Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment.

UNLABELLED: The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that "very early" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with "very early" iCCA and those with "advanced" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the "very early" iCCA group and 33/48 (69%) the "advanced" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the "advanced" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).

Three-point transfusion risk score in hepatectomy.

BACKGROUND: Perioperative red blood cell transfusions are required in up to 23 per cent of patients undergoing hepatectomy. Previous research has developed three transfusion risk scores to assess risk of perioperative red blood cell transfusion. Here, the performance of these transfusion risk scores was evaluated in a multicentre cohort of patients who underwent hepatectomy and compared with that of a simplified transfusion risk score. METHODS: A database of patients undergoing hepatectomy at four specialized centres between 2008 and 2012 was developed. External validity was assessed by discrimination and calibration. Discrimination was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). Calibration was evaluated by the degree of agreement between predicted and actual red blood cell transfusion probabilities. A simplified transfusion risk score using variables common to the three models was created, and discrimination and calibration were evaluated. RESULTS: There were 1287 patients included in this study, with 341 (26·5 per cent) receiving a red blood cell transfusion. Discriminative ability was similar between the three transfusion risk scores, with AUCs of 0·66-0·68 and good calibration. A new three-point risk score was developed based on factors present in all models: haemoglobin 12·5 g/dl or less, primary liver malignancy and major resection (at least 4 segments). Discriminative ability and calibration of the three-point model were similar to those of the three existing models, with an AUC of 0·66. CONCLUSION: The three-point transfusion risk score simplifies assessment of perioperative transfusion risk in hepatectomy without sacrificing predictive ability.

Should ALPPS be Used for Liver Resection in Intermediate-Stage HCC?

BACKGROUND: Extended liver resections in patients with hepatocellular carcinoma (HCC) are problematic due to hepatitis, fibrosis, and cirrhosis. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has been promoted as a novel method to induce hypertrophy for patients with extensive colorectal liver metastases, but outcomes in HCC have not been well investigated. METHODS: All patients registered in the international ALPPS Registry ( www.alpps.org ) from 2010 to 2015 were studied. Hypertrophy of the future liver remnant, perioperative morbidity and mortality, age, overall survival, and other parameters were compared between patients with HCC and patients with colorectal liver metastases (CRLM). RESULTS: The study compared 35 patients with HCC and 225 patients with CRLM. The majority of patients undergoing ALPPS for HCC fall into the intermediate-stage category of the Barcelona clinic algorithm. In this study, hypertrophy was rapid and extensive for the HCC patients, albeit lower than for the CRLM patients (47 vs. 76 %; p < 0.002). Hypertrophy showed a linear negative correlation with the degrees of fibrosis. The 90-day mortality for ALPPS used to treat HCC was almost fivefold higher than for CRLM (31 vs. 7 %; p < 0.001). Multivariate analysis showed that patients older than 61 years had a significantly reduced overall survival (p < 0.004). CONCLUSION: The ALPPS approach induces a considerable hypertrophic response in HCC patients and allows resection of intermediate-stage HCC, albeit at the cost of a 31 % perioperative mortality rate. The use of ALPPS for HCC remains prohibitive for most patients and should be performed only for a highly selected patient population younger than 60 years with low-grade fibrosis.

Spontaneous clearance of hepatitis C after liver and renal transplantation.

Spontaneous clearance of hepatitis C virus (HCV) is rare in immunocompromised patients, such as those who have undergone organ transplantation. It has been recognized that patients receiving liver transplantation for HCV-related disease have decreased graft and patient survival compared with those transplanted for other etiologies. There is a growing trend toward treating HCV recurrence aggressively after liver transplantation. For other organ transplant recipients with concurrent HCV, treatment is not often an option, given the high rates of graft rejection and loss secondary to interferon and its immunomodulatory effects. Although spontaneous clearance of HCV has been reported in recipients of solitary liver and renal transplants, a common factor arising in these cases has been previous exposure to interferon. To date, no reports of spontaneous clearance of HCV RNA have been reported in a multiorgan transplant recipient. A case of spontaneous clearance of HCV RNA in an immunocompromised patient, within five months of simultaneous liver and kidney retransplantation is described. Importantly, this patient had no previous exposure to interferon.

Non-operative management of blunt hepatic trauma: Does angioembolization have a major impact?

