Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial.

BACKGROUND: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF. METHODS: BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488). FINDINGS: Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference -0·5%, 95% CI -1·8 to 0·9; p=0·48). INTERPRETATION: Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation. FUNDING: Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter.

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.

Can response to locoregional therapy help predict longterm survival after liver transplantation for hepatocellular carcinoma? A systematic review.

For a selected group of patients with hepatocellular carcinoma (HCC), liver transplantation (LT) represents the best chance of a cure. Organ shortages necessitate an efficient allocation of resources and careful prioritization on the transplantation waiting list. In this review, we aim to collate and evaluate the published evidence for using response to locoregional therapies (LRTs), measured by modified Response Evaluation Criteria in Solid Tumors (mRECIST), as a predictor of longterm survival after LT. Our aim was to assess whether response to LRTs before LT for HCC, as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria, can help predict recurrence-free and/or longterm survival outcomes. We searched MEDLINE, Embase, and the Cochrane database. We included randomized controlled trials (RCTs), cohort, case control, and case series studies. Poster and conference abstracts were included. Studies were required to use RECIST or mRECIST criteria when assessing tumor response and were limited to LT for HCC only. A total of 15 records were included in the final systematic review: 7 published manuscripts and 8 conference abstracts. No RCTs were identified. Several included articles were conference abstracts with limited data available. No RCTs were found, and no meta-analysis was undertaken. Several retrospective cohort studies were identified that demonstrated statistically significant differences in survival and recurrence between different RECIST criteria after LT. Liver Transplantation 23 375-385 2017 AASLD.

The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study.

The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead of relying on these factors, we used poor tumor differentiation and cancer-related symptoms to exclude patients likely to have advanced HCC with aggressive biology. We initially reported similar 5-year survival for patients whose tumors exceeded (M+ group) and were within (M group) the Milan criteria. Herein, we validate our original data with a new prospective cohort and report the long-term follow-up (10-years) using an intention-to-treat analysis. The previously published study (cohort 1) included 362 listed (294 transplanted) patients from January 1996 to August 2008. The validation cohort (cohort 2) includes 243 listed (105 M+ group, 76 beyond University of California San Francisco criteria; 210 transplanted) patients from September 2008 to December 2012. Median follow-up from listing was 59.7 (26.8-103) months. For the validation cohort 2, the actuarial survival from transplant for the M+ group was similar to that of the M group at 1 year, 3 years, and 5 years: 94%, 76%, and 69% versus 95%, 82%, and 78% (P = 0.3). For the combined cohorts 1 and 2, there were no significant differences in the 10-year actuarial survival from transplant between groups. On an intention-to-treat basis, the dropout rate was higher in the M+ group and the 5-year and 10-year survival rates from listing were decreased in the M+ group. An alpha-fetoprotein level >500 ng/mL predicted poorer outcomes for both the M and M+ groups. CONCLUSION: Tumor differentiation and cancer-related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha-fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077-2088).

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.

CT volumetry is superior to nuclear renography for prediction of residual kidney function in living donors.

Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R(2) =26.2%, right kidney R(2) =26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J-test: P=.02, Cox-Pesaran test: P=.01) and Mayo formulas (J-test: P=.004, Cox-Pesaran test: P<.001). These observations support the use of CT volumetry for estimation of split kidney function in healthy individuals with normal kidney function and morphology.

The significance of pre-operative coronary interventions on outcome after pancreas transplantation.

Pancreas transplant candidates are at very high risk of coronary vascular disease. We hypothesized that the requirement for pre-operative coronary intervention (PCI) may be associated with an adverse impact on short- and long-term outcomes. Retrospective analysis of 366 consecutive primary pancreas transplants was undertaken. Outcomes were compared between recipients who had undergone PCI (n = 48) and those who had not (n = 318). In 48% (23/48) of instances, the PCI was initiated by the transplant cardiology evaluation. The recipients undergoing PCI were older than those not undergoing PCI (47.6 yr vs. 41.9 yr, respectively, p < 0.0001). Although not statistically significant, there was a higher rate of post-operative major cardiovascular events (MCVE) in the PCI group (10.4%) compared with those not undergoing PCI (4.7%) (RR [95% CI]: 2.0 [0.90-4.5]; p = 0.17). In the long term, there were no differences in the rate of death with graft function (p = 0.77) or rejection (p = 0.17). There were no statistically significant differences between the groups with respect to patient (p = 0.54), kidney (p = 0.76), or pancreas (p = 0.63) graft survival. PCI is not a risk factor for short-term perioperative events, and long-term transplant outcomes are equivalent to patients not requiring PCI. PCI, by itself, should not be considered a contraindication for pancreas transplantation, but should raise awareness of perioperative risk.

