Salvage versus Primary Liver Transplantation for Hepatocellular Carcinoma: A Twenty-Year Experience Meta-Analysis.

(1) Background: Primary liver transplantation (PLT) for HCC represents the ideal treatment. However, since organ shortage increases the risk of drop-out from the waiting list for tumor progression, a new surgical strategy has been developed: Salvage Liver Transplantation (SLT) can be offered as an additional curative strategy for HCC recurrence after liver resection. The aim of this updated meta-analysis is to compare surgical and long-term outcomes of SLT versus PLT for HCC. (2) Materials and Methods: A systematic review and meta-analysis was conducted using the published papers comparing SLT and PLT up to January 2022. (3) Results: 25 studies describing 11,275 patients met the inclusion criteria. The meta-analysis revealed no statistical difference in intraoperative blood loss, overall vascular complications, retransplantation rate, and hospital stay in the SLT group compared with the PLT group. However, the SLT group showed a slightly significant lower 5-year OS rate and 5-year disease-free survival rate. (4) Conclusion: meta-analysis advocates the relative safety and feasibility of both Salvage LT and Primary LT strategies. Specifically, SLT seems to have comparable surgical outcomes but slightly poorer long-term survival than PLT.

Cytokine mass balance levels in donation after circulatory death donors using hemoadsorption: Case series report.

The use of hemadsorption has been purposed to reduce cytokine levels during the reperfusion phase during donation after circulatory death (DCD) programs. This paper aims to describe a cases series of the inflammatory cytokine levels before and after hemadsorption during normothermic reperfusion in DCD donors of liver and kidneys. In this observational pilot paper, we describe 8 DCD donors of liver or kidneys in our center from the year 2018 to 2019. All DCD donor subjects had similar age, were younger than 60 years, without evident critical conditions, no liver or kidney dysfunction known, and they presented with poor neurological outcomes instrumentally and clinically documented. We observed in our patients an interesting reduction of IL-10 and TNF-α levels during the normothermic reperfusion with hemadsorption. We transplanted all livers and kidneys from DCD donors without significant compliances.

A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation.

BACKGROUND & AIMS: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. METHODS: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups and to provide a valid comparator cohort for future clinical trials. LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort.

How to Preserve Liver Grafts From Circulatory Death With Long Warm Ischemia? A Retrospective Italian Cohort Study With Normothermic Regional Perfusion and Hypothermic Oxygenated Perfusion.

BACKGROUND: Donation after circulatory death (DCD) in Italy, given its 20-min stand-off period, provides a unique bench test for normothermic regional perfusion (NRP) and dual hypothermic oxygenated machine perfusion (D-HOPE). METHODS: We coordinated a multicenter retrospective Italian cohort study with 44 controlled DCD donors, who underwent NRP, to present transplant characteristics and results. To rank our results according to the high donor risk, we matched and compared a subgroup of 37 controlled DCD livers, preserved with NRP and D-HOPE, with static-preserved controlled DCD transplants from an established European program. RESULTS: In the Italian cohort, D-HOPE was used in 84% of cases, and the primary nonfunction rate was 5%. Compared with the matched comparator group, the NRP + D-HOPE group showed a lower incidence of moderate and severe acute kidney injury (stage 2: 8% versus 27% and stage 3: 3% versus 27%; P = 0.001). Ischemic cholangiopathy remained low (2-y proportion free: 97% versus 92%; P = 0.317), despite the high-risk profile resulting from the longer donor warm ischemia in Italy (40 versus 18 min; P < 0.001). CONCLUSIONS: These data suggest that NRP and D-HOPE yield good results in DCD livers with prolonged warm ischemia.

Robotic Liver Resection Versus Percutaneous Ablation for Early HCC: Short- and Long-Term Results.

