Kristopher P. Croome

Total laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: oncologic advantages over open approaches?

Objective:To directly compare the oncologic outcomes of TLPD and OPD in the setting of pancreatic ductal adenocarcinoma. Background:Total laparoscopic pancreaticoduodenectomy (TLPD) has been demonstrated to be feasible and may have several potential advantages over open pancreaticoduodenectomy (OPD), including lower blood loss and shorter hospital stay. Whether potential advantages could allow patients to recover in a timelier manner and pursue adjuvant treatment options remains to be answered. Methods:We reviewed data for all patients undergoing TLPD (N = 108) or OPD (N = 214) for pancreatic ductal adenocarcinoma at our institution between January 2008 and July 2013. Results:Neoadjuvant therapy, tumor size, node positivity, and margin-positive resection were not significantly different between the 2 groups. Median length of hospital stay was significantly longer in the OPD group (9 days; range, 5–73 days) than in the TLPD group (6 days; range, 4–118 days; P < 0.001). There was a significantly higher proportion of patients in the OPD group (12%) who had a delay of greater than 90 days or who did not receive adjuvant chemotherapy at all compared with that in the TLPD group (5%; P = 0.04). There was no significant difference in overall survival between the 2 groups (P = 0.22). A significantly longer progression-free survival was seen in the TLPD group than in the OPD group (P = 0.03). Conclusions:TLPD is not only feasible in the setting of pancreatic ductal adenocarcinoma but also has advantages such as shorter hospital stay and faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. This study also demonstrated a longer progression-free survival in patients undergoing TLPD than those undergoing OPD.

Can we improve the morbidity and mortality associated with the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure in the management of colorectal liver metastases

BACKGROUND Meticulous selection of patients who can undergo the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure safely will be paramount to minimize the associated morbidity and mortality. METHODS We collected data prospectively on 14 consecutive patients who underwent the ALPPS procedure for planned resection of colorectal liver metastases at London Health Sciences Centre, Canada, between April 2012 and November 2013. RESULTS The median relative increase of the standardized future liver remnant after the ALPPS procedure was 93 ± 28%. The standardized future liver remnant rate of volume increase was 35 ± 13 mL/day. Biopsies of the FLR were taken during stage 1 and 2. These biopsies showed a mean preregeneration Ki-67 index of 0% and a postregeneration index of 14 ± 3%. All 14 ALPPS patients completed the 2-stage hepatectomy. No complications occurred after ALPPS stage 1. After ALPPS stage 2, 5 patients had complications (36%), with 2 patients (14%) having a severe complication (Clavien-Dindo ≥ IIIB). Median follow-up was 9 months. Overall survival at the time of follow-up was 100%. Recurrence developed in 2 patients. One patient had recurrence in the liver and lungs 5 months after stage 2 and was offered more chemotherapy. The other patient developed recurrence in the liver remnant 9 months after stage 2 and underwent additional chemotherapy with a possible future resection of the recurrence. CONCLUSION Low morbidity and negligible mortality can be achieved with the ALPPS procedure, and the high rates published in previous reports can be improved with refinements in technique and patient selection. The ALPPS approach may be a valid option to enable resection in selected patients with colorectal liver metastases considered unresectable previously by standard techniques.

Is the liver kinetic growth rate in ALPPS unprecedented when compared with PVE and living donor liver transplant? A multicentre analysis

BACKGROUND The clinical perspective on hepatic growth is limited. The goal of the present study was to compare hepatic hypertrophy and the kinetic growth rate(KGR) in patients after the ALPPS (Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy) procedure, portal vein embolization (PVE) and living donor liver transplantation. METHODS Volumetry and KGR of the future liver remnant (FLR) were compared from (15) patients undergoing ALPPS, (53) patients undergoing PVE, (90) recipients of living donor liver grafts and (93) donors of living donor liver grafts. RESULTS The degree of hypertrophy was significantly greater after ALPPS (84.3 ± 7.8%) than after PVE (36.0 ± 27.2%) (P < 0.001). The KGR was also significantly greater for ALPPS [32.7 ± 13.6 cubic centimetres (cc)/day] (10.8 ± 4.5%/day) compared with PVE (4.4 ± 3.2 cc/day) (0.98 ± 0.75%/day) (P < 0.001). The FLR of living donor donors had the greatest degree of hypertrophy (107.5 ± 39.2%) and was greater than after ALPPS (P = 0.02), PVE (P < 0.001) and in living donor-recipient grafts (P < 0.001). KGR (cc/day) was greater in FLR of living donor donors compared with both ALPPS (P < 0.001) and PVE (P < 0.001). The KGR in patients undergoing ALPPS and living donor liver transplantation had a linear relationship with the size of FLR. CONCLUSION FLR hypertrophy and KGR were greater after ALPPS than PVE. However, the degree of hypertrophy after ALPPS is not unprecedented, as KGR in the FLR from living donor donors is equal to or greater than after ALPPS. The KGR of the FLR in patients after ALPPS and living donor donors correlates directly with the size of the FLR.

