Ex Vivo Liver Resection and Autotransplantation: Should It be Used More Frequently?

OBJECTIVE: We herein advocate for more extensive utilization of ex vivo resection techniques for otherwise unresectable liver tumors by presenting the largest collective American experience. BACKGROUND: Advanced in situ resection and vascular reconstruction techniques have made R0 resection possible for otherwise unresectable liver tumors. Ex vivo liver resection may further expand the limits of resectability but remains underutilized due to concerns about technical complexity and vascular thrombosis. However, we believe that the skillset required for ex vivo liver resection is more widespread and the complications less severe than widely assumed, making ex vivo resection a more attractive option in selected case. METHODS: We retrospectively analyzed 35 cases performed by surgical teams experienced with ex vivo liver resections (at least 4 cases) between 1997 and 2021. RESULTS: We categorized malignancies as highly aggressive (n=18), moderately aggressive (n=14), and low grade (n=3). All patients underwent total hepatectomy, vascular reconstruction and resection in hypothermia on the backtable, and partial liver autotransplantation. Overall survival was 67%/39%/28%, at 1/3/5 years, respectively, with a median survival of 710 days (range: 22-4824). Patient survival for highly aggressive, moderately aggressive, and low-grade tumors was 61%/33%/23%, 67%/40%/22%, and 100%/100%/100% at 1/3/5 years, respectively, with median survival 577 days (range: 22-3873), 444 days (range: 22-4824), and 1825 days (range: 868-3549). CONCLUSIONS: Ex vivo resection utilizes techniques commonly practiced in partial liver transplantation, and we demonstrate relatively favorable outcomes in our large collective experience. Therefore, we propose that more liberal use of this technique may benefit selected patients in centers experienced with partial liver transplantation.

Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria.

BACKGROUND AND AIMS: The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013). APPROACH AND RESULTS: Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P < 0.001). CONCLUSIONS: In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.

Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma: Analysis From the US Multicenter HCC Transplant Consortium.

OBJECTIVE: The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). BACKGROUND: LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study. METHODS: Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression. RESULTS: Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67). CONCLUSIONS: For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.

Impact of Pretransplant Bridging Locoregional Therapy for Patients With Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation: Analysis of 3601 Patients From the US Multicenter HCC Transplant Consortium.

OBJECTIVE: To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC). SUMMARY BACKGROUND DATA: Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited. METHODS: Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013). RESULTS: Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044). CONCLUSIONS: Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.

The effects of Share 35 on the cost of liver transplantation.

On June 18, 2013, the United Network for Organ Sharing (UNOS) instituted a change in the liver transplant allocation policy known as "Share 35." The goal was to decrease waitlist mortality by increasing regional sharing of livers for patients with a model for end-stage liver disease (MELD) score of 35 or above. Several studies have shown Share 35 successful in reducing waitlist mortality, particularly in patients with high MELD. However, the MELD score at transplant has increased, resulting in sicker patients, more complications, and longer hospital stays. Our study aimed to explore factors, along with Share 35, that may affect the cost of liver transplantation. Our results show Share 35 has come with significantly increased cost to transplant centers across the nation, particularly in regions 2, 5, 10, and 11. Region 5 was the only region with a median MELD above 35 at transplant, and cost was significantly higher than other regions. Several other recipient factors had changes with Share 35 that may significantly affect the cost of liver transplant. While access to transplantation for the sickest patients has improved, it has come at a cost and regional disparities remain. Financial implications with proposed allocation system changes must be considered.

Combined liver transplant and pancreaticoduodenectomy for inflammatory hilar myofibroblastic tumor: Case report and review of the literature.

IMT, previously known as IPT, is a relatively rare tumor that was originally described in the lungs, but case reports have reported the tumor in almost every organ system. Surgical resection is typically the mainstay of therapy; however, tumors have also been shown to respond to chemotherapy or anti-inflammatory therapy and some have spontaneously regressed. We present a literature review and case report representing the first documentation to date of liver transplant combined with PD for surgical resection of a myofibroblastic tumor non-responsive to medical therapy.

Liver Resection and Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria.