BACKGROUND: The correct approach for early hepatocellular carcinoma (HCC) is debatable, since multiple options are currently available. Percutaneous ablation (PA) is associated in some series to reduced morbidity compared to liver resection (LR); therefore, minimally invasive surgery may play a significant role in this setting. METHODS: All consecutive patients treated by robotic liver resection (RLR) or PA between January 2014 and October 2019 for a newly diagnosed single HCC, less than 3 cm in size (very early/early stages according to the Barcelona Clinic Liver Cancer (BCLC)) on chronic liver disease or liver cirrhosis, were enrolled in this retrospective study. The aim of this study was to compare short- and long-term outcomes to define the best approach in this specific cohort. RESULTS: 60 patients fulfilled the inclusion criteria: 24 RLR and 36 PA. The two populations were homogeneous in terms of baseline characteristics. There were no statistically significant differences regarding the incidence of postoperative morbidity (RLR 38% vs. PA 19%, p = 0.15). The cumulative incidence of recurrence (CIR) was significantly higher in patients who underwent PA, with the one, two, and three years of CIR being 42%, 69%, and 73% in the PA group and 17%, 27%, and 27% in the RLR group, respectively. CONCLUSIONS: RLR provides a significantly higher potential of cure and tumor-related free survival in cases of newly diagnosed single HCCs smaller than 3 cm. Therefore, it can be considered as a first-line approach for the treatment of patients with those characteristics in high-volume centers with extensive experience in the field of hepatobiliary surgery and minimally invasive approaches.

Robotic versus laparoscopic gastrectomy for gastric cancer: The largest meta-analysis.

BACKGROUND: Minimally invasive surgery (MIS) has been increasingly used in the treatment of gastric cancer (GC). Laparoscopic gastrectomy (LG) has shown several advantages over open surgery in dealing with GC, although it is still considered a demanding procedure. Robotic gastrectomy (RG) is now being employed with increased frequency worldwide and has been reported to overcome some limitations of conventional LG. The aim of this updated meta-analysis is to compare surgical and oncological outcomes of RG versus LG for gastric cancer. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted using the PubMed, MEDLINE and Cochrane library database of published studies comparing RG and LG up to March 2020. The evaluated end-points were intra-operative, post-operative and oncological outcomes. Dichotomous data were calculated by odds ratio (OR) and continuous data were calculated by mean difference (MD) with 95% confidence intervals (95% CI), and a random-effect model was always applied. RESULTS: Forty retrospective studies describing 17,712 patients met the inclusion criteria. With respect to surgical outcomes, robotic compared with laparoscopic gastrectomy was associated with higher operating time [MD 44.73, (95%CI 36.01, 53.45) p < 0.00001] and less intraoperative blood loss [MD -18.24, (95%CI -25.21, -11.26) p < 0.00001] and lower rate of surgical complication in terms of Dindo-Clavien ≥ 3 classification [OR 0.66, (95%CI 0.49, 0.88) p = 0.005]. With respect to oncological outcomes, the RG group showed a significantly increased mean number of retrieved lymph nodes [MD 1.84, (95%CI 0.84, 2.84) p = 0.0003], but mean proximal and distal resection margin distance and the recurrence rate were not significantly different between the two approaches. CONCLUSIONS: With respect to safety, technical feasibility and oncological adequacy, robotic and laparoscopic groups were comparable, although the robotic approach seems to achieve better short-term surgical outcomes. Moreover, a higher rate of retrieved lymph nodes was observed in the RG group.

Pre-transplant diabetes predicts atherosclerotic vascular events and cardiovascular mortality in liver transplant recipients: a long-term follow-up study.

Background Early after surgery, liver transplant (LT) recipients often develop weight gain. Metabolic disorders and cardiovascular disease represent main drivers of morbidity and mortality. Our aim was to identify predictors of atherosclerotic vascular events (AVE) and to assess the impact of AVE on the long-term outcome. Methods We retrospectively analyzed data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics. Cox Regression analysis was performed to identify predictors of AVE, global mortality, and cardiovascular mortality. Survival analysis was performed using the Kaplan-Meier method. Results We analyzed data from 367 subjects during a median follow-up of 14 years. Thirty-seven post-LT AVE were registered. Patients with AVE more frequently showed pre-LT diabetes mellitus (DM) (48.6 vs 13.9%, p=0.000). In the post-LT period, patients with AVE satisfied criteria of metabolic syndrome in 83.8% vs. 36.7% of subjects without AVE (p=0.000). At multivariate analysis, pre-LT DM independently predicted AVE (HR 2.250, CI 4.848-10.440, p=0.038). Moreover, both pre-LT DM and AVE strongly predicted cardiovascular mortality (HR 5.418, CI 1.060-29.183, p=0.049, and HR 86.097, CI 9.510-779.480, p=0.000, respectively). Conclusions Pre-LT DM is the main risk factor for post-LT AVE. Pre-LT DM and post-LT AVE are strong, long-term predictors of cardiovascular mortality. Patients with pre-LT DM should obtain a personalized follow-up for prevention or early diagnosis of AVE.

Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: the first meta-analysis.

BACKGROUND: Laparoscopic liver resection (LLR) has gained increasing acceptance for surgical treatment of malignant and benign liver tumors. LLR for intrahepatic cholangiocarcinoma (ICC) is not commonly performed because of the concern for the frequent need for major hepatectomy, vascular-biliary reconstructions, and lymph node dissection (LND). The aim of this present meta-analysis is to compare surgical and oncological outcomes of laparoscopic (LLR) versus open liver resection (OLR) for ICC. MATERIALS AND METHODS: A systematic review was conducted using the PubMed, MEDLINE, and Cochrane library database of published studies comparing LLR and OLR up to October 2019. Two reviewers independently assessed the eligibility and quality of the studies. Dichotomous data were calculated by odds ratio (OR), and continuous data were calculated by mean difference (MD) with 95% confidence intervals (95% CI). RESULTS: Four retrospective observational studies describing 204 patients met the inclusion criteria. With respect to surgical outcomes, laparoscopic compared with open liver resection was associated with lower blood loss [MD - 173.86, (95% CI - 254.82, -92.91) p < 0.0001], less requirement of blood transfusion [OR 0.34, (95% CI 0.14, 0.82) p = 0.02], less need for Pringle maneuver [OR 0.17, (95% CI 0.07, 0.43) p = 0.0002], shorter hospital stay [MD - 3.77, (95% CI - 5.09, - 2.44; p < 0.0001], and less morbidity [OR 0.44, (95% CI 0.21, 0.94) p = 0.03]. With respect to oncological outcomes, the LLR group was prone to lower rates of lymphadenectomy [OR 0.12, (95% CI 0.06, 0.25) p < 0.0001], but surgical margins R0 and recurrence rate were not significantly different. CONCLUSION: Laparoscopic liver resection for ICC seems to achieve better surgical outcomes, providing short-term benefits without negatively affecting oncologic adequacy in terms of R0 resections and disease recurrence. However, a higher LND rate was observed in the open group. Due to the risk of bias and the statistical heterogeneity between the studies included in this review, further RCTs are needed to reach stronger scientific conclusions.

University of Modena Experience With Liver Grafts From Donation After Circulatory Death: What Really Matters in Organ Selection?

INTRODUCTION: The use of grafts from donation after circulatory death (DCD) is an important additional source to implement within the donor pool. We herein report the outcomes of our early experience with DCD grafts for liver transplantation (LT). METHODS: Ten patients successfully underwent LT with grafts from DCD donors between August 2017 and January 2019 at the Hepato-Pancreato-Biliary Surgery and Liver Transplant Unit of University of Modena and Reggio Emilia. All donors underwent normothermic regional perfusion after death declaration and, after the procurement, all the suitable grafts underwent ex situ hypothermic perfusion prior to transplantation. RESULTS: Mean postoperative hospital stay after transplant was 12.7 days (range, 5-26), and in 5 cases we placed a biliary drainage (Kehr tube) during surgery. Primary graft nonfunction did not occur after LT in this cohort, although, we registered one case of biliary anastomosis stricture that was managed endoscopically by endoscopic retrograde cholangiopancreatography. All patients are alive and none required retransplantation. CONCLUSIONS: In our experience with controlled DCD donors, the demonstration of: (1) a negative trend of lactate during normothermic regional perfusion; (2) an aspartate aminotransferase and alanine aminotransferase level lower than 2000 mU/dL; and (3) less than 1 hour of functional warm ischemia time along with no signs of microscopic or macroscopic ischemia of the grafts, are related to positive outcomes in the first year after transplant. A DCD risk score based on Italian population characteristics and regulations on death observation may improve donor-recipient match and avoid futile transplants.

Robotic liver resection for hepatocellular carcinoma: A systematic review.

BACKGROUND: Hepatocellular carcinoma (HCC) represents a leading cause of death in patients with cirrhosis. This review attempts to clarify the role of robotic surgery for HCC in terms of oncologic outcomes. MATERIALS AND METHODS: A systematic literature search was performed according to the PRISMA statement including papers comparing open, robotic, and laparoscopic approach for liver surgery. If more than one study was reported by the same institute, only the most recent or the highest quality study was included. RESULTS: The literature search yielded 302 articles; titles and abstracts were reviewed for inclusion. Ten papers were finally included in this review for a total of 307 patients who underwent robotic resection for HCC. CONCLUSIONS: Robotic liver resection for HCC is effective in terms of oncological results as compared with open and laparoscopic approach when performed in experienced centers and is accurate in terms of R0 rates and disease-free surgical margin.

