Paediatric kidney transplants from donors aged 1 year and under: an analysis of the Australian and New Zealand Dialysis and Transplant Registry from 1963 to 2018.

Kidneys from very small donors have the potential to significantly expand the donor pool. We describe the collective experience of transplantation using kidneys from donors aged ≤1 year in Australian and New Zealand. The ANZDATA registry was analysed on all deceased donor kidney transplants from donors aged ≤1 year. We compared recipient characteristics and outcomes between 1963-1999 and 2000-2018. From 1963 to 1999, 16 transplants were performed [9 (56%) adults, 7 (44%) children]. Death-censored graft survival was 50% and 43% at 1 and 5 years, respectively. Patient survival was 90% and 87% at 1 and 5 years, respectively. From 2000 to 2018, 26 transplants were performed [25 (96%) adults, 1 (4%) children]. Mean creatinine was 73 µmol/l ±49.1 at 5 years. Death-censored graft survival was 85% at 1 and 5 years. Patient survival was 100% at 1 and 5 years. Thrombosis was the cause of graft loss in 12% of recipients in the first era from 1963 to 1999, and 8% of recipients in the second era from 2000 to 2018. We advocate the judicious use of these small paediatric grafts from donors ≤1 year old. Optimal selection of donor and recipients may lead to greater acceptance and success of transplantation from very young donors.

A systematic review and meta-analysis of cold in situ perfusion and preservation of the hepatic allograft: Working toward a unified approach.

The efficacy of cold in situ perfusion and static storage of the liver is a possible determinant of transplantation outcomes. The aim of this study was to determine whether there is evidence to substantiate a preference for a particular perfusion route (aortic or dual) or perfusion/preservation solution in donation after brain death (DBD) liver transplantation. The Embase, MEDLINE, and Cochrane databases were used (1980-2017). Random effects modeling was used to estimate effects on transplantation outcomes based on (1) aortic or dual in situ perfusion and (2) the use of University of Wisconsin (UW), histidine tryptophan ketoglutarate (HTK), Celsior, and/or Institut Georges Lopez-1 (IGL-1) solutions for perfusion/preservation. A total of 22 articles were included (2294 liver transplants). The quality of evidence ranged from very low to moderate Grading of Recommendations, Assessment, Development and Evaluations score. Meta-analyses were conducted for 14 eligible studies. Although there was no difference in the primary nonfunction (PNF) rate, a higher peak alanine aminotransferase (ALT) was recorded in dual compared with aortic-only UW-perfused livers (standardized mean difference, 0.24; 95% confidence interval, 0.01-0.47); a back-table portal venous flush was undertaken in the majority of aortic-only perfused livers. There were no relevant differences in peak enzymes, PNF, thrombotic graft loss, biliary complications, or 1-year graft survival in comparisons between dual-perfused livers using UW, HTK, Celsior, or IGL-1. In conclusion, there is no significant evidence that aortic-only perfusion of the DBD liver compromises transplantation outcomes, and it may be favored because of its simplicity. However, there is currently insufficient evidence to advocate for the use of any particular perfusion/preservation fluid over the others. Liver Transplantation 23 1615-1627 2017 AASLD.

The Abdominal Reapproximation Anchor Device.

INTRODUCTION: Achieving primary fascial closure after damage control laparostomy can be challenging. A number of devices are in use, with none having yet emerged as best practice. In July 2013, at Westmead Hospital, we started using the abdominal reapproximation anchor (ABRA; Canica Design, Almonte, Ontario, Canada) device. We report on our experience. METHODS: A retrospective review of medical records for patients who had open abdomens managed with the ABRA device between July to December 2013 was done. Data extracted included age, sex, body mass index (BMI), reason for the open abdomen, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, number of laparostomies prior to ABRA placement, duration of placement, device complications, length of hospital and intensive care unit (ICU) stay, and outcomes. RESULTS: Four cases of open abdomens managed using the ABRA device were identified, with 3 a consequence of intra-abdominal sepsis and 1 a consequence of penetrating trauma. Mean BMI was 33.5 kg/m2, APACHE II score was 14.5, duration with open abdomen prior to ABRA placement was 11.75 days, duration with ABRA in situ was 9 days, duration of hospital stay was 64.25 days, and ICU stay was 37.75 days. Three patients (75%) achieved fascial closure, and 1 achieved skin closure. No incidences of enterocutaneous fistulae occurred. CONCLUSION: The ABRA is a unique emerging alternative to aid in achieving fascial closure in patients managed with open abdomens. Our case series demonstrates that it can be used effectively in selected patients. Studies are needed to compare its efficacy with more traditional methods.