OBJECTIVES: To assess survival after liver resection and transplantation in patients with hepatocellular carcinoma (HCC) beyond Milan criteria. BACKGROUND: The role of liver resection and transplantation remains controversial for patients with HCC beyond Milan criteria. Resection of advanced tumors and transplantation using extended-criteria are pursued at select high-volume center. METHODS: Patients from 5 liver cancer centers in the United States who had liver resection or transplantation for HCC beyond Milan criteria between 1990 and 2011 were included in the study. Multivariable and propensity-matching analyses estimated the effects of clinical factors and operative selection on survival. RESULTS: Of 608 patients beyond Milan without vascular invasion, 480 (79%) patients underwent resection and 128 (21%) underwent transplantation. Clinicopathologic profiles between resection and transplant patients differed significantly. Hepatitis C and cirrhosis were more prevalent in transplantation group (P < 0.001). Resection patients had larger tumors [median 9 cm, interquartile range (IQR): 6.5-12.9 cm vs. median 4.1, IQR: 3.4-5.3 cm, P < 0.001]; transplant patients were more likely to have multiple tumors (78% vs 28%, P < 0.001).Overall (OS) and disease-free survival (DFS) were both greater after tumor downstaging and transplantation than resection (all P < 0.001). OS did not differ between liver transplant recipients who were not pretreated or pretreated and failed to downstage compared with propensity-matched liver resection patients (P ≥ 0.176); DFS in this propensity matched cohort was greater after liver transplantation (P ≤ 0.017). CONCLUSIONS: Liver resection and transplantation provide curative options for patients with HCC beyond Milan criteria. Further treatment strategies aimed at the efficiency and durability of tumor downstaging and expansion of the role of transplantation among suitable candidates could improve outcomes in patients with large or multifocal HCC.

Diagnostic Accuracy of Preoperative Gadoxetic Acid-enhanced 3-T MR Imaging for Malignant Liver Lesions by Using Ex Vivo MR Imaging-matched Pathologic Findings as the Reference Standard.

PURPOSE: To determine per-lesion sensitivity and positive predictive value (PPV) of gadoxetic acid-enhanced 3-T magnetic resonance (MR) imaging for the diagnosis of malignant lesions by using matched (spatially correlated) hepatectomy pathologic findings as the reference standard. Materials and METHODS: In this prospective, institutional review board-approved, HIPAA-compliant study, 20 patients (nine men, 11 women; mean age, 59 years) with malignant liver lesions who gave written informed consent underwent preoperative gadoxetic acid-enhanced 3-T MR imaging for surgical planning. Two image sets were independently analyzed by three readers to detect liver lesions (set 1 without and set 2 with hepatobiliary phase [HBP] images). Hepatectomy specimen ex vivo MR imaging assisted in matching gadoxetic acid-enhanced 3-T MR imaging findings with pathologic findings. Interreader agreement was assessed by using the Cohen κ coefficient. Per-lesion sensitivity and PPV were calculated. RESULTS: Cohen κ values were 0.64-0.76 and 0.57-0.84, and overall per-lesion sensitivity was 45% (42 of 94 lesions) to 56% (53 of 94 lesions) and 58% (55 of 94 lesions) to 64% (60 of 94 lesions) for sets 1 and 2, respectively. The addition of HBP imaging did not affect interreader agreement but significantly improved overall sensitivity for one reader (P < .05) and almost for another (P = .05). Sensitivity for 0.2-0.5-cm lesions was 0% (0 of 26 lesions) to 8% (two of 26 lesions) for set 1 and 4% (one of 26 lesions) to 12% (three of 26 lesions) for set 2. Sensitivity for 0.6-1.0-cm lesions was 28% (nine of 32 lesions) to 59% (19 of 32 lesions) for set 1 and 66% (21 of 32 lesions) to 69% (22 of 32 lesions) for set 2. Sensitivity for lesions at least 1.0 cm in diameter was at least 81% (13 of 16 lesions) for set 1 and was not improved for set 2. PPV was 98% (56 of 57 lesions) to 100% (60 of 60 lesions) for all readers without differences between image sets or lesion size. CONCLUSION: Gadoxetic acid-enhanced 3-T MR imaging provides high per-lesion sensitivity and PPV for preoperative malignant liver lesion detection overall, although sensitivity for 0.2-0.5-cm malignant lesions is poor.

