Influence of 4 preservation solutions on ICU stay, graft and patient survival following liver transplantation.

OBJECTIVE: The goal of this study was to evaluate the prognostic role of four preservation solutions in liver transplantation (LT). PATIENTS AND METHODS: This is a retrospective study originating from 22 French centers performing LT, registered in the prospective databank of the Cristal Biomedicine Agency between 2008 and 2013. The preservation solutions used were Celsior (CS), Institut Georges Lopez (IGL)-1, Solution de Conservation des Organes et des Tissus (SCOT) 15 and University of Wisconsin (UW) solutions. Exclusion criteria were preservation with unknown or inhomogeneous solutions, or Histidine-tryptophan-ketoglutarate (HTK) solution (representing only 3% of LT). Patient survival was the main endpoint. Secondary endpoints were graft survival and duration of stay in intensive care. RESULTS: Of 6347 LT performed, 4928 were included in this study, for which the distribution of preservation solution was CS (30%), IGL-1 (44%), SCOT 15 (10%) and UW (16%). Patient survival was 86%, 80% and 74% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.78). Graft survival was 82%, 75% and 69% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.80). Duration of intensive care was different according to the solution used in univariate analysis (P<0.001), but this effect disappeared in multivariate analysis when the center performing the transplantation was accounted for. CONCLUSION: The type of preservation solution used (CS, IGL-1, SCOT 15 or UW) did not have any influence on patient or graft survival after LT.

Impact of graft preservation solutions for liver transplantation on early cytokine release and postoperative organ dysfunctions. A pilot study.

INTRODUCTION: During liver transplantation, graft ischemia-reperfusion injury leads to a systemic inflammatory response producing postoperative organ dysfunctions. The aim of this observational and prospective study was to compare the impact of Solution de conservation des organes et tissus (SCOT) 15 and University of Wisconsin (UW) preservation solutions on early cytokine release, postreperfusion syndrome and postoperative organ dysfunctions. METHODS: Thirty-seven liver transplantations were included: 21 in UW Group and 16 in SCOT 15 group. Five cytokines were measured in systemic blood after anesthetic induction, 30minutes after unclamping portal vein and on postoperative day 1. RESULTS: Following unclamping portal vein, cytokines were released in systemic circulation. Systemic cytokine concentrations were higher in UW than in SCOT 15 group: Interleukin-10, Interleukine-6. In SCOT 15 group, significant reduction of postreperfusion syndrome incidence and acute kidney injury were observed. Alanine and aspartate aminotransferase peak concentrations were higher in SCOT 15 group than in UW group. However, from postoperative day 1 to day 10, aminotransferase returned to normal values and did not differ between groups. CONCLUSIONS: Compared to UW, SCOT 15 decreases systemic cytokine release resulting from graft ischemia-reperfusion injury and reduces incidence of postreperfusion syndrome and postoperative renal failure.

French survey of the first three-years of liver transplantation activity from uncontrolled donors deceased after cardiac death.

OBJECTIVE: To assess the first three years of French activity related to liver transplantation from uncontrolled donation after cardiac death (uDCD). STUDY DESIGN: Prospective and observational study in the three active centres authorized by the French Biomedicine Agency. PATIENTS AND METHODS: All patients deceased between 2010 and 2012 after an uncontrolled cardiac arrest admitted to one of three centres (Pitié-Salpêtrière, Saint-Louis or Bicêtre hospitals, AP-HP, Paris, France) and potentially eligible for liver recovery were included. Abdominal normothermic oxygenated recirculation (ANOR) was used for graft preservation. RESULTS: One hundred twenty-six potential uDCD donors were identified as eligible for liver recovery after hospital admission. The main causes of organ recovery failure were technical failure related to ANOR (29 patients, 23%), refusal of consent (39 patients, 31% of potential uDCD donors and 40% of asked relatives) and abnormal hepatic transaminases up to 200 UI.L(-1) during ANOR (24 patients, 19%). Finally, 11 livers were transplanted. Process efficiency was 9% [95% CI: 4-15%]. One-year recipient survival was 82%, [95% CI: 48-98%] and one-year graft survival was 64% [95% CI: 31-89%]. CONCLUSION: Liver transplantation from uDCD donors is achievable in France, despite low process efficiency.

Liver preservation with SCOT 15 solution decreases posttransplantation cholestasis compared with University of Wisconsin solution: a retrospective study.