Techniques of pancreas graft salvage/indications for allograft pancreatectomy.

PURPOSE OF REVIEW: Despite improvements in pancreas allograft outcome, graft complications remain a significant cause of morbidity and mortality. This review analyses the issues involved in the management of conditions that may require graft pancreatectomy, including the indications and techniques for graft salvage. RECENT FINDINGS: With early recognition of graft complications, liberal use of radiological interventions, improved infection control, access to critical care and innovative surgical techniques, graft salvage is now feasible in many circumstances where graft pancreatectomy would previously have been necessary. SUMMARY: The outcome of pancreas transplantation continues to improve with advances in the management of graft-threatening complications.

Biliary complications in pediatric liver transplantation: Incidence and management over a decade.

This study analyzed how features of a liver graft and the technique of biliary reconstruction interact to affect biliary complications in pediatric liver transplantation. A retrospective analysis was performed of data collected from 2001 to 2011 in a single high-volume North American pediatric transplant center. The study cohort comprised 173 pediatric recipients, 75 living donor (LD) and 98 deceased donor (DD) recipients. The median follow-up was 70 months. Twenty-nine (16.7%) patients suffered a biliary complication. The majority of leaks (9/12, 75.0%) and the majority of strictures (18/22, 81.8%) were anastomotic. There was no difference in the rate of biliary complications associated with DD (18.4%) and LD (14.7%) grafts (P = 0.55). Roux-en-Y (RY) reconstruction was associated with a significantly lower rate of biliary complications compared to duct-to-duct reconstruction (13.3% versus 28.2%, respectively; P = 0.048). RY anastomosis was the only significant factor protecting from biliary complications in our population (hazard ratio, 0.30; 95% confidence interval, 0.1-0.85). The leaks were managed primarily by relaparotomy (10/12, 83.3%), and the majority of strictures were managed by percutaneous biliary intervention (14/22, 63.6%). Patients suffering biliary complications had inferior graft survival (P = 0.04) at 1, 5, and 10 years compared to patients without biliary complications. Our analysis demonstrates a lower incidence of biliary complications with RY biliary reconstruction, and patients with biliary complications have decreased graft survival.

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.

Prospective evaluation of a closed-incision negative pressure wound therapy system in kidney transplantation and its association with wound complications.

Introduction: Wound complications can cause considerable morbidity in kidney transplantation. Closed-incision negative pressure wound therapy (ciNPWT) systems have been efficacious in reducing wound complications across surgical specialties. The aims of this study were to evaluate the use of ciNPWT, Prevena™, in kidney transplant recipients and to determine any association with wound complications. Material and methods: A single-center, prospective observational cohort study was performed in 2018. A total of 30 consecutive kidney transplant recipients deemed at high risk for wound complications received ciNPWT, and the results were compared to those of a historical cohort of subjects who received conventional dressings. Analysis for recipients with obesity and propensity score matching were performed. Results: In total, 127 subjects were included in the analysis. Of these, 30 received a ciNPWT dressing and were compared with 97 subjects from a non-study historical control group who had conventional dressing. The overall wound complication rate was 21.3% (27/127). There was no reduction in the rate of wound complications with ciNPWT when compared with conventional dressing [23.3% (7/30) and 20.6% (20/97), respectively, p = 0.75]. In the obese subset (BMI ≥30 kg/m2), there was no significant reduction in wound complications [31.1% (5/16) and 36.8% (7/19), respectively, p = 0.73]. Propensity score matching yielded 26 matched pairs with equivalent rates of wound complications (23.1%, 6/26). Conclusion: This is the first reported cohort study evaluating the use of ciNPWT in kidney transplantation. While ciNPWT is safe and well tolerated, it is not associated with a statistically significant reduction in wound complications when compared to conventional dressing. The findings from this study will be used to inform future studies associated with ciNPWT in kidney transplantation.

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.

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.