Should a Lower Quality Organ Go to the Least Sick Patient? Model for End-Stage Liver Disease Score and Donor Risk Index as Predictors of Early Allograft Dysfunction

BACKGROUND There is a global tendency to justify transplanting extended criteria organs (ECD; Donor Risk Index [DRI] ≥ 1.7) into recipients with a lower Model for End-Stage Liver Disease (MELD) score and to transplant standard criteria organs (DRI < 1.7) into recipients with a higher MELD scores. There is a lack of evidence in the current literature to justify this assumption. METHODS A review of our prospectively entered database for donation after brain death (DBD) liver transplantation (n = 310) between January 1, 2006, and September 30, 2010, was performed. DRI was dichotomized as <1.7 and ≥ 1.7. Recipients were divided into 3 strata, those with high (≥ 27), moderate (15-26), and low MELD (<15) scores. The recently validated definition of early allograft dysfunction (EAD) was used. We analyzed EAD and its relation with donor DRI and recipient MELD scores. RESULTS The overall incidence of EAD was 24.5%. Mortality in the first 6 months in recipients with EAD was 20% compared with 3.4% for those without EAD (relative risk [RR], 5.56, 95% confidence interval [CI], 1.96-15.73; P < .001). Graft failure rate in the first 6 months in those with EAD was 27% compared with 5.8% for those without EAD (RR, 4.63; 95% CI, 2.02-10.6; P < .001). In patients with low MELD scores, a significantly increased rate of EAD (25%) was seen in patients transplanted with a high DRI liver compared with those transplanted with a low DRI liver (6.25%; P = .012). In moderate and high MELD recipients, there was no significant difference in the rate of EAD in patients transplanted with a high DRI liver (62%) compared with those transplanted with a low DRI liver (59%). CONCLUSION These results suggest that contrary to common belief it is not justified to preferentially allocate organs with higher DRI to recipients with lower MELD scores.

Is Liver Transplantation Appropriate for Patients with Potentially Resectable De Novo Hilar Cholangiocarcinoma

BACKGROUND Liver transplantation (LTX) is curative for selected patients with hilar cholangiocarcinoma (HC) in the setting of sclerosing cholangitis. However, the outcome of LTX vs liver resection (RTX) for patients with de novo HC remains unclear. STUDY DESIGN Patients with de novo HC treated by protocol LTX (n = 90) or RTX (n = 124) between 1993 and 2013 were reviewed. Based on preoperative imaging, RTX was pursued for Bismuth type III HC and LTX for unresectable Bismuth type IV. RESULTS Unadjusted analysis showed that overall survival after operation was greater for LTX than RTX (p = 0.003). One-, 3-, and 5-year overall survival rates, respectively, were 90%, 71%, and 59% for LTX and 81%, 53%, and 36% for RTX. Survival was not different between LTX and RTX after adjusting for patient age, lymph node metastases, and tumor size. After postoperative pathologic review, HC after RTX was reclassified as Bismuth-Corlette (B-C) IV, based on the necessity of multiple biliary anastomoses in 40 patients to more accurately compare treatment outcomes. Overall survival was greater after LTX than RTX (p = 0.039) for patients with Bismuth-Corlette IV HC. CONCLUSIONS Patients with clearly resectable de novo HC should be treated with resection because there is no evidence that they would fare better with LTX. Patients with locally unresectable de novo HC, meeting criteria for our protocol, should be treated with LTX. The decision to proceed with RTX or LTX for patients with borderline resectable de novo HC remains difficult, but our results suggest that patients with B-C type IV HC might be best treated with transplantation, if they are excellent transplant candidates.