BACKGROUND: SCOT 15 is a new solution to preserve abdominal organs for transplantation. Its principal characteristic is the use of polyethylene glycol. Herein We report our experience using SCOT 15 compared with the reference University of Wisconsin (UW) solution for hepatic transplantation. METHODS: We compared 2 groups: SCOT 15 (n = 33; 2009-2010) versus UW (n = 34; 2008-2010), which were paired for cold and warm ischemic times, donor ages, and graft weights. Endpoints were biologic tests in the first 2 months after the operation. A linear mixed model was used to evaluate longitudinal changes and influences of each solution. RESULTS: No primary failure was observed. At postoperative day 0, transaminase values were higher in the SCOT 15 than in the UW group: aspartate transaminase: 2,435 ± 399 vs 589 ± 83 IU/L (P < .01); alanine transaminase: ALT: 1,207 ± 191 vs 484 ± 64 IU/L (P < .05), then returned to low levels in both groups. From day 0 to 8, coagulation factors reached normal values; there was no difference between the 2 groups. Total bilirubin decreased similarly in the 2 groups. However, from the second postoperative week (W1) to W8, the SCOT 15 group showed a slow decrease in the mean values of gamma-glutamyltranspeptidase (gGT) from 233 ± 125 to 130 ± 161 IU/L, which were significantly lower than those in the UW group, where the gGT remained around 300 IU/L (P < .01). The End-Stage Liver Disease, Child-Pugh, or United Network for Organ Sharing scores, primary liver diseases, hepatitic C virus status, arterial or biliary complications, and male/female ratio, which was different in the 2 groups, did not statistically influence these results. CONCLUSIONS: The main effect of cold storage of human liver using SCOT 15 compared with UW solution was to decrease cholestasis following transplantation.

Sonographic preoperative assessment of liver volume before major liver resection.

OBJECTIVE: The use of ultrasonography is widespread for both the diagnosis and treatment of liver tumors. However, the measurement of liver volume by ultrasonography is not commonly done. We report an original method of liver volumetry using ultrasonography and an investigation into the usefulness of ultrasonography in this context. METHODS: The data for 50 patients undergoing various types of major hepatectomy were collected. We preoperatively measured liver volume using ultrasonography, dividing the liver into three main compartments according to precise anatomical landmarks, and then made comparisons with the volume of the actual specimen after hepatectomy, for all of the study participants. RESULTS: Total volume correlation between the two groups was good (r = 0.916, P < 0.001). However, the correlation was weaker in cases of right hepatectomy compared with other types of hepatectomy. CONCLUSION: This study demonstrates the possibility of doing liver volumetry using an ultrasound device. Further investigation to establish the reliability of this easily available and noninvasive approach is needed.

Laparoscopic liver resection of benign liver tumors.

OBJECTIVE: The objective of this study was to assess the feasibility, safety, and outcome of laparoscopic liver resection for benign liver tumors in a multicenter setting. BACKGROUND: Despite restrictive, tailored indications for resection in benign liver tumors, an increasing number of articles have been published concerning laparoscopic liver resection of these tumors. METHODS: A retrospective study was performed in 18 surgical centres in Europe regarding their experience with laparoscopic resection of benign liver tumors. Detailed standardized questionnaires were used that focused on patient's characteristics, clinical data, type and characteristics of the tumor, technical details of the operation, and early and late clinical outcome. RESULTS: From March 1992 to September 2000, 87 patients suffering from benign liver tumor were included in this study: 48 patients with focal nodular hyperplasia (55%), 17 patients with liver cell adenoma (21%), 13 patients with hemangioma (15%), 3 patients with hamartoma (3%), 3 patients with hydatid liver cysts (3%), 2 patients with adult polycystic liver disease (APLD) (2%), and 1 patient with liver cystadenoma (1%). The mean size of the tumor was 6 cm, and 95% of the tumors were located in the left liver lobe or in the anterior segments of the right liver. Liver procedures included 38 wedge resections, 25 segmentectomies, 21 bisegmentectomies (including 20 left lateral segmentectomies), and 3 major hepatectomies. There were 9 conversions to an open approach (10%) due to bleeding in 45% of the patients. Five patients (6%) received autologous blood transfusion. There was no postoperative mortality, and the postoperative complication rate was low (5%). The mean postoperative hospital stay was 5 days (range, 2-13 days). At a mean follow-up of 13 months (median, 10 months; range, 2-58 months), all patients are alive without disease recurrence, except for the 2 patients with APLD. CONCLUSIONS: Laparoscopic resection of benign liver tumors is feasible and safe for selected patients with small tumors located in the left lateral segments or in the anterior segments of the right liver. Despite the use of a laparoscopic approach, selective indications for resection of benign liver tumors should remain unchanged. When performed by expert liver and laparoscopic surgeons in selected patients and tumors, laparoscopic resection of benign liver tumor is a promising technique.

