperatively obtained specimens, especially tissue biopsy, to recommend their use.

Evolution of laparoscopic pancreaticoduodenectomy at Westmead Hospital.

BACKGROUND: Despite its proposed benefits, laparoscopic pancreaticoduodenectomy (LPD) has not been widely adopted due to its technical complexity and steep learning curve. The aim of this study was to report a single surgeon's experience in the stepwise implementation of LPD and evolution of technique over a nine-year period in a moderate-high volume unit. METHODS: Carefully selected patients underwent LPD initially by hybrid approach (laparoscopic resection and open reconstruction), which evolved into a total LPD (laparoscopic resection and reconstruction). Data was prospectively collected to include patient characteristics, intraoperative data, evolution of technique and postoperative outcomes. RESULTS: A total of 25 patients underwent hybrid LPD (HLPD) and 20 patients underwent total LPD (TLPD). There was no 90-day mortality. Three patients developed a postoperative pancreatic fistula (POPF), all of which occurred in patients undergoing HLPD. There was no POPF in 20 consecutive TLPD. There was no evidence of anastomotic strictures in the hepaticojejunostomy in patients undergoing TLPD at long term follow up. CONCLUSION: A gradual and cautious progression from HLPD to TLPD is essential to ensure safe implementation into a unit. LPD should only be considered in carefully selected patients, with outcomes subjected to regular and rigorous independent audit.

Outcomes of endovascular, open surgical and autotransplantation techniques for renal artery aneurysm repair: a systematic review and meta-analysis.

BACKGROUND: Renal artery aneurysms (RAA) can be repaired with endovascular exclusion (EVR), open repair (OR), or ex-vivo repair with renal autotransplantation (ERAT). This systematic review compares repair indications, aneurysm characteristics, and complications following these interventions. METHODS: A systematic review of databases including MEDLINE, PUBMED, and EMBASE by two independent reviewers for studies from January 2000-November 2022. All studies evaluating repair indications, RAA morphology, morbidity and mortality following EVR, OR, and ERAT were included. RESULTS: A total of 38 studies were included with 1540 EVR, 2377 OR and 109 ERAT subjects. Increasing aneurysm size, or diameters >20 mm, were the most common repair indications across EVR and OR (n = 537; 48%), and ERAT (n = 23; 52%). All ERAT repairs were at or distal to renal artery bifurcations (n = 46). Meta-analyses demonstrated significantly shorter length of stay (LOS) with EVR compared to OR (mean difference -4.06, 95% confidence interval (CI) -5.69 to -2.43, P < 0.001). No significant differences were found in mean aneurysm diameter (P = 0.23), total complications (P = 0.17), and mortality (P = 0.85). Major complications (Clavien-Dindo ≥III) across studies most commonly included acute renal failure (EVR 4.9% vs. OR 7.0%). Nephrectomy was the most common major complication in ERAT (5.5%). CONCLUSIONS: Outcomes following EVR and OR of RAAs are comparable. EVR offers a shorter LOS, with no difference in morbidity or mortality. ERAT is currently only utilized for distal RAAs, however carries higher risk of infarction and nephrectomy necessitating specialized expertise or algorithms to assist appropriate selection of repair methods.

Outcomes of live renal donors with a history of nephrolithiasis; A systematic review.