A systematic review and meta-analysis of cold in situ perfusion and preservation for pancreas transplantation.

BACKGROUND: This study aimed to identify the most effective solution for in situ perfusion/preservation of the pancreas in donation after brain death donors, in addition to optimal in situ flush volume(s) and route(s) during pancreas procurement. METHODS: Embase, Medline and Cochrane databases were utilized (1980-2017). Articles comparing graft outcomes between two or more different perfusion/preservation fluids (University of Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK) and/or Celsior) were compared using random effects models where appropriate. RESULTS: Thirteen articles were included (939 transplants). Confidence in available evidence was low. A higher serum peak lipase (standardized mean difference 0.47, 95% CI 0.23-0.71, I2 = 0) was observed in pancreatic grafts perfused/preserved with HTK compared to UW, but there were no differences in one-month pancreas allograft survivals or early thrombotic graft loss rates. Similarly, there were no significant differences in the rates of graft pancreatitis, thrombosis and graft survival between UW and Celsior solutions, and between aortic-only and dual aorto-portal perfusion. CONCLUSION: UW cold perfusion may reduce peak serum lipase, but no quality evidence suggested UW cold perfusion improves graft survival and reduces thrombosis rates. Further research is needed to establish longer-term graft outcomes, the comparative efficacy of Celsior, and ideal perfusion volumes.

Renal transplantation: better fat than thin.

BACKGROUND: Obesity has been a relative contraindication for renal transplantation. This study evaluates the impact of pretransplant body mass index (BMI) on renal transplant outcomes in a single institution in the era of modern immunosuppression. MATERIALS AND METHODS: A 10-y retrospective analysis was undertaken of 454 consecutive patients who received a renal transplant at Westmead Hospital from January 1, 2001 to December 31, 2010. The role of pretransplant BMI on patient survival, graft survival, surgical complications, and postoperative complications was studied. RESULTS: The mean age of transplant of this study population was 45.4 ± 13.0 y. Live donation rate was 53.5%, and 60.6% were male. The median preoperative BMI was 25.6 (range, 14.3-51.4). One-year and 5-y patient survival were 97.4% and 86.6%, respectively, whereas 1-y and 5-y death-censored graft survival were 97.1% and 91.9%, respectively. Patients with BMI >30 did not exhibit any significant difference in survival or graft failure but had higher surgical wound infection rates (hazard ratio 3.95, P < 0.01). Patients with preoperative BMI <18.5 were associated with a six-fold increase in both death and death-censored graft failure (P < 0.01). CONCLUSIONS: Pretransplant obesity increases wound infection but is not a contraindication to renal transplantation. Future prospective studies are required to further define the impact of low preoperative BMI <18.5.

Significant elevations of serum lipase not caused by pancreatitis: a systematic review.

BACKGROUND: Many authors advocate lipase as the preferred serological test for the diagnosis of pancreatitis and a cut-off level of three or more times the upper limit of normal (ULN) is often quoted. The literature contains no systematic review that explores alternative causes of a lipase level over three times as high as the ULN. Such a review was therefore the objective of this study. METHODS: The EMBASE and MEDLINE databases (1985 to August 2013) were searched for all eligible articles. Predetermined data were extracted and independently analysed by two reviewers. RESULTS: In total, data from 58 studies were included in the final analysis. The following causes other than pancreatitis of lipase levels exceeding three times the ULN were found: reduced clearance of lipase caused by renal impairment or macrolipase formation; other hepatobiliary, gastroduodenal, intestinal and neoplastic causes; critical illness, including neurosurgical pathology; alternative pancreatic diagnoses, such as non-pathological pancreatic hyperenzymaemia, and miscellaneous causes such as diabetes, drugs and infections. CONCLUSIONS: A series of differential diagnoses for significant serum lipase elevations (i.e. exceeding three times the ULN) has been provided by this study. Clinicians should utilize this knowledge in the interpretation and management of patients who have lipase levels over three times as high as the ULN, remaining vigilant for an alternative diagnosis to pancreatitis. The medical officer should be aware of the possibility of incorrect diagnosis in the asymptomatic patient.

Use of pre-operative steroids in liver resection: a systematic review and meta-analysis.