Exacerbation of oxaliplatin neurosensory toxicity following surgery.

Combination of chemotherapy and surgical resection of metastases is the most promising strategy to improve the fraction of long-term survivors and cured patients in metastatic colorectal cancer. We reproducibly observed evidence of exacerbation of the oxaliplatin-induced neurosensory toxicity following surgery. Total, protein-bound and intra-erythrocytic concentrations of oxaliplatin were measured, whenever possible, immediately prior to surgery and 4, 24 and 48 h following surgical resection. Among 12 patients, seven (58%) patients reported immediate post-operative aggravation of the pre-existing neurotoxicity. At the time of surgery, we detected high intra-erythrocytic platinum concentrations in all patients (median: 1365 micro g/l, range: 820-2968 micro g/l). While ultrafilterable oxaliplatin was not detectable prior to surgery, it could be detected immediately after surgery and during 48 h. These results suggest that patients heavily pretreated with oxaliplatin may experience aggravation of neurotoxicity after surgery, probably through a redistribution of the pool of intra-erythrocytic oxaliplatin biotransformation products into the plasma. This clinical observation might be the consequence of peroperative hemolysis.

Auxiliary partial orthotopic versus standard orthotopic whole liver transplantation for acute liver failure: a reappraisal from a single center by a case-control study.

OBJECTIVE: To reappraise the results of auxiliary partial orthotopic liver transplantation (APOLT) compared with those of standard whole-liver transplantation (OLT) in terms of postoperative death and complications, including neurologic sequelae. SUMMARY BACKGROUND DATA: Compared with OLT, APOLT preserves the possibility for the native liver to recover, and to stop immunosuppression. METHODS: In a consecutive series of 49 patients transplanted for fulminant or subfulminant hepatitis, 37 received OLT and 12 received APOLT. APOLT was done when logistics allowed simultaneous performance of graft preparation and the native liver partial hepatectomy to revascularize the graft as soon as possible. Each patient undergoing APOLT (12 patients) was matched to two patients undergoing OLT (24 patients) according to age, grade of coma, etiology, and fulminant or subfulminant type of hepatitis. All grafts in the study population were retrieved from optimal donors. RESULTS: Before surgery, both groups were comparable in all aspects. In-hospital death occurred in 4 of 12 patients undergoing APOLT compared with 6 of 24 patients undergoing OLT. Patients receiving APOLT had 1 +/- 1.3 technical complications compared with 0.3 +/- 0.5 for OLT patients. Bacteriemia was significantly more frequent after APOLT than after OLT. The need for retransplantation was significantly higher in the APOLT patients (3/12 vs. 0/24). Brain death from brain edema or neurologic sequelae was significantly more frequent after APOLT (4/12 vs. 2/24). One-year patient survival was comparable in both groups (66% vs. 66%), and there was a trend toward lower 1-year retransplantation-free survival rates in the APOLT group (39% vs. 66%). Only 2 of 12 (17%) patients had full success with APOLT (i.e., patient survival, liver regeneration, withdrawal of immunosuppression, and graft removal). One of these two patients had neurologic sequelae. CONCLUSIONS: Using optimal grafts, APOLT and OLT have similar patient survival rates. However, the complication rate is higher with APOLT. On an intent-to-treat basis, the efficacy of the APOLT procedure is low. This analysis suggests that the indications for an APOLT procedure should be reconsidered in the light of the risks of technical complications and neurologic sequelae.

[Adult to adult living-related liver transplantation. The Paul-Brousse Hospital preliminary experience]. / Transplantation hépatique de l'adulte à partir de donneur vivant.

