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.

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.

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.

Increase in survival of liver grafts after rinsing with warm Ringer's solution due to improvement of hepatic microcirculation.

Temperature increases membrane fluidity and decreases vascular resistance in isolated organs. Therefore, these studies were designed to determine if a rinse with warm buffer could increase survival time in the rat model of orthotopic liver transplantation by improving hepatic microcirculation. Brief periods of warm ischemia (3-8 min) did not damage the liver as indexed by minimal release of LDH. Survival of rats for 30 days was greater than 90% in this model when livers were stored for 1 hr in Ringer's solution; yet grafts stored for 8 hr in Euro-Collins solution and rinsed with 20 ml of cold (0-4 degrees C) Ringer's solution survived postoperatively only around 3 days. However, livers stored for 8 hr in Euro-Collins and rinsed with 20 ml of warm (37 degrees C) Ringer's survived longer than 30 days (i.e., permanently). Serum transaminase levels reached peak values around 6000 U/L one day postoperatively in the cold-rinsed group, and liver injury assessed histologically was substantial. Under these conditions, pulmonary infiltration of inflammatory cells was observed in about 23% of lung tissue examined and was associated with massive bleeding. Following a warm rinse, however, maximal SGOT levels and injury to both liver and lung were reduced significantly by 80-90% 24 hr postoperatively. Moreover, the warm rinse improved hepatic microcirculation. It accelerated blood flow into the liver approximately two-fold, as indexed by the half-time of changes in hemoglobin reflectance from the liver surface, improved the distribution of colloidal carbon in the organ observed macroscopically, and decreased vascular resistance by over 50%. These data support the hypothesis that a brief rinse of liver grafts with warm buffer markedly improves the hepatic microcirculation, leading to dramatic improvement in graft survival. This work demonstrates clearly that a brief warm rinse may be useful clinically in liver transplantation.

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.

[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.

[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.

[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.

[Value of percutaneous ethanol injection in the treatment of hepatocellular carcinoma in a cirrhotic liver]. / Intérêt de l'alcoolisation percutanée dans le traitement du carcinome hépatocellulaire sur foie cirrhotique.

Percutaneous ethanol injection treatment, introduced ten years ago as palliative therapy for patients with inoperable hepatocellular carcinoma, can now be used with a curative intent to treat small tumours with results comparable to surgical resection. This progress, made possible by sophisticated radiological techniques, makes percutaneous ethanol injection the treatment of choice for patients with poor liver function in whom resection is not possible and local control of the disease is desirable either for prolonged palliation or in view of liver transplantation. For patients with large tumours, or in case of recurrence after previous surgical treatment, a therapeutic approach combining transarterial lipiodol chemoembolisation and percutaneous ethanol injection has shown promising results and deserves further investigation.

[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.

[Combined liver and small intestine transplantation in an adult. First case in France. Medical aspects: digestive and nutritional]. / Transplantation combinée foie-intestin grêle chez l'adulte.

OBJECTIVE: We report the digestive, hepatic, intestinal and nutritional history of the first combined liver-small bowel transplantation performed in France in an adult recipient. Currently, the clinical course has been favorable at 30 months. METHODS: In May 1997, a 21-year-old man underwent a double liver-small bowel transplantation for irreversible chronic bowel failure with severe chronic liver disease subsequent to post-surgical short-bowel syndrome. After 28 laparotomies, there were 15 cm of small bowel left for the gastric anastomosis. The patient had a terminal jejunostomy and a left colostomy, excluding a short segment of the transverse colon and the rectum. Total parenteral nutrition including lipids and been initiated in December 1992 (3500 kcal/d) and had led to severe complications. Intestinal absorption before and after the graft were studied with the balance method (input-output) and used bomb calorimetry and measurements of the steatorhhea and creatorrhea. Functional enterocyte mass was assessed from serum citrullin. RESULTS: The postoperative period after the liver-bowel graft (220 cm small bowel with terminal ileostomy and jejunostomy) was uneventful. The immunosuppression protocol included tacrolimus, corticosteroids and azathioprin. One mild episode of acute rejection occurred at day 26 and was controlled with a corticosteroid bolus. No episode of liver rejection occurred. Moderate renal failure regressed partially after reestablishing the fluid-electrolyte balance and adapting tacrolimus dosage. Total parenteral nutrition which had sustained the patient for 4 and a half years was definitely discontinued three months after transplantation. Oral nutrition was initially associated with enteral nutrition (from day 20 to day 90) and became exclusive three months after the transplantation. Intestinal absorption coefficients measured before tranplantation, at 3 months (2200 kcal/d, ileostomy flow 1600 g/d), and at 18 months (2400 kcal/d, ileostomy flow 1300 g/d) post transplantation were, respectively, 22%, 90% and 88% for overall calorie absorption, 25%, 65% and 73% for fat absorption, and 47%, 83% and 67% for nitrogen absorption. At 18 months post-graft, there was a spectacular improvement in the patient's neurological status and his liver function was normal. Endoscopy, radiography, histology, and immunohistochemistry explorations were normal. Ileo-rectal anastomosis was re-established at 23 months post-transplantation. At 30 months the patient is living in his home and on 100% oral nutrition. CONCLUSION: Clinical, nutritional and functional outcome at 30 months in this first French case of liver-small bowel transplantation in an adult recipient has been excellent.

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.

Stimulation of monooxygenation and conjugation after liver transplantation in the rat: involvement of Kupffer cells.

The success rate of liver transplantation has improved markedly during the last few years and, although this patient population receives multiple drug therapies, the effect of liver transplantation on drug metabolism has been studied very little. Therefore, the purpose of this study was to assess the metabolism of model drug substrates after liver transplantation in the rat. Rat livers were stored for 4 hr in cold Euro-Collins solution, transplanted orthotopically, and then perfused 2 hr later with oxygenated Krebs-Henseleit buffer, using a nonrecirculating system. Rates of monooxygenation of the model compound p-nitroanisole, conjugation of p-nitrophenol, and uptake of oxygen were measured. All parameters studied were elevated significantly, by nearly 2-fold, by transplantation. Specifically, monooxygenation was increased from 2.9 +/- 0.2 to 5.1 +/- 0.4 mumol/g/hr, conjugation was elevated from 3.3 +/- 0.6 to 7.7 +/- 0.1 mumol/g/hr, and O2 uptake was stimulated from basal values of 114 to 197 mumol/g/hr. Transplantation did not, however, alter rates of monooxygenation and conjugation in isolated microsomes supplemented with excess cofactor. When donor rats were pretreated with the Kupffer cell toxicant gadolinium chloride (10 mg/kg, intravenously) 30 hr before liver storage, the elevation after transplantation in all parameters studied was prevented. Depletion of carbohydrate reserves by fasting of donor rats did not prevent stimulation of monooxygenation and conjugation. On the other hand, urea synthesis from ammonium chloride, a process dependent on mitochondrial NADPH, was increased and monooxygenation was diminished after transplantation, suggesting the involvement of mitochondria in this phenomenon. Indeed, mitochondria isolated 2 hr postoperatively exhibited significantly elevated respiratory control ratios and higher state 3 rates of respiration. Taken together, these data support the hypothesis that Kupffer cells, activated by transplantation, release mediators that stimulate mitochondria in parenchymal cells and enhance drug metabolism by increasing cofactor supply (e.g., NADPH for monooxygenation and UDP-glucuronic acid for glucuronidation).