The clinical outcomes of kidney donors with a prior history of nephrolithiasis are poorly defined. We conducted a systematic review assessing the post-donation clinical outcomes of kidney donors with a history of nephrolithiasis. Electronic databases (Ovid and Embase) were searched between 1960 and 2021 using key terms and Medical Subject Headings (MeSH) - nephrolithiasis, renal stones, renal transplantation and renal graft. Articles included conference proceedings and journal articles and were not excluded based on patient numbers. Primary outcome was donor stone-related event. Secondary outcomes were renal function upon follow-up or post-operative nephrectomy complications. In summary, 340 articles were identified through database search. We identified 14 studies (16 cohorts) comprising 432 live donors followed up for a median of 26 months post live kidney donation. Six donors donated the stone-free kidney whilst 23 live donors had bilateral stones. Mean stone size was 4.2 ± 1.4 mm (1-16) with average follow up duration of 21.1 months (1-149). Twelve studies provided primary outcome (n = 138 patients) and eight (n = 348) for secondary outcomes. One donor had a stone-related event upon follow up. A total of 195 patients had eGFR <60 upon follow up. However, they were not significantly different when compared to renal function of live donors that didn't have pre-donation nephrolithiasis. Many of the studies couldn't provide long term follow up, coupled with limited data regarding the nature of the pre-donation stone disease. In conclusion, this systematic review shows that we have very limited information upon which to base recommendation regarding pre-donation risk of post-donation complications. Longer term follow up is required and lifelong follow up with live donor registries will aid further understanding.

Utilizing the same incision for staged renal transplant in patients with polycystic kidney disease requiring hand-assisted laparoscopic nephrectomy.

BACKGROUNDS: Many autosomal dominant polycystic kidney disease (ADPKD) patients undergo nephrectomy and subsequent renal transplantation. We report our outcomes after hand-assisted laparoscopic nephrectomy (HALN) where a Rutherford-Morrison incision is used as a hand-port site and kidney extraction site, as well the future incision site for staged transplantation. METHODS: A retrospective review was performed on all adult nephrectomies for ADPKD by the Transplant Surgery department at Westmead Hospital between June 2011 and June 2021. Outcomes were compared between HALN, laparoscopic nephrectomy (LN) and open nephrectomy (ON) including operation time, hospital length of stay (LOS), post-operative complications, subsequent transplantation and post-transplantation wound complications. RESULTS: Twenty-two HALN, 8 LN and 5 ON were performed during the study period. Median kidney weights for HALN, LN and ON were significantly different (1575, 403, 3420 g respectively, P = 0.001). There was a significant difference in LOS between the HALN and ON (5.8 versus 9.8 days, P = 0.04), but not between HALN and LN (5.8 versus 5.1, P = 0.06). There was no significant difference for operation time (P = 0.34) and major complication rates (P = 0.58). There were 8 HALN, 5 LN and 2 ON who have had subsequent renal transplantation with one wound complication, an incisional hernia in the HALN group. CONCLUSION: Our HALN is associated with a shorter LOS and similar complication rate to ON and can be efficiently performed for significantly larger kidneys than LN without a significant difference in operation time or LOS. The same Rutherford-Morrison incision site can be used for transplantation.

Transplant Outcomes From Deceased Donors Dying With Burns Injury, a Systematic Review.

AIM: The ever-expanding organ supply and demand gap necessitates alternate sources of organ donors. Initially thought to be a contraindication, organ procurement from nonsurvivable burns patients is possibly an additional organ donor source. We aimed to conduct a systematic review investigating the prevalence and outcomes of the use of burn victims as a source of organ donation for transplantation. METHODS: Medline and EMBASE were searched between 1990 and 2020, using the following keywords: organ procurement, organ donation, organ transplantation, and burns. Studies were not excluded based on patient numbers and included both published abstracts/conference proceeding and journal articles. Studies were excluded if specific organs were not identified or if posttransplant outcomes were not recorded. Primary and secondary outcomes of interest were post-transplantation organ function and complications respectively. RESULTS: Six manuscripts met study inclusion criteria. Fourteen burns donors were identified, including both donation after circulatory death and donation after brain death pathways. The total body surface area of burn ranged from 4% to 90%. A total of 4 hearts, 2 lungs, 8 livers, 1 pancreas, and 24 kidneys were transplanted with varying duration of follow-up and outcomes. CONCLUSION: A very small number of studies have reported the posttransplant outcomes of organs derived from victims of burn injury, including very limited information regarding graft function in the short or long term. Hence, recommendations for the utilization of organs from victims of burn injury should remain guarded and subject to surveillance.

A First Case Report of Cytomegalovirus Infection Presenting With Perianal Fistula and Abscess Formation in a Kidney Transplant Recipient.