AIM: Liver-graft shortages justify the development of adult living-related liver transplantation. The preliminary experience with this technique at Paul-Brousse Hospital is reported. PATIENTS ET METHODES: From January to July 2000, 7 adult to adult living-related liver transplantations were performed. Donors were 5 females and 2 males aged 20 to 53 years old (median: 41). A right liver graft was harvested in all cases. Recipients were 5 males and 2 females aged from 17 to 58 years old (median: 50) transplanted for viral cirrhosis (4 cases including 2 with hepatocellular carcinoma), subfulminant hepatitis (1 case), hepatocellular carcinoma on a healthy liver (1 case), and epithelioid hemangioendothelioma (1 case). Follow-up ranged from 41 to 157 days (median: 117 days). RESULTS: One donor had a biliary fistula that healed spontaneously. One donor had asterixis for 24 hours. The 7 donors are alive at home without any late complications. One recipient was retransplanted for hepatic artery thrombosis and 2 recipients had a biliary fistula that healed spontaneously. The 7 recipients are alive at home with normal liver function. CONCLUSION: Our experience and other reports suggest that adult to adult living-related liver transplantation is feasible with rare mortality and low morbidity in donors. Results in recipients are comparable to those obtained with cadaveric grafts. For a given patient the possibility of living related donation might extend the indications for transplantation without penalizing patients waiting for a cadaveric graft.

[Multistage liver resections in colorectal liver metastases. The Paul Brousse concept]. / Mehrzeitige Leberresektionen bei colorectalen Lebermetastasen. Das Paul Brousse-Konzept.

Hepatic resection is currently the only form of treatment that offers a chance of long-term survival, with rates ranging from 25% to 39%. However, a curative operation can be performed in only 10% of patients with colorectal metastases to the liver. Our policy is to increase the number of patients that can benefit from liver resection. Liver metastases can be considered as irresectable mainly in three different situations (sometimes associated): (I) large and/or poorly located tumors; (II) bilateral tumors in both liver lobes; (III) tumors technically resectable, but not operable because the liver remnant is too small, which is associated with a prohibitive risk of postoperative severe liver failure. The aim of this paper is to report the strategies we use in our center to achieve curative resection in these three schematic situations despite initial contraindications.

Split-liver transplantation for two adult recipients: feasibility and long-term outcomes.

OBJECTIVE: To identify the outcomes and risks of split-liver transplantation (SLT) for two adult recipients to determine the feasibility of more widespread use of this procedure to increase the graft pool for adults. SUMMARY BACKGROUND DATA: The shortage of cadaver liver grafts for adults is increasing. Using livers from donors defined as optimal, the authors have been developing techniques for SLT for two adult recipients at their center. METHODS: From July 1993 to December 1999, 34 adults have undergone SLT with grafts from optimal donors prepared by ex situ split (n = 30) or in situ split (n = 4), and 88 adults received optimal whole-liver grafts that were not split. Four split-grafts were transplanted at other centers. The outcomes of transplantation with right and left split-liver grafts were compared with those of whole-liver transplants. The main end points were patient and graft survival at 1 and 2 years and the incidence and types of complications. RESULTS: For whole-liver, right and left split-liver grafts, respectively, patient survival rates were 88%, 74%, and 88% at 1 year and 85%, 74%, and 64% at 2 years. Graft survival rates were 88%, 74%, and 75% at 1 year and 85%, 74%, and 43% at 2 years. Patient survival was adversely affected by graft steatosis and recipients inpatient status before transplantation. Graft survival was adversely affected by steatosis and a graft-to-recipient body weight ratio of less than 1%. Primary nonfunction occurred in three left split-liver grafts. The rates of arterial (6%) and biliary (22%) complications were similar to published data from conventional transplantation for an adult and a child. SLT for two adults increased the number of recipients by 62% compared with whole-liver transplantation and was logistically possible in 16 of the 104 (15%) optimal cadaver donors. CONCLUSIONS: Split-liver transplantation for two adults is technically feasible. Outcomes and complication rates can be improved by rigid selection criteria for donors and recipients, particularly for the smaller left graft, and possibly also by in situ splitting in cadaver donors. Wider use will require changes in the procedures for graft allocation and coordination between centers experienced in the techniques.

[Chemotherapy by isolated liver perfusion with endovascular occlusion catheter: preliminary experience in pigs]. / Chimiothérapie par perfusion isolée du foie avec clampage cave endovasculaire: expériences préliminaires chez le porc.