Vacuum-assisted management of surgical site infections after liver transplantation: 15-year experience in a tertiary hepatobiliary center.

Immune compromised as well as critically ill patients are at higher risk of surgical wound infection and dehiscence. Wound infections critically influence the outcomes after liver transplantation. In particular, it was shown that they significantly reduce the overall survival rate when compared to patients with uneventful wound healing, and their occurrence is associated with death or graft loss within 1-year post-transplantation. From January 2001 through December 2017, 763 patients underwent liver transplantation in our Institution, the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, "Policlinico" University Hospital, University of Modena and Reggio Emilia, Modena, Italy. We retrospectively analyzed data from our prospectively maintained database of patients treated with a negative pressure therapy device due to wound or abdominal infections. 13 patients underwent negative pressure treatments for surgical site infection after liver transplantation in our institution. Ten superficial "supra-fascial" applications (SF group) and three deeper abdominal (Ab group) were reported. Mean in-hospital stay for the SF group was 42.6 days, ranging from 8 to 80, while for the Ab group was 62 days (range 23-133), with an overall survival of 34 and 4.6 months, respectively. A multifactorial multidisciplinary approach is needed in the prevention of surgical site infections instead of mere antimicrobial prophylaxis The application of negative pressure wound therapy may help in controlling the diffusion of the infection and preventing sepsis.

Extra-Anatomic Jump Graft from the Right Colic Vein: A Novel Technique to Manage Portal Vein Thrombosis in Liver Transplantation.

BACKGROUND: In the context of cirrhosis, portal vein thrombosis (PVT) is present in 2.1% to 26% of patients. PVT is no longer considered an absolute contraindication for liver transplantation, and nowadays, surgical strategies depend on the extent of PVT. Complete PVT is associated with higher morbidity rates and poor prognosis, while comparable long-term outcomes can be achieved as long as physiological portal inflow is restored. MATERIALS AND METHODS: We report our experience with a 45-year-old patient undergoing liver transplant with a PVT (stage III-b). To restore portal vein inflow to the liver, an extra-anatomic jump graft from the right colic vein with donor iliac vein interposition was constructed. RESULTS: The patient recovered well, with a progressive improvement of the general conditions, and was finally discharged on p.o.d. 14. No anastomotic defects were found at the postoperative CT scan 10 months after the surgery. CONCLUSION: Our technical innovation represents a valid and safe alternative to the cavoportal hemitransposition, providing a proper flow restoration and reproducing a physiological setting, while avoiding the complications related to the cavoportal shunt. We believe that the reconstitution of liver portal inflow should be obtained with the most physiological approach possible and considering long-term liver function.

Laparoscopic versus robotic surgery for hepatocellular carcinoma: the first 46 consecutive cases.

BACKGROUND: Hepatocellular carcinoma has a growing incidence worldwide, and represents a leading cause of death in patients with cirrhosis. Nowadays, minimally invasive approaches are spreading in every field of surgery and in liver surgery as well. MATERIALS AND METHODS: We retrospectively reviewed demographics, clinical, and pathologic characteristics and short-term outcomes of patients who had undergone minimally invasive resections for hepatocellular carcinoma at our institution between June 2012 and May 2016. RESULTS: No significant differences in demographics and comorbidities were found between patients in the laparoscopic (n = 24) and robotic (n = 22) groups, except for the rates of cirrhotic patients (91.7% and 68.2%, respectively, P = 0.046). Perioperative data analysis showed that the operative time (mean, 211 and 318 min, respectively, P < 0.001) was the only parameter in favor of laparoscopy. Conversely, robotic-assisted resections were related to less Clavien I-II postoperative complications (22 cases versus 13 cases; P = 0.03). As regards resection margins, the two groups were similar with no statistically significant differences in rates of disease-free resection margins. CONCLUSIONS: A modern hepatobiliary center should offer both open and minimally invasive approaches to liver disease to provide the best care for each patient, according to the individual comorbidities, risk factors, and personal quality of life expectations. Our results show that the robotic approach is a reliable tool for accurate oncologic surgery, comparable to the laparoscopic approach. Robotic surgery also allows the surgeon to safely approach liver segments that are difficult to resect in laparoscopy, namely segments I-VII-VIII.