José Fuster

Intrahepatic biliary lesions after orthotopic liver transplantation

Abstract Intrahepatic biliary lesions (IBL) are rare (2–9 %) after orthotopic liver transplantation (OLT). The aim was to evaluate the incidence, etiology and outcome. In nine years, a total 532 OLTs were performed in 481 patients. Twenty-four patients developed IBL. Eight were due to HAT, seven to ABOI, three to CDR and six to PI. The time until diagnosis of HAT is longest in patients (14 ± 6) with IBL. ABOI is another cause of IBL. CDR is a rare cause of IBL, however when it takes place, patients must undergo Rtx. Finally, PI is a relevant cause of IBL. In order to suppress the incidence of IBL we should consider 1) the systematic use of Doppler-Ultrasound; 2) emergency reoperation of patients with HAT, 3) avoid ABOI in OLT; 4) Rtx in cases of CDR, and 5) OLT should still be performed as an emergency procedure.

Lack of effect of metoclopramide and domperidone on esophageal peristalsis and esophageal acid clearance in reflux esophagitis: A randomized, double-blind study

The acute effects of oral metoclopramide (40 mg/day) and domperidone (80 mg/day) on esophageal motor activity and acid reflux were assessed in a randomized, double-blind, placebo-controlled study in 20 patients with erosive reflux esophagitis. Esophageal motor function was assessed by standard manometry with wet swallows, and reflux events were evaluated by ambulatory 24-hr pH-monitoring. Both drugs caused a significant (P<0.05) increase in lower esophageal sphincter pressure lasting at least 120 min. However, neither esophageal body motility, duration of esophageal exposure to acid, nor esophageal clearance were effected by drug administration in comparison to placebo. Side effects were reported in two patients who received metoclopramide, while no adverse effects occurred after domperidone intake. In conclusion, the so-called motility agents metoclopramide and domperidone have few acute effects on esophageal motility in patients with erosive reflux esophagitis.

Decompression of the portal bed and twice-baseline portal inflow are necessary for the functional recovery of a "small-for-size" graft.

Background.In partial liver transplant, a reduction in the intrahepatic vascular bed produces a rise in the portal vein flow and the portal venous pressure gradient, leading to endothelial and, thereby, hepatocellular injury and death in a process known as “small-for-size” (SFS) syndrome. Objective.To demonstrate that a calibrated portocaval shunt prevents superfluous inflow in a porcine model of SFS transplant. Methods.Donor pigs (15–20 kg) underwent 70% hepatectomy. In 2 groups, a 6 mm (S6) (n = 6) or 12 mm (S12) (n = 6) Gore-Tex shunt was placed between the portal vein and infrahepatic inferior vena cava. In a third group, no portocaval shunt was placed (SFS) (n = 17). Grafts were stored for 5 hours at 4°C and then transplanted into recipients (30–35 kg). Results.Five-day survival was 29% in SFS, 100% in S6, and 0 in S12. Postreperfusion portal vein flow was 4-, 2-, and 1-times flow at baseline in SFS, S6, and S12, respectively. With respect to portal venous pressure gradient, both the 6- and 12-mm shunts effectively decompressed the portal bed. Aspartate aminotransferase and bilirubin rose and the Quick prothrombin time fell in all animals after reperfusion but improved significantly by day 5 in S6. Serum levels of endothelin-1 remained elevated in SFS and S12 but returned to baseline by 12 hours in S6: 2.76 (2.05–4.08) and 2.04 (1.97–2.12) versus 0.43 (0.26–0.50) pg/mL, respectively (P < 0.05 for both comparisons). Conclusions.A calibrated portocaval shunt that maintains portal vein flow about twice its baseline value produces a favorable outcome after SFS liver transplantation, avoiding endothelial injury due to portal hyperperfusion or to hypoperfusion because of excess shunting.