BACKGROUND: By attenuating the systemic inflammatory response to major surgery, the pre-operative administration of steroids may reduce the incidence of complications. METHODS: A systematic review was conducted to identify randomized controlled trials (RCT) comparing pre-operative steroid administration with placebo during a liver resection. Meta-analyses were performed. RESULTS: Five RCTs were identified including a total of 379 patients. Pre-operative steroids were associated with statistically significant reductions in the levels of serum bilirubin and interleukin 6 (IL-6) on post-operative day one. There was a trend towards a lower incidence of post-operative complications and prothrombin time (PT), but this did not reach statistical significance. CONCLUSION: Pre-operative steroids may be associated with a clinically significant benefit in liver resection.

A systematic review of a liver-first approach in patients with colorectal cancer and synchronous colorectal liver metastases.

BACKGROUND: Since the liver metastases rather than the colorectal cancer itself is the main determinant of patient's survival, the 'Liver-First Approach (LFA)' with upfront chemotherapy followed by a hepatic resection of colorectal liver metastases (CLM) and finally a colorectal cancer resection was proposed. The aim of this review was to analyse the evidence for LFA in patients with colorectal cancer and synchronous CLM. METHODS: A literature search of databases (MEDLINE and EMBASE) to identify published studies of LFA in patients with colorectal cancer and synchronous CLM was undertaken focussing on the peri-operative regimens of LFA and survival outcomes. RESULTS: Three observational studies and one retrospective cohort study were included for review. A total of 121 patients with colorectal cancer and synchronous CLM were selected for LFA. Pre-operative chemotherapy was used in 99% of patients. One hundred and twelve of the initial 121 patients (93%) underwent a hepatic resection of CLM. In total, 60% had a major liver resection and the R0 resection rate was 93%. Post-operative morbidity and mortality after the hepatic resection were 20% and 1%, respectively. Ultimately, 89 of the initial 121 (74%) patients underwent a colorectal cancer resection. Post-operative morbidity and mortality after a colorectal resection were 50% and 6%, respectively. The median overall survival was 40 months (range 19-50) with a recurrence rate of 52%. CONCLUSIONS: Current evidence suggests that LFA is safe and feasible in selected patients with colorectal cancer and synchronous CLM. Future studies are required to further define patient selection criteria for LFA and the exact role of LFA in the management of synchronous CLM.

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.

Hypothermic machine perfusion in deceased donor kidney transplantation: a systematic review.

BACKGROUND: Hypothermic machine perfusion (HMP) of kidneys is intended to mitigate the deleterious effects of cold storage on organ quality, particularly when the cold ischemic time is prolonged or the donor is otherwise marginal. The use of HMP has remained controversial; however, a number of randomized controlled trials (RCTs) have recently been conducted to clarify its benefits. METHODS: We undertook a systematic search of the Medline and Embase databases and of the Cochrane Central Register of Controlled Trials. We included only RCTs in the meta-analysis. Outcomes analyzed were the incidence of delayed graft function (DGF), primary nonfunction (PNF), graft loss, and patient death at 1 y. RESULTS: We identified seven RCT trials and subjected them to meta-analysis, including 1353 kidney transplant recipients. Hypothermic machine perfusion significantly reduced the incidence of DGF (risk ratio [RR] 0.83, 95% confidence interval [CI] 0.72-0.96). There was no difference in the incidence of PNF (RR 0.78, 95% CI 0.36-1.68), graft loss at 1 y (RR 0.87, 95% CI 0.64-1.19), and patient death at 1 y (RR 0.91, 95% CI 0.60-1.37) between HMP and donor kidneys preserved using cold storage. CONCLUSIONS: There are few RCT comparing HMP and cold storage of kidneys in deceased donor kidney transplantation. Although these studies are small and heterogeneous in design, HMP appeared to be associated with a reduced incidence of DGF. No difference in the incidence of PNF, graft loss, or patient death at 1 y could be demonstrated.

Transarterial chemoembolization with irinotecan beads in the treatment of colorectal liver metastases: systematic review.