PURPOSE: A paradigm shift toward non-operative management (NOM) of blunt hepatic trauma has occurred. With advances in percutaneous interventions, even severe liver injuries are being managed non-operatively. However, although overall mortality is decreased with NOM, liver-related morbidity remains high. This study was undertaken to explore the morbidity and mortality of blunt hepatic trauma in the era of angioembolization (AE). METHODS: A retrospective cohort of trauma patients with blunt hepatic injury who were assessed at our centre between 1999 and 2011 were identified. Logistic regression was undertaken to identify factors increasing the likelihood of operative management (OM) and mortality. RESULTS: We identified 396 patients with a mean ISS of 33 (± 14). Sixty-two (18%) patients had severe liver injuries (≥ AAST grade IV). OM occurred in 109 (27%) patients. Logistic regression revealed high ISS (OR 1.07; 95% CI 1.05-1.10), and lower systolic blood pressure on arrival (OR 0.98; 95% CI 0.97-0.99) to be associated with OM. The overall mortality was 17%. Older patients (OR 1.05; 95% CI 1.03-1.07), those with high ISS (OR 1.11; 95% CI 1.08-1.14) and those requiring OM (OR 2.89; 95% CI 1.47-5.69) were more likely to die. Liver-related morbidities occurred in equal frequency in the OM (23%) and AE (29%) groups (p = 0.32). Only 3% of those with NOM experienced morbidity. CONCLUSIONS: The majority of patients with blunt hepatic trauma can be successfully managed non-operatively. Morbidity associated with NOM was low. Patients requiring AE had morbidity similar to OM.

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.

Salvage parenchymal liver transection for patients with insufficient volume increase after portal vein occlusion -- an extension of the ALPPS approach.

BACKGROUND: Portal vein ligation (PVL) or embolization (PVE) are standard approaches to induce liver hypertrophy of the future liver remnant (FLR) prior to hepatectomy in primarily non-resectable liver tumors. However, this approach fails in about one third of patients. Recently, the new "ALPPS" approach has been described that combines PVL with parenchymal transection to induce rapid liver hypertrophy. This series explores whether isolated parenchymal transection boosts liver hypertrophy in scenarios of failed PVL/PVE. METHODS: A multicenter database with 170 patients undergoing portal vein manipulation to increase the size of the FLR was screened for patients undergoing isolated parenchymal transection as a salvage procedure. Three patients who underwent PVL/PVE with subsequent insufficient volume gain and subsequently underwent parenchymal liver transection as a salvage procedure were identified. Patient characteristics, volume increase, postoperative complications and outcomes were analyzed. RESULTS: The first patient underwent liver transection 16 weeks after failed PVL with a standardized FLR (sFLR) of 30%, which increased to 47% in 7 days. The second patient showed a sFLR of 25% 28 weeks after PVL and subsequent PVE of segment IV, which increased to 41% in 7 days after transection. The third patient underwent liver partition 8 weeks after PVE with a sFLR of 19%, which increased to 37% in six days. All patients underwent a R0 resection. CONCLUSION: Failed PVE or PVL appears to represent a good indication for the isolated parenchymal liver transection according to the newly developed ALPPS approach.

Pancreas-sparing duodenectomy for an obstructive adenocarcinoma of the duodenum.

A duodenal adenocarcinoma arising from the junction of the second and third portion of the duodenum, which was resected by pancreas-sparing duodenectomy, is reported. The completely obstructing tumour was circumferential and measured 6.5cm x 3.5cm x 1.0 cm. There was no evidence of pancreas invasion, nor any lymph node metastasis. Pancreas-sparing duodenectomy was performed, with dissection of the pancreaticoduodenal lymph nodes. The proximal duodenum was transected just distal to the ampula of Vater and jejunum was transected just distal to the ligament of Treitz. A hand-sewn side-to-side anastomosis for the duodenojejunostomy was performed. There were no postoperative complications. Pathology reported a duodenal adenocarcinoma resected with negative margins. Pancreaticoduodenectomy is the treatment of choice for a duodenal adenocarcinoma, however, pancreas-sparing duodenectomy may be a safe alternative for duodenal tumours not involving the 2(nd) portion, especially in elderly patients with multiple medical comorbidities.

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.