Prostacyclin, thromboxane and oxygen free radicals and postoperative liver function in human liver transplantation

The aim of this prospective study is to evaluate prostanoid (prostacyclin and thromboxane) and lipid peroxide levels at the portal and hepatic veins, and their relation to immediate postoperative liver function. Nineteen patients with liver cirrhosis undergoing orthotopic liver transplantation were prospectively studied. Blood samples were obtained within 5 min and 1 and 2 hr after reperfusion of the new liver, through a catheter placed at the portal vein in the recipient and another at the left hepatic vein in the donor liver. Plasma prostacyclin and thromboxane were analyzed by HPLC and RIA. The formation of lipid peroxides was determined and expressed in terms of thiobarbituric acid-reacting substances. Immediate postoperative liver function was evaluated using the transaminase levels within the first 48 hr and the early postoperative graft function score, as described previously. After reperfusion, only determinations at 5 min were related with liver function. Either prostacyclin (R = -0.61, P = 0.004) levels at the hepatic vein or prostacyclin production (subtraction between hepatic and portal vein levels) (R = -0.47, P = 0.04) correlated significantly with the early postoperative graft function score. Besides, there was a significant relationship between lipid peroxide production as measured by thiobarbituric acid-reacting substances and a worse early postoperative graft function score (R = 0.61, P = .005). These results suggest that prostacyclin released after liver grafting attenuates preservation and reperfusion damage of the liver, supporting the hypothesis that there is an imbalance of prostanoids within the microvasculature in patients with a compromised postoperative liver function. Our results agree with the involvement of some degree of lipid peroxidation products in the damage of hepatocytes during anoxia and reperfusion.

Importance of the Temporary Portocaval Shunt During Adult Living Donor Liver Transplantation

Adult living donor liver transplantation (aLDLT) is associated with surgical risks for the donor and with the possibility of small‐for‐size syndrome (SFSS) for the recipient, with both events being of great importance. An excessively small liver graft entails a relative increase in the portal blood flow during reperfusion, and this factor predisposes the recipient to an increased risk of SFSS in the postoperative period, although other causes related to recipient, graft, and technical factors have also been reported. A hemodynamic monitoring protocol was used for 45 consecutive aLDLT recipients. After various hemodynamic parameters before reperfusion were analyzed, a significant correlation between the temporary portocaval shunt flow during the anhepatic phase and the portal vein flow (PVF) after reperfusion of the graft (R2 = 0.3, P < 0.001) was found, and so was a correlation between the native liver portal pressure and PVF after reperfusion (R2 = 0.21, P = 0.007). The identification of patients at risk for excessive portal hyperflow will allow its modulation before reperfusion. This could favor the use of smaller grafts and ultimately lead to a reduction in donor complications because it would allow more limited hepatectomies to be performed. Liver Transpl 19:174–183, 2013.

Step-by-step guide for a simplified model of porcine orthotopic liver transplant.

BACKGROUND Based on similar anatomy, physiology, and size to humans, pigs provide an excellent means for studying new therapies related to orthotopic liver transplant (OLT). Techniques that have been described to date, however, are unnecessarily complex and increase the likelihood of morbidity and adverse outcome. MATERIALS AND METHODS Male outbred weanling pigs underwent OLT according to our procedure, with a short anhepatic time (<20 min) and without veno-venous bypass or vasoactive substances during the anhepatic phase. Vascular anastomoses were performed identical to the clinical setting, and a simple stented choledochocholedochostomy was created. RESULTS The authors have performed this procedure 130 times using four transplant models: standard, whole-liver (n = 10), small-for-size (n = 48), donor after cardiac death (n = 44), and donor adenoviral gene transfection (n = 28). The average cold ischemic and anhepatic times were 302 ± 43 and 17 ± 3 min, respectively. Hypotension was successfully treated with intravenous fluids. In all cases, the recipient survived the operation and was extubated. Survival to the end follow-up varied according to the model and was 56% (73/130) for all cases. At autopsy or euthanasia, no vascular thrombosis or outflow obstruction was found. Survival was 100% for pigs transplanted with standard, whole-liver grafts (n = 10). In this group, AST and bilirubin rose during the first 24 h after graft reperfusion, while the Quick prothrombin time (QPT) fell. By the fifth postoperative day, these parameters had returned to baseline. CONCLUSIONS This model is straightforward and reproducible and offers surgeons and researchers the opportunity to perform OLT studies under clinically relevant conditions.

TAG-72, CA 19.9 AND CEA AS TUMOR MARKERS IN GASTRIC CANCER

Serum levels of CEA, CA 19.9 and TAG-72 were measured in 79 patients with active gastric cancer, 47 with treated gastric cancer and no clinical evidence of the disease and 33 with benign gastric disease. In the patients with active gastric cancer TAG-72 was increased in 47%, CA 19.9 in 46% and CEA in 33%. The sensitivity of these markers was related to the stage of the disease, although upon comparison of stages I-II and III-IV significant difference was observed only for TAG-72. The combined use of two of the markers increased the sensitivity compared with the use of only one. The results suggest that the combination of TAG-72 and CA 19.9 may be useful in the post surgical management of patients with gastric cancer.