PURPOSE: For patients with unresectable colorectal liver metastasis (CRLM), transarterial embolization with the use of drug-eluting beads with irinotecan (DEBIRI) represents a novel alternative to systemic chemotherapy or local treatments alone. The present systematic review evaluates available data on the efficacy and safety of DEBIRI embolization. MATERIALS AND METHODS: A comprehensive search of medical literature identified studies describing the use of DEBIRI in the treatment of CRLM. Data describing adverse events, pharmacokinetics, tumor response, and overall survival were collected. RESULTS: Five observational studies and one randomized controlled trial (RCT) were reviewed. A total of 235 patients were included in the descriptive analysis of observational studies. Postembolization syndrome was the most common adverse event. Peak plasma levels of irinotecan were observed at 1-2 hours after administration. Wide variations in tumor response were observed. The median survival time ranged from 15.2 months to 25 months. In the RCT, treatment with DEBIRI was superior to systemic chemotherapy with 5-fluorouracil/leucovorin/irinotecan in terms of quality of life and progression-free survival. CONCLUSIONS: For patients with unresectable CRLM, particularly after failure to respond to first-line regimens, DEBIRI represents a novel alternative to systemic chemotherapy alone, transarterial embolization with other agents, or other local treatments (eg, microwave or radiofrequency ablation). In these reports, DEBIRI was safe and effective in the in the treatment of unresectable CRLM. Further RCTs comparing DEBIRI with alternative management strategies are required to define the optimal role for this treatment.

A systematic review of two-stage hepatectomy in patients with initially unresectable colorectal liver metastases.

OBJECTIVES: Selected patients with unresectable colorectal liver metastases (CLM) may be rendered resectable using the two-stage hepatectomy (TSH) approach. This review was conducted with the aim of collating and evaluating published evidence for TSH in patients with initially unresectable CLM. METHODS: Searches of the MEDLINE and EMBASE databases were undertaken to identify studies of TSH in patients with initially unresectable CLM. Studies were required to focus on the perioperative treatment regimen, operative strategy, morbidity, technical success and survival outcomes. RESULTS: Ten observational studies were reviewed. A total of 459 patients with initially unresectable CLM were selected for the first stage of TSH. Preoperative chemotherapy was used in 88% of patients and achieved partial and stable response rates of 59% and 39%, respectively. Postoperative morbidity and mortality after the first stage of TSH were 17% and 0.5%, respectively. Portal vein embolization (PVE) was used in 76% of patients. Ultimately, 352 of the initial 459 (77%) patients underwent the second stage of TSH. Major liver resection was undertaken in 84% of patients; the negative margin (R0) resection rate was 75%. Postoperative morbidity and mortality after the second stage of TSH were 40% and 3%, respectively. Median overall survival was 37 months (range: 24-44 months) in patients who completed both stages of TSH. In patients who did not complete both stages of TSH, median survival was 16 months (range: 10-29 months). The 3-year disease-free survival rate was 20% (range: 6-27%). CONCLUSIONS: Two-stage hepatectomy is safe and effective in selected patients with initially unresectable CLM. Further studies are required to better define patient selection criteria for TSH and the exact roles of PVE and preoperative and interval chemotherapy.

A systematic review of clinical response and survival outcomes of downsizing systemic chemotherapy and rescue liver surgery in patients with initially unresectable colorectal liver metastases.

BACKGROUND: Selected patients with unresectable colorectal liver metastases (CLM) may be rendered resectable after systemic chemotherapy. We reviewed the evidence of downsizing systemic chemotherapy followed by rescue liver surgery in patients with initially unresectable CLM. METHODS: Literature search of databases (Medline and PubMed) to identify published studies of neoadjuvant chemotherapy followed by liver resection in patients with initially unresectable CLM was undertaken and focused on response rate of chemotherapy and survival outcomes. RESULTS: Ten observational studies were reviewed. A total of 1,886 patients with initially unresectable CLM underwent systemic chemotherapy. An objective response was observed in 64% (range, 43-79%) of patients after systemic chemotherapy. Of these, 22.5% underwent macroscopically curative liver resection. Median overall survival was 45 (range, 36-60) months with 19% of patients alive and recurrence-free. CONCLUSIONS: Current evidence suggests that downsizing systematic chemotherapy followed by rescue liver resection is safe and effective for selected patients with initially unresectable CLM. Further studies are required to examine response rates and secondary resectability using new targeted molecular therapy-based regimens.

Portal triad clamping versus other methods of vascular control in liver resection: a systematic review and meta-analysis.

