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J Santoyo

Publications and source records attributed to J Santoyo.

At least 19 recordsLinked to original sources

True impact of the indication of cirrhosis and the MELD on the results of liver transplantation.

UNLABELLED: Our Aim was to determine the impact of cirrhosis and the preoperative MELD score on the immediate postoperative mortality and hospital stay as well as survival at 1, 5, and 8 years in liver transplantation. MATERIALS AND METHODS: Transplanted cirrhotic patients were selected who did not display some of the main known risk factors affecting recipient. Donor and surgical technique were included in this analysis. These exclusion criteria for recipient factors were emergency transplants and retransplants; for donor factors, age over 60 years, ischemia time over 10 hours, and moderate or severe steatosis on back-bench biopsy; and for surgery, prior complex upper abdominal surgery (mainly derivative and gastroduodenal surgery). Among 340 total liver transplants including 16 retransplants performed from March 1997 to December 2005, 197 patients met the selection criteria. The mean age of the recipients was 52 years (17-67) and the donors, 39 years (11-60). The transplant indication was cirrhosis in all cases: HCV in 69 cases (35%); alcohol in 55 (28%); hepatocarcinoma in 38 (19%); HBV in 19 (10%); PBC in 8 (4%), and other etiologies in 8 cases (4%). The MELD scores were divided as group 1, <10 points (33 cases = 17%); group 2, 10 to 18 points (136 cases = 69%); and group 3, >18 points (28 cases = 14%). The statistical analysis was performed with SPSS 11.0. RESULTS: Postoperative mortality (up to 3 months) was 16 cases (8%). The median ICU and hospital stays were 3 and 13.5 days, respectively. Overall survivals at 1, 5, and 8 years were 89%, 80%, and 77%, respectively. The survival for the same periods according to MELD group was 97%, 97%, and 97% for group 1; 87%, 76%, and 72% for group 2; and 85%, 81%, and 81% for group 3 (P = NS). The survival according to the three main indications at 1, 5, and 8 years was: HCV, 91%, 80%, and 80%; alcohol, 87%, 80%, and 71%; and hepatocarcinoma, 84%, 80%, and 80% (P = NS). No significant differences were observed among early deaths between MELD groups or transplant indications. CONCLUSIONS: In a favorable liver transplant setting including acceptable donors, absence of prior complex abdominal surgery in the recipient, and nonemergency transplants, neither the cause of the cirrhosis nor its severity, as measured preoperatively by the MELD, were predictive of early postoperative death or long-term survival.

Adolescent↗

Transfusion requirements during liver transplantation: impact of a temporary portacaval shunt.

UNLABELLED: We evaluated the consumption of blood products during liver transplantation in cirrhotic patients association with the placement of a temporary portacaval shunt (TPCS). PATIENTS AND METHODS: We retrospectively divided 349 cirrhotic patients transplanted in our unit between March 1997 and October 2005 into two groups: transplants without a TPCS (group I, 189 cases) and those with a TPCS (group II, 160 cases). In all cases, we preserved the inferior vena cava (piggyback). The dependent variables were consumption of blood-derived products (banked red cells, recovered red cells, fresh frozen plasma, platelets), surgery time, kidney function, intensive care unit stay, and hospital stay. RESULTS: Consumption of blood products was significantly lower among patients who received a TPCS. In group II, no platelet transfusion was required in 54% of the patients, and no banked red cells in 12% compared with 18% and 3%, respectively, among group I patients (P < .005). The mean overall transplant procedure time was 74 minutes shorter in group II (361 minutes) compared with group I (435 minutes) (P < .001). The overall hospital stay was shorter among patients transplanted after TPCS. CONCLUSION: Liver transplantation with a TPCS was accompanied by a reduction in the intraoperative use of blood-derived products, especially platelet transfusion. Among other advantages, this reduction resulted in a shorter posttransplant hospital stay.

Blood Component Transfusion↗

Influence of degree of hepatic steatosis on graft function and postoperative complications of liver transplantation.