Cytomegalovirus infection after transplant has been dramatically reduced in the modern era with improved understanding of immunosuppression and perioperative transplant care. However, cytomegalovirus syndrome with or without tissue invasive disease can still lead to significant morbidity and mortality. Several organs can be involved: most commonly, the gastrointestinal tract, liver, pancreas, lung, and the transplanted renal allograft. Postoperative cytomegalovirus colitis after renal transplant is well recognized and described, with symptoms including abdominal pain, nausea, and diarrhea. Biochemistry can demonstrate pancytopenia with a leukopenia with or without histopathology confirmation. A high index of suspicion is required for a timely diagnosis. This is the first published case report of a patient with cytomegalovirus tissue invasion presenting with a perianal fistula and abscess formation.The diagnosis and management ofthis case with a literature review is discussed.

Using Probability Estimates to Evaluate a Patient With Weakness.

In this case report, we review how probabilistic reasoning can be implemented in retrospect to refine the diagnostic process. A 67-year-old female with a history of polymyalgia rheumatica (PMR) and a recent dental procedure presented with weakness, falls, and chills ongoing for two weeks. She reported pain in her shoulders and lower back. On presentation, she was febrile, and labs were notable for leukocytosis with neutrophilic predominance and an elevated erythrocyte sedimentation rate (ESR). Chest radiograph revealed a left lower lung opacity, which was not seen on a repeat film. She was treated with antibiotics for community-acquired pneumonia and steroids for an exacerbation of PMR. After eight days of hospitalization, she was transferred to a subacute rehabilitation facility. A month later, she was readmitted with worsening lower back pain and right lower extremity weakness. Imaging revealed discitis and osteomyelitis at L1-L2. A spinal epidural abscess was present, leading to severe compression of the cauda equina nerve roots. Aspirate was positive for group B streptococcus. With antibiotic treatment alone, she recovered with resolution of her weakness. In reviewing the literature, it becomes evident where improvements could have been made in the diagnostic process. Fever, leukocytosis, and neurological weakness are not commonly associated with PMR exacerbations. Lack of cough or shortness of breath, a persistently elevated erythrocyte sedimentation rate and C-reactive protein despite antibiotic treatment, and a repeat chest radiograph without an opacity suggest an alternative diagnosis to pneumonia. Persistent back pain with an insidious onset is a feature of untreated spinal epidural abscess. Steroid use and dental procedures are possible risk factors for spinal epidural abscess. By shedding light on how probabilities should be estimated, we hope to encourage probabilistic thinking to improve diagnostic accuracy. As with the best political forecasters, making precise probability estimates and frequently updating them may improve diagnostic accuracy for clinicians.

Aptamer-mediated doxorubicin delivery reduces HCC burden in 3D organoids model.

Epithelial cell adhesion molecule (EpCAM) is a surface marker which is frequently overexpressed in hepatocellular carcinoma (HCC) but minimally expressed on mature hepatocytes. We developed a specific aptamer against EpCAM (EpCAM-apt) and tested its potential as a drug delivery agent for HCC. The targeting ability of EpCAM-apt was confirmed in vitro and in vivo after which the complex was conjugated with doxorubicin (Dox) to form EpCAM-apt-Dox. The targeting efficacy of the drug-loaded complex against liver cancer stem-like cells (LCSCs) and therapeutic effects in HCC were evaluated. EpCAM-expressing (EpCAM+) HCC cells showed characteristics of stem like cells including greater proliferative capacity and tumour sphere formation. EpCAM-apt-Dox selectively delivered Dox to EpCAM+ HCC cells with high drug retention and accumulation versus control. EpCAM-apt-Dox reduced the self-renewal capacity and stem-like cell frequency in vitro. Elimination of cancer stem-like cells (CSCs) with EpCAM-apt-Dox significantly inhibited the growth of HCC cells and patient-derived HCC organoids but exerted minimal cytotoxicity to normal liver organoids. Moreover, EpCAM-apt-Dox suppressed the growth of xenograft tumours derived from HCC organoids in vivo and prolonged mouse survival without inducing adverse effects to major organs. Thus, aptamer-based drug delivery to the stem-like cell population is a promising strategy for HCC treatment.