Chediak-Higashi syndrome: description of two novel homozygous missense mutations causing divergent clinical phenotype

Chediak–Higashi syndrome (CHS) is a rare autosomal recessive disease resulting from mutations in the LYST/CHS1 gene, which encodes for a 429 kDa protein, CHS1/LYST, that regulates vesicle trafficking and determines the size of lysosomes and other organelles. To date, 60 different mutations have been characterized, and a reasonably straightforward phenotype–genotype correlation has been suggested. We describe two patients on opposite ends of the CHS clinical spectrum with novel missense mutations. We characterized these patients in terms of their mutations, protein localization and expression, mRNA stability, and electrostatic potential. Patient 1 is the first report of a severe early‐onset CHS with a homozygous missense mutation (c.11362 G>A, p.G3725R) in the LYST/CHS1 gene. This molecular change results in a reduction at the CHS1 protein level, not due to an mRNA effect, but maybe a consequence of both, a change in the structure of the protein and most likely attributable to the remarkable serious perturbation in the electrostatic potential. Patient 2, who exhibited the adolescence form of the disease, was found to be homozygous for a novel missense mutation c.961 T>C, p.C258R, which seemed to have minor effect on the structure of the CHS1/LYST protein. Reexamining accepted premises of missense mutant alleles being reported among patients with clinically mild forms of the disorder should be carried out, and attempts to link genotype and clinical phenotype require identifying the actual molecular effect of the mutation. Early and accurate diagnosis of the severity of the disease is extremely important to early differentiate patients who would benefit from premature enrollment into a transplantation protocol.

Time-related improvement of survival in resectable gastric cancer: the role of Japanese-style gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy

BackgroundWe investigated the change of prognosis in resected gastric cancer (RGC) patients and the role of radical surgery and adjuvant chemotherapy.MethodsWe retrospectively analyze the outcome of 426 consecutive patients from 1975 to 2002, divided into 2 time-periods (TP) cohort: Before 1990 (TP1, n = 207) and 1990 or after (TP2; n= 219). Partial gastrectomy and D1-lymphadenetomy was predominant in TP1 and total gastrectomy with D2-lymphadenectomy it was in TP2. Adjuvant chemotherapy consisted of mitomycin C (MMC), 10–20 mg/m2 iv 4 courses or MMC plus Tegafur 500 mg/m2 for 6 months.ResultsPositive nodes were similar in TP2/TP1 patients with 56%/59% respectively. Total gastrectomy was done in 56%/45% of TP2/TP1 respectively. Two-drug adjuvant chemotherapy was administered in 65%/18% of TP2/TP1 respectively. Survival at 5 years was 66% for TP2 versus 42% for TP1 patients (p < 0.0001). Survival by stages II, IIIA y IIIB for TP2 versus TP1 patients was 70 vs. 51% (p = 0.0132); 57 vs. 22% (p = 0.0008) y 30 vs. 15% (p = 0.2315) respectively. Multivariate analysis showed that age, stage of disease and period of treatment were independent variables.ConclusionThe global prognosis and that of some stages have improved in recent years with case RGC patients treated with surgery and adjuvant chemotherapy.

Lack of correlation between preoperative and intraoperative liver hemodynamics: a descriptive analysis.

Background Adult living-donor liver transplantation recipients undergo important hemodynamic changes during the procedure, which in turn have proven to be of the upmost importance when dealing with small grafts, to avoid the so-called “small-for-size” syndrome. Methods Back in 2003, we started a hemodynamic monitoring protocol in adult living-donor liver transplantation recipients, which evaluated the hemodynamic status of the patient 24 hr before, during, and 3 days after transplantation. We analyzed the correlation between the same hemodynamic variables measured in the hemodynamic laboratory and those taken in the operating room. Results With the exception of cardiac index and indexed systemic vascular resistance, all the other hepatic and systemic hemodynamic parameters measured before and during the intervention, as well as during and after the intervention, showed a lack of correlation. Conclusion The observed lack of correlation may happen due to many factors, such as the influence of vasoactive and anesthetic drugs, total muscular relaxation, or the presence of an open abdomen. As a result, a direct comparison between hemodynamic values should only be done when measured in the same conditions.