Kidney clamp, perfuse, re-implant: a useful technique for graft salvage after vascular complications during kidney transplantation.

Although intra-operative vascular complications during renal transplantation are rare, injuries associated with prolonged ischemia may lead to graft threatening early and late complications. This series describes a novel technique for intra-operative repair of vascular complications in five patients over a three-yr period. The method consists of rapid graft nephrectomy and re-preservation of the graft with cold University of Wisconsin solution, which allows for controlled/precise back table repair of the vascular injury without incurring prolonged warm ischemia time. In three cases, the donor renal vein (2) and donor renal artery (1) were damaged and required back table reconstruction. In two cases, the recipient iliac artery needed reconstruction. Three of the five cases used deceased donor iliac vessels from another donor for reconstruction. Two patients required postoperative dialysis for delayed graft function for three to nine d (average six d) and two patients had slow graft function. All grafts were functioning at 17 months (mean) after transplant, with a median serum of 1.61 mg/dL (0.74-3.69). This series demonstrates the effectiveness of kidney clamp, perfuse, resuscitate as an effective intra-operative technique to salvage grafts after vascular injury. Although the grafts may suffer from delayed or slow graft function, excellent long-term function is attainable.

ECD kidney transplantation outcomes are improved when matching donors to recipients using a novel creatinine clearance match ratio (CCMR).

Improved outcomes have been associated with various methods of size matching between expanded criteria (ECD) donors and recipients. A novel method for improved functional based matching was developed utilizing manipulation of Cockcroft-Gault estimated creatinine clearances for donor and recipient. We hypothesized that optimal clearance-based matches would have superior outcomes for both immediate graft function and long-term graft survival. For the analysis, recipients of ECD kidneys in the Scientific Registry of Transplant Recipients (SRTR) transplanted between October 1, 1987 and August 31, 2011 were included. Univariate and multivariate analyses predicted the hazard ratio of graft failure and the odds ratio of requiring dialysis within the first week. A total of 25,640 ECD kidney transplants were analyzed. On multivariate analysis, higher creatinine clearance match ratio (CCMR) was associated with increased graft failure and odds of requiring dialysis within the first week (comparing highest ratio quintile versus lowest ratio quintile: HR 1.43, p < 0.001; OR 2.08, p < 0.001). This study suggests that ECD kidneys have improved outcomes when the recipient/donor CCMR is optimized.

Does the Surgical Approach Affect the Incidence of Post-Hepatectomy Liver Failure in Cirrhotic Patients? An Analysis of the NSQIP Database.

Background: The association between surgical approach and post-hepatectomy liver failure (PHLF) in cirrhotic patients is poorly understood. We hypothesize that patients will have similar rates of liver failure regardless of whether they undergo minimally invasive liver resection (MILR) or open liver resection (OLR) in major liver resections. In contrast, there will be lower rates of PHLF in patients undergoing minor hepatectomy via the MILR approach.Methods: Propensity score matching was used to analyze regression by matching the MILR to the OLR cohort. Patient demographics from the American College of Surgeons National Surgical Quality Improvement Program, including race, age, gender, and ethnicity, were matched. Chronic obstructive pulmonary disease, congestive heart failure, smoking, hypertension, diabetes, renal failure, dyspnea, dialysis dependence, body mass index, and American Society of Anesthesiologists (ASA) classification (>ASA III) were among the preoperative patient characteristics subject to matching. PHLF (Grade A vs B. vs C) was our primary outcome measure.Results: A total of 2129 cirrhotic patients were included in the study. In the minor hepatectomy group, patients undergoing an OLR were more likely to get discharged to a facility (7.0% vs 4.4%; P = .03), had greater hospital length of stay (5 vs 3 days; P = .02), and had a greater need for invasive postoperative interventions (10.7% vs 4.6%; P < .01). They were also noted to have higher rates of organ space superficial surgical infections (SSIs) (7.3% vs 3.7%; P = .003), Clostridium difficile infection (.9% vs .1%; P = .05), renal insufficiency (2.1% vs .1%; P < .01), unplanned intubations (3.1% vs 1.4%; P = .03), and Grade C liver failure (2.3% vs .9%; P = .03).Conclusion: A higher incidence of PHLF grade C was found in patients undergoing OLR in the minor hepatectomy group. Therefore, in cirrhotic patients who can tolerate minimally invasive approaches, MILR should be offered to prevent postoperative complications as part of their optimization plan.