Renal allograft compartment syndrome: a review.

Renal allograft compartment syndrome (RACS) is the result of extrinsic compression resulting in graft dysfunction and loss due to ischaemia. A literature review was performed by computerized searches from the following data sources Medline, EMBASE, PubMed and Cochrane Library databases. Risk factors include size mismatch between graft and recipient. Intraoperative suspicion should be exercised if there is poor tissue turgor, cyanosis and loss of urine output upon fascial closure. Doppler ultrasound is the modality of choice amongst the literature to aid in diagnosis of RACS. From our study, the accepted form of treatment is early detection and appropriate surgical intervention. Nevertheless, it is clear from the paucity of literature that further investigation into this area of transplantation is necessary.

A diagnostic and management conundrum in a rare case of a small renal mass UTUC with IVC and bilateral renal vein tumour thrombus.

Upper Tract Urothelial Carcinomas (UTUC) are generally uncommon, accounting for approximately 5% of all urinary tract tumours. This report describes a unique Case of a 52-year-old-male with no known risk factors or symptoms of UTUC, who presented with bilateral sub-massive pulmonary embolus (PE). Subsequent computed tomography (CT) demonstrated a small (<2cm) right cortical based mass a discordant venous tumour thrombus (VTT) extending in the IVC, up to the level of the hepatic vein and bilateral renal veins. The patient had surgical excision in the form of right radical nephroureterectomy, IVC resection with bovine pericardial graft reconstruction and left renal autotransplant.

How to repair a donor renal vein injury with an inferior vena cava patch.

Shortage of supply of organs for donation means that every viable organ should be given the best chance possible for transplantation. As such, we present a method of renal vein reconstruction of a deceased donor kidney following injury during the organ recovery process.

Expansion of dysfunctional CD56-CD16+ NK cells in chronic hepatitis B patients.

BACKGROUND & AIMS: Natural killer (NK) cells are primary innate effector cells that play an important role in the control of human viral infections. During chronic viral infection, NK cells undergo significant changes in phenotype, function and subset distribution, including the appearance of CD56-CD16+ (CD56-) NK cells, previously identified in chronic human immunodeficiency virus (HIV) and hepatitis C virus infection. However, the presence of CD56- NK cells in the pathogenesis of chronic hepatitis B (CHB) remains unknown. METHODS: Phenotype and function of CD56- NK cells from patients with CHB (n = 28) were assessed using flow cytometry and in vitro stimulation with HBV antigen. RESULTS: CHB patients had a higher frequency of CD56- NK cells compared to healthy controls in peripheral blood (6.2% vs 1.4%, P < .0001). Compared to CD56+ NK cells, CD56- NK cells had increased expression of inhibitory receptors, and reduced expression of activating receptors, as measured by MFI and qPCR. CD56- NK cells were less responsive to target cell and cytokine stimulation compared to their CD56+ counterparts. In addition, CD56- NK cells demonstrated defective dendritic cells (DCs) interactions resulting in reduced DCs maturation, lower expression of NK CD69 and impaired capacity of NK cells to eliminate immature DCs in co-culture studies. Finally, frequency of CD56- NK cells was positively correlated with serum HBV DNA levels. CONCLUSION: Chronic HBV infection induces the expansion of highly dysfunctional of CD56- NK cells that likely contribute to inefficient innate and adaptive antiviral immune response in chronic HBV infection.