The Use of Donation after Cardiac Death Allografts Does Not Increase Recurrence of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) recurrence in patients undergoing liver transplantation (LT) with donation after brain death (DBD) and donation after cardiac death (DCD) allografts has not previously been investigated. Rates and patterns of HCC recurrences were investigated in patients undergoing DBD (N = 1633) and DCD (N = 243) LT between 2003 and 2012. LT for HCC was identified in 397 patients (340 DBD and 57 DCD). No difference in tumor number (p = 0.26), tumor volume (p = 0.34) and serum alphafetoprotein (AFP) (p = 0.47) was seen between the groups. HCC recurrence was identified in 41 (12.1%) patients in the DBD group and 7 (12.3%) patients in the DCD group. There was no difference in recurrence‐free survival (p = 0.29) or cumulative incidence of HCC recurrence (p = 0.91) between the groups. Liver allograft was the first site of recurrence in 22 (65%) patients in the DBD group and two (37%) patients in the DCD group (p = 0.39). LT for HCC with DBD and DCD allografts demonstrate no difference in the rate of HCC recurrence. Previously published differences in survival demonstrated between recipients with HCC receiving DBD and DCD allografts despite statistical adjustment can likely be explained by practice patterns not captured by variables contained in the SRTR database.

Early allograft dysfunction after liver transplantation: An intermediate outcome measure for targeted improvements

BACKGROUND The term early allograft dysfunction (EAD) identifies liver transplant (LT) allografts with initial poor function and portends poor allograft and patient survival. Aims of this study are to use EAD as an intermediate outcome measure in a large single center cohort and identify donor, recipient and peri-operative risk factors. MATERIAL AND METHODS In 1950 consecutive primary LT, donor, recipient and peri-operative data were collected. EAD was defined by the presence of one or more of the following: total bilirubin ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST > 2,000 IU/L within the first 7 days. RESULTS The incidence of EAD was 26.5%. 1-, 3-, and 5-year allograft and patient survival for patients who developed EAD were significantly inferior to those who did not (P < 0.01 at all time points). Multivariate analysis demonstrated associations in the development of EAD with recipient pre-operative ventilator status, donation after cardiac death allografts, donor age, allograft size, degree of steatosis, operative time and intra-operative transfusion requirements (all P < 0.01). Patients with EAD had a significantly longer hospitalization at 20.9 ± 38.9 days (median: 9; range: 4-446) compared with 10.7 ± 13.5 days (median: 7; range: 3-231) in patients with no EAD (P < 0.01). CONCLUSIONS This is the largest single center experience demonstrating incidence of EAD and identifying factors associated with development of EAD. EAD is a useful intermediate outcome measure for allograft and patient survival. Balancing recipient pretransplant conditions, donor risk factors and intra-operative conditions are necessary for avoiding EAD.BACKGROUND The term early allograft dysfunction (EAD) identifies liver transplant (LT) allografts with initial poor function and portends poor allograft and patient survival. Aims of this study are to use EAD as an intermediate outcome measure in a large single center cohort and identify donor, recipient and peri-operative risk factors. MATERIAL AND METHODS In 1950 consecutive primary LT, donor, recipient and peri-operative data were collected. EAD was defined by the presence of one or more of the following: total bilirubin ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST > 2,000 IU/L within the first 7 days. RESULTS The incidence of EAD was 26.5%. 1-, 3-, and 5-year allograft and patient survival for patients who developed EAD were significantly inferior to those who did not (P < 0.01 at all time points). Multivariate analysis demonstrated associations in the development of EAD with recipient pre-operative ventilator status, donation after cardiac death allografts, donor age, allograft size, degree of steatosis, operative time and intra-operative transfusion requirements (all P < 0.01). Patients with EAD had a significantly longer hospitalization at 20.9 ± 38.9 days (median: 9; range: 4-446) compared with 10.7 ± 13.5 days (median: 7; range: 3-231) in patients with no EAD (P < 0.01). CONCLUSIONS This is the largest single center experience demonstrating incidence of EAD and identifying factors associated with development of EAD. EAD is a useful intermediate outcome measure for allograft and patient survival. Balancing recipient pretransplant conditions, donor risk factors and intra-operative conditions are necessary for avoiding EAD.