Liver transplant versus liver resection in patients with multifocal hepatocellular carcinoma.

BACKGROUND: The optimal surgical option in patients with multifocal hepatocellular carcinoma (MHCC) is an area of active research. The preference varies based on geographic variations and institutional policies. We sought to determine long-term outcomes in patients with MHCC based on surgical treatment-liver transplant (LT) vs resection (LR). METHODS: We performed a retrospective analysis of the National Cancer Database (2004-2015) and identified patients with MHCC within Milan criteria. Patients with α-fetoprotein ≥ 1000 ng/mL and those who underwent ablation were excluded. The primary outcome measure was long-term survival in patients undergoing LT vs LR. The secondary aim of our study was to determine clinicodemographic factors associated with the receipt of LT and LR. RESULTS: A total of 1546 patients were included, of whom 1211 received LT and 335 underwent LR. Patients who were non-Hispanic White (70.8% vs 54.9%; P < .01), privately insured (53.7% vs 36.7%; P < .01), and treated at academic centers (85.4% vs 71.6%; P < .01) were more likely to receive an LT. Multivariable Cox analysis revealed LT was associated with improved survival compared with LR (hazard ratio, 0.34; 95% CI, 0.28-0.42). CONCLUSION: We described clinical and sociodemographic differences in LT and LR patients and found LT to be associated with a decreased mortality risk compared with LR. The study's findings should be interpreted in the context of several limitations, including the selection of MHCC criteria within Milan criteria.

Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multicenter collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA. STUDY DESIGN: Liver transplant and resection outcomes for HCC (n = 2,998) and cHCC-CCA (n = 208) were compared in a 12-center retrospective review (2009 to 2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis. RESULTS: Liver transplantation for cHCC-CCA (n = 67) and HCC (n = 1,814) within Milan had no significant difference in overall survival (5-year cHCC-CCA 70.1%, HCC 73.4%, p = 0.806), despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5 years, p < 0.001). Irrespective of tumor burden, cHCC-CCA tumor patient undergoing liver transplant had significantly superior overall survival (p = 0.047) and disease-free survival (p < 0.001) than those having resection. For cHCC-CCA within Milan, liver transplant was associated with improved disease-free survival over resection (70.3% vs 33.6% 5 years, p < 0.001). CONCLUSIONS: Regardless of tumor burden, outcomes after liver transplantation are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC result in similar overall survival, justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population.

Braun enteroenterostomy is associated with reduced delayed gastric emptying and early resumption of oral feeding following pancreaticoduodenectomy.

BACKGROUND AND OBJECTIVES: Morbidity rates following pancreaticoduodenectomy (PD) remain high with delayed gastric emptying (DGE) and slow resumption of oral diet contributing to increased postoperative length of stay. A Braun enteroenterostomy has been shown to decrease bile reflux following gastric resection. We hypothesize that addition of Braun enteroenterostomy during PD would reduce the sequelae of DGE. METHODS: From our PD database, patients were identified that underwent classic PD with partial gastrectomy from 2001 to 2006. All patients with reconstruction utilizing a single loop of jejunum at the University of Florida Shands Hospital were reviewed. Demographics, presenting signs and symptoms, pathologic diagnoses, and postoperative morbidity were compared in those patients undergoing reconstruction with an additional Braun enteroenterostomy (n = 70) to those not undergoing a Braun enteroenterostomy (n = 35). RESULTS: Patients undergoing a Braun had NG tubes removed earlier (Braun: 2 days, no Braun: 3 days, P = 0.002) and no significant change in postoperative vomiting (Braun: 27%, no Braun: 37%, P = 0.37) or NG tube reinsertion rates (Braun: 17%, no Braun: 29%, P = 0.21). Median postoperative day with tolerance of oral liquids (Braun: 5, no Braun: 6, P = 0.01) and solid diets (Braun: 7, no Braun: 9, P = 0.01) were significantly sooner in the Braun group. DGE defined by two criteria including the inability to have oral intake by postoperative day 10 (Braun: 10%, no Braun: 26%, P < 0.05) and the international grading criteria (grades B and C, Braun: 7% vs. no Braun: 31%, P = 0.003) were significantly reduced in those undergoing the Braun procedure. In addition, the median length of stay (Braun: 10 days, no Braun: 12 days, P < 0.05) was significantly reduced in those undergoing the Braun procedure. The rate of pancreatic anastomotic failure was similar in the two groups (Braun: 17% vs. no Braun: 14%, P = 0.79). Median bile reflux was 0% in those undergoing a Braun. CONCLUSIONS: The present study suggests that Braun enteroenterostomy can be safely performed in patients undergoing PD and may reduce the indicence of DGE and its sequelae. Further studies of Braun enteroenterostomy in larger randomized trials of patients undergoing PD are warranted.