BACKGROUND: Portal triad clamping (PTC) is the most commonly used method of achieving vascular control during liver resection. However, the efficacy and safety of PTC, compared with those of other methods of vascular control, are uncertain. METHODS: A systematic review was conducted to identify randomized controlled trials (RCTs) comparing PTC with other methods of vascular control during liver resection. Endpoints included in-hospital mortality, need for transfusion, number of complications and length of hospital stay. Meta-analyses were performed using a random-effects model. RESULTS: Ten RCTs were identified; these included a total of 820 patients. No statistically significant differences between PTC and other forms of vascular control in liver resection were demonstrated. CONCLUSIONS: There is no evidence, on the basis of this meta-analysis of RCTs, of any difference between PTC and other forms of vascular control in liver resection.

Laparoscopic or open cholecystectomy in cirrhosis: a systematic review of outcomes and meta-analysis of randomized trials.

BACKGROUND: Cholecystectomy is associated with increased risks in patients with cirrhosis. The well-established advantages of laparoscopic surgery may be offset by the increased risk for complications relating particularly to portal hypertension and coagulopathy. METHODS: A systematic search was undertaken to identify studies comparing open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) in patients with cirrhosis. A meta-analysis was performed of the available randomized controlled trials (RCTs). RESULTS: Forty-four studies were analysed. These included a total of 2005 patients with cirrhosis who underwent laparoscopic (n= 1756) or open (n= 249) cholecystectomy, with mortality rates of 0.74% and 2.00%, respectively. A meta-analysis of three RCTs involving a total of 220 patients was conducted. There was a reduction in the overall incidences of postoperative complications and infectious complications and a shorter length of hospital stay in LC. However, frequencies of postoperative hepatic insufficiency did not differ significantly. CONCLUSIONS: There are few RCTs comparing OC and LC in patients with cirrhosis. These studies are small, heterogeneous in design and include almost exclusively patients with Child-Pugh class A and B disease. However, LC appears to be associated with shorter operative time, reduced complication rates and reduced length of hospital stay.

Systematic review of actual 10-year survival following resection for hepatocellular carcinoma.

BACKGROUND: Hepatic resection is a potentially curative therapy for hepatocellular carcinoma (HCC), but recurrence of disease is very common. Few studies have reported 10-year actual survival rates following hepatic resection; instead, most have used actuarial measures based on the Kaplan-Meier method. This systematic review aims to document 10-year actual survival rates and to identify factors significant in determining prognosis. METHODS: A comprehensive search was undertaken of MEDLINE and EMBASE. Only studies reporting the absolute number of patients alive at 10 years after first resection for HCC were included; these figures were used to calculate the actual 10-year survival rate. A qualitative review and analysis of the prognostic factors identified in the included studies were performed. RESULTS: Fourteen studies, all of which were retrospective case series, including data on 4197 patients with HCC were analysed. Ten years following resection, 303 of these patients were alive. The 10-year actual survival rate was 7.2%, whereas the actuarial survival quoted from the same studies was 26.8%. Positive prognostic factors included better hepatic function, a wider surgical margin and the absence of satellite lesions. CONCLUSIONS: The actual long-term survival rate after resection of HCC is significantly inferior to reported actuarial survival rates. The Kaplan-Meier method of actuarial survival analysis tends to overestimate survival outcomes as a result of censorship of data and subgroup analysis.

Endoscopic necrosectomy of pancreatic necrosis: a systematic review.

AIM: To review the current status of the novel technique of endoscopic necrosectomy in the management of pancreatic necrosis after acute pancreatitis. METHODS: Studies were identified by searching Medline, PubMed and Embase databases for articles from January 1990 to December 2009 using the keywords "acute pancreatitis", "pancreatic necrosis" and "endoscopy". Additional papers were identified by a manual search of the references from the key articles. Case series of fewer than five patients and case reports were excluded. RESULTS: Indications, techniques and outcomes of endoscopic necrosectomy were analysed. There were no randomised controlled trials identified. Ten case series were included in this analysis. There were a total of more than 1,100 endoscopic necrosectomy procedures in 260 patients with pancreatic necrosis. One hundred fifty-five were proven to be infected necrosis on culture. The overall mortality rate was 5%. The mean procedure-related morbidity rate was 27%. The rate of complete resolution of pancreatic necrosis with the endoscopic method alone was 76%. CONCLUSIONS: Endoscopic necrosectomy is a safe and effective treatment option in selected patients with pancreatic necrosis after acute pancreatitis. Future studies will be required to further define the selection criteria and the techniques for the endoscopic procedure.

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.