Early Allograft Dysfunction Is Associated With Excess Resource Utilization After Liver Transplantation

BACKGROUND There are limited data on length of stay (LOS) following liver transplantation (LT), yet this is an important health services metric that directly correlates with early post-LT health care costs. The primary objective of this study was to examine the relationship between early allograft dysfunction (EAD) and LOS after LT. The secondary objective was to identify additional recipient, donor, and operative factors associated with LOS. METHODS Adult patients undergoing primary LT over a 32-month period were prospectively examined at a single center. Subjects fulfilling standard criteria for EAD were compared with those not meeting the definition. Variables associated with increased LOS on ordinal logistic regression were identified. RESULTS Subjects with EAD had longer mean hospital LOS than those without (42.5 ± 38.9 days vs 27.4 ± 31 days; P = .003). Subjects with EAD also had longer mean intensive care LOS (8.61 ± 10.28 days vs 5.45 ± 11.6 days; P = .048). Additional factors significantly associated with LOS included Model for End-Stage Liver Disease (MELD) score, recipient location before LT, and postoperative surgical complications. CONCLUSIONS EAD is associated with longer hospitalization after LT. MELD score, preoperative recipient location, and postoperative complications were significantly associated with LOS. From a cost-containment perspective, these findings have implications on resource allocation.

Hepatic resection for huge (>15 cm) multinodular HCC with macrovascular invasion

BACKGROUND Surgical resection has routinely not been recommended for patients with huge (>15 cm) multinodular lesions and macrovascular invasion (advanced-stage hepatocellular carcinoma [HCC] patients) because of high operative mortality, recurrence rate, and lack of survival benefit. METHODS A retrospective study of 1425 patients was carried out, of which 1245 patients met EASL/AASLD criteria for hepatic resection (HR-EA group), 116 were surgically treated advanced-stage HCC patients (HR-AS group), and 64 were advanced-stage HCC patients receiving nonsurgical treatments (N-AS group). CONCLUSION HR may still be suitable for the HCC patients with huge (>15 cm) multinodular lesions and macrovascular invasion in selected cases. Advanced-stage HCC patients without liver cirrhosis and with a tumor-free resection margin could enjoy longer survival and lower recurrence. Preoperative and/or postoperative TACE provides no survival benefits for advanced-stage HCC patients.

IMPROVING NATIONAL RESULTS IN LIVER TRANSPLANTATION USING GRAFTS FROM DONATION AFTER CARDIAC DEATH DONORS.

Background Published reports describing the national experience with liver grafts from donation after cardiac death (DCD) donors have resulted in reservations with their widespread utilization. The present study aimed to investigate if temporal improvements in outcomes have been observed on a national level and to determine if donor and recipient selection have been modified in a fashion consistent with published data on DCD use in liver transplantation (LT). Methods Patients undergoing DCD LT between 2003 and 2014 were obtained from the United Network of Organ Sharing Standard Transplant Analysis and Research file and divided into 3 equal eras based on the date of DCD LT: era 1 (2003-2006), era 2 (2007-2010), and era 3 (2011-2014). Results Improvement in graft survival was seen between era 1 and era 2 (P = 0.001) and between era 2 and era 3 (P < 0.001). Concurrently, an increase in the proportion of patients with hepatocellular carcinoma and a decrease in critically ill patients, retransplant recipients, donor age, warm ischemia time greater than 30 minutes and cold ischemic time also occurred over the same period. On multivariate analysis, significant predictors of graft survival included: recipient age, biologic MELD score, recipient on ventilator, recipient hepatitis C virus + serology, donor age and cold ischemic time. In addition, even after adjustment for all of the aforementioned variables, both era 2 (hazard ratio, 0.81; confidence interval, 0.69-0.94; P = 0.007), and era 3 (hazard ratio, 0.61; confidence interval, 0.5-0.73; P < 0.001) had a protective effect compared to era 1. Conclusions The national outcomes for DCD LT have improved over the last 12 years. This change was associated with modifications in both recipient and donor selection. Furthermore, an era effect was observed, even after adjustment for all recipient and donor variables on multivariate analysis.