UNLABELLED: Very high concentrations of cytotoxic drug may be obtained with chemotherapy performed with vascular exclusion. OBJECTIVE: To study the pharmacokinetics and toxicity of melphalan during in situ isolated liver perfusion, and to test an endovascular occlusion catheter. METHODS: Isolated liver perfusion with melphalan (15 mg bolus) was performed in 6 pigs (50-60 kg) for 30 min, with non-oxygenated Ringer's solution. Hepatic outflow, collected by a double balloon catheter inserted into the retrohepatic inferior vena cava, was pumped into the gastroduodenal artery, while the common hepatic artery and portal vein were clamped. RESULTS: A maximum concentration of 30,000 ng/mL was obtained in the circuit before an exponential decrease, while the concentration in systemic blood was less than 500 ng/mL (n = 3). Before closing the abdomen, melphalan concentrations were about 2,000 ng/mg in the liver, and undetectable in the muscle. Postoperative course (2 weeks, n = 2) was uneventful with minor alterations in blood tests and hepatic histology. CONCLUSION: This method of local chemotherapy with melphalan appears to be safe with minor leakage and minimal toxicity.

[Use of a water-jet dissector during hepatectomy]. / Utilisation d'un dissecteur à jet d'eau au cours des hépatectomies.

STUDY AIM: A new water jet cutting system was used by an hepatobiliary surgical team for hepatectomy in ten patients. The aim of this retrospective study was to assess advantages and disadvantages of this new apparatus for liver dissection. MATERIAL AND METHOD: This procedure uses the mechanical power of water jet under pressure in the liver incision. The study concerned feasibility of the hepatectomy, the ease of use of the apparatus and volume of the blood loss. RESULTS: The water jet was very easy to use and of maintenance (bag of sterile saline in a non sterile pressurized container, disposable handpiece). Any liver resection could be performed using this tool, independently of the liver consistency. There was no decrease in the duration of surgery and the blood loss compared to the ultrasonic cutting system. Minor splashing, bubbles and mist impaired the accuracy of the vascular dissection. CONCLUSION: The water jet dissector used in this series is a simple, economic and useful tool to perform liver resection.

Paul Brousse Liver Transplantation: the first 1,500 cases.

During the past 16 years, more than 1,500 liver transplants were performed at Paul Brousse Hospital. The overall patient survival rates were 83% at one year and 65% at 10 years. Our group has pioneered a variety of new approaches to liver transplantation, including: 1. Anti-HBs (HBIG) prophylaxis for the prevention of HBV recurrence. To date more than 270 patients have received long-term treatment and the overall 10-year recurrence rate was 27%. 2. Transplantation for hepatocellular carcinoma of the cirrhotic liver in patients with uni- or binodular HCC (< 3 cm). Survival for transplanted patients was 83% compared with 18% if the liver was resected. 3. Transplantation for familial amyloidotic polyneuropathy (FAP). More than 60 patients had 5- and 10-year survival rates of 85% and 83%, respectively. Ten livers obtained after hepatectomy from these FAP patients were transplanted as "domino" living donor livers to patients with unresectable liver cancers with satisfactory short-term results. 4. Reduced-size liver grafts have been used successfully to reduce pretransplant mortality and posttransplant morbidity and mortality by shortening the wait for our pediatric patients. 5. Split-liver transplantation has increased the number of transplantable livers by 28%. 6. Split-liver transplantation for 2 adults. Using optimal livers we have transplanted 34 adults with grafts prepared by ex-vivo or in-situ splitting with good survival rates. 7. Adult-to-adult living-related donor liver transplantation. In 2000, 7 adult-to-adult living donor transplants were performed with no complications from the donor surgeries. One recipient was retransplanted for arterial thrombosis, but all 7 recipients are alive at home. The Paul Brousse Hospital is committed to exploring new technologies to improve the outcome of and expand the indications for liver transplantation. We have taken a surgical approach to the organ shortage, finding new ways to serve the most patients with the limited number of livers available.

[Combined transplantation of liver and small intestine in an adult. First case in France. Surgical aspects]. / Transplantation combinée foie-intenstin grêle chez l'adulte.Premier cas français. Aspects chirurgicaux.

BACKGROUND: We report hare the first adult case of combined liver-small bowel transplantation performed in France. CASE REPORT: A double liver + small bowel graft was transplanted in a 21-year-old patient hospitalized for 4 years for a short bowel syndrome requiring total parenteral nutrition. The patient also had severe hepatic fibrosis. The immediate post-operative period was uneventful. Two and one-half years after the double graft, the patient is on strictly oral nutrition, no longer has a stomy and lives a normal life in his home. DISCUSSION: The advent of tacrolimus has led to long-term success of bowel grafts, developed earlier in children and now possible in adults. Combined liver-small bowel transplantation is formally indicated in patients with cirrhogenic liver disease associated with ineversible small bowel failure.