Major hepatectomy induces phenotypic changes in circulating dendritic cells and monocytes.

INTRODUCTION: Patients undergoing major hepatectomy are at increased risk for post-operative morbidity and mortality, and changes in the phenotype of effector cells may predispose these patients to infectious sequelae. METHODS: To better understand post-hepatectomy immune responses, peripheral blood from 15 hepatectomy patients was drawn immediately before and after liver resection and on post-operative days 1, 3, and 5. Circulating monocytes and dendritic cells were analyzed by flow cytometry for quantity, phenotype, activation status, human leukocyte antigen DR (HLA-DR) expression, and toll-like receptor-2 and -4 expression. RESULTS: Major hepatectomy increased the numbers of activated CD16(bright) blood monocytes and the percentage of activated dendritic cells, although monocyte HLA-DR expression was reduced. These results may represent both dysfunctional antigen presentation and pending anergy, as well as cellular priming of immune effector cells. Better understanding of the alterations in innate immunity induced by hepatectomy may identify strategies to reduce infectious outcomes.

Development of quality indicators of care for patients undergoing hepatic resection for metastatic colorectal cancer using a Delphi process.

BACKGROUND: Very few quality indicators of care exist for surgical procedures. These may be used to both score the quality of care received, and as a method of improving the quality of care delivered (quality improvement initiatives). MATERIALS AND METHODS: The goal of this study was to develop a set of evidence-based quality indicators by expert consensus for patients undergoing hepatic resection of colorectal metastases to the liver. A Delphi approach was used to develop a set of evidence-based quality indicators for patients undergoing hepatic resection of colorectal metastases to liver. A panel of experts was formed through nomination by members of the Canadian Hepatopancreaticobiliary Society (CHPBS). The Delphi process consisted of three iterations of questionnaires. During each round, the panel members were asked to score the potential indicators and suggest any new indicators. RESULTS: A list of 70 potential indicators was generated from the literature, of which 27 achieved consensus for inclusion in the final list of quality indicators. After consolidating similar or redundant indicators, the final list had 18 quality indicators. All of the indicators in the final list were from our original literature search. CONCLUSIONS: This Delphi process has used the best available evidence, along with a consensus methodology employing the opinion of experts in the field, to identify 18 quality indicators for patients undergoing hepatic resection for metastatic colorectal cancer. These indicators will provide a means for benchmarking quality of care among surgeons, institutions, and health regions.

Primary human hepatocyte culture for HCV study.

Studies of HCV pathogenesis and antiviral research have been hampered by the lack of adequate cell-culture and small-animal models. The culturing of human primary hepatocytes would greatly facilitate the model development in HCV research. The availability of robust infectious virus, JFH1 (i.e., genotype 2) strain, will further increase the interest in using primary hepatocyte cultures. This cell model system will significantly enhance research in the areas of antiviral research and host-virus interaction, but obtaining pure and viable human primary hepatocytes is not trivial. We have optimized a method of liver perfusion and primary hepatocyte isolation that allows us to establish robust and reliable human primary hepatocyte cultures. Moreover, we have demonstrated that these primary cultures are susceptible to authentic HCV infection in vitro.