Successful Expectant Management of Nonocclusive Thrombosis in Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation can be complicated by thrombosis in the early post-transplant period. METHODS: We performed a single-center retrospective study examining risk factors, management, and outcomes of modern era SPK transplants. We reviewed 235 recipients over 10 years (January 1, 2008, to September 1, 2017). We used multivariate analysis to examine donor, recipient, and operative risk factors for thrombosis. RESULTS: Forty-one patients (17%) had a thrombosis diagnosed on postoperative imaging, but 61% of these patients (n = 25/41) did not lose their graft secondary to the thrombosis. Nine patients (22%) were managed with watchful waiting and serial imaging, 12 (29%) were managed with therapeutic anticoagulation, and 4 (10%) required laparotomy and graft thrombectomy. Sixteen of 235 pancreas grafts (6.8%) required pancreatectomy, and 10 of these cases occurred in the first half of the study, before 2012. The risk of thrombosis leading to graft loss increased 11.2-fold in recipients with a body mass index (calculated as weight in kilograms divided by height in meters squared) > 25 compared with others (odds ratio, 11.2; 95% CI, 1.1-116.7; P = .043). CONCLUSIONS: The majority of SPK transplants (61%) complicated by thrombosis of the pancreatic graft were salvaged by use of imaging, anticoagulation, and in select cases, laparotomy and graft thrombectomy.

An aptamer-based drug delivery agent (CD133-apt-Dox) selectively and effectively kills liver cancer stem-like cells.

Liver cancer has no effective therapies, hence a poor survival. Cancer stem-like cells not only contribute to cancer initiation and progression, but also to drug resistance, cancer metastasis, and eventually treatment failure. Hence, any approaches that can effectively kill cancer stem-like cells hold a great potential for cancer treatment. CD133 is a robust marker for liver cancer stem-like cells. We developed a specific aptamer against CD133 (CD133-apt), and then loaded this aptamer with an anticancer drug doxorubicin (CD133-apt-Dox). The efficacy of CD133-apt-Dox in targeting liver cancer stem-like cells and its overall effect in treating liver cancer were investigated using multiple in vitro and in vivo studies including in patients-derived liver cancer organoids. We have observed that CD133-apt could preferably delivered doxorubicin to CD133-expressing cells with efficient drug accumulation and retention. CD133-apt-Dox impaired the self-renewal capacity of liver cancer stem-like cells and attenuated their stem-ness phenotypes in vitro or in vivo. CD133-apt-Dox significantly inhibited the growth of liver cancer cells and patients-derived organoids and reduced the growth of xenograft tumours in nude mice inhibited the growth of DEN-induced liver cancer in immunocompetent mice. Hence, aptamer-mediated targeting of CD133 is a highly promising approach for liver cancer therapy.

Day-only elective cholecystectomy: early experience and barriers to implementation in Australia.

BACKGROUND: Day-only laparoscopic cholecystectomy (DOLC) has been shown to be safe and feasible yet has not been widely implemented in Australia. This study explores the introduction of routine DOLC to Westmead Hospital, and highlights the barriers to its implementation. METHODS: Routine day-only cholecystectomy protocol was introduced at Westmead Hospital in 2014. A retrospective review of patients who underwent elective laparoscopic cholecystectomy during a 12-month period in 2014 was compared to a 12-month period in 2018, to examine the changes in practice after implementation of a unit protocol. Data were collected on patient demographics, admission category, outcomes and re-presentations. RESULTS: A total of 282 patients were included in the study, of these 169 were booked as day procedures, with 124 (73%) successfully discharged on the same day. There was a significant increase in the proportion of patients booked as day-only from 2014 to 2018 (48% versus 73%, P < 0.001). Day-only failure rates (unplanned overnight admissions), readmissions and complication rates were comparable between the two periods. The most common reason for unplanned overnight admissions were due to intraoperative findings (n = 28/45). CONCLUSION: Routine DOLC can be adopted in Australian hospitals without compromise to patient safety. Unplanned overnight admission is predominantly due to unexpected surgical pathology and can be reduced by protocols for the use of drains and planned outpatient endoscopic retrograde cholangiopancreatography. Unplanned outpatient review can be minimized by optimizing both intra- and post-operative pain management. Individual surgeon and anaesthetist preferences remain an obstacle to a standardized protocol in the Australian setting.