The aim of this study was to evaluate the impact on initial graft function of the degree of steatosis detected in the back-table biopsy, and its repercussion on the clinical results of the transplant (early posttransplant mortality and morbidity). We undertook a retrospective analysis of 300 liver transplants performed at our center from 1997 to 2004. A wedge liver biopsy was done routinely during back-table surgery (available in 294 transplants). The degree of steatosis was classified as: S0-no steatosis, 201 transplants; S1-mild steatosis (<30%), 58 transplants; S2-moderate steatosis (30% to 60%), 18 transplants; and S3-severe steatosis (>60%), 17 transplants. The ischemia-reperfusion (I/R) injury, based on the maximum mean peak aspartate transferase in the first 72 posttransplant hours, tended to be greater as the degree of graft steatosis increased: S0, 1316; S1, 1985; S2, 2446; and S3, 2955 (P < .005 between S0 and S3). This greater initial hepatic dysfunction was correlated in the group with severe steatosis with a higher rate of severe renal failure requiring hemofiltration/hemodialysis: S0, 9%; S1, 15%; S2, 11%; and S3, 41% (P < .001); as well as with a higher early mortality (90 days): S0, 10%; S1, 21%; S2, 11%; and S3, 41% (P < .001). The Kaplan-Meier survival curve showed a significant difference (log-rank and Breslow) between the group with severe steatosis and the group with no steatosis (P = .002). We conclude that the degree of liver graft steatosis is an important determinant of I/R injury, although this progressive increase in the I/R injury with the degree of steatosis only had clinical repercussions in the case of severe steatosis.

Fatty Liver↗

Preoperative factors and models predicting mortality in liver transplantation.

We analyzed preoperative factors related to postoperative mortality after liver transplantation among a cohort of 268 consecutive liver transplant patients over 6 years. We studied the impact of 10 recipient variables, 14 donor features, and three operative aspects. We also studied the correlation with death and survival using various predictive scores (Child, Cordoba Score, MELD, and UCLA). Univariate analysis showed that the factors with a significant association with postoperative mortality were the use of noradrenaline in the donor, total ischemia time (>12 hours), and transplant indication (hepatitis C virus versus the rest). Multivariate analysis of mortality showed the impact of female donor sex, recipients over >60 years, recipient albumin less than 2.8, and total graft ischemia time more than 12 hours. Univariate analysis of 1-year survival showed a statistically significant relation with D/R gender similarity, as well as donor GOT (>170) and GPT (>140) values. Multivariate analysis of 1-year survival showed donor GOT (>170) and donor/recipient gender similarity to be significant. Concerning the prediction models, Child-Pugh (AB versus C) best determined postoperative mortality (P < .006), MELD was predictive of 1-year survival (P < .03). The most important variables related to postoperative mortality were total ischemia time over 12 hours, recipient albumin less than 2.8, and age above 60 years. The variable with most impact on 1-year survival was the degree of graft hepatocyte lesion as determined by GOT. The Child-Pugh system is still the best indicator of postoperative mortality, although MELD may also be a good predictor of survival.

Age Factors↗

Liver transplant results for hepatocellular carcinoma applying strict preoperative selection criteria.

INTRODUCTION: Liver transplantation is currently the best therapeutic option for small hepatocellular carcinoma (HC) in selected cirrhotic patients. The main aim of this study was to analyze the results of a recent series of liver transplant cirrhotic patients with small HC applying strict preoperative selection criteria. PATIENTS AND METHODS: During a period of 6 years we performed 53 liver transplants with a final diagnosis of HC on cirrhosis. The selection criteria for liver transplantation (LT) by modern imaging techniques were the Milan criteria (TNM I and II of the modified classification). RESULTS: Of the 53 patients, 44 (83%) were transplanted with preoperatively known HC, and 9 (17%) with incidental HC. The mean time on the waiting list was 74 +/- 62 days. Despite using strict selection criteria, 23 patients (43%) exceeded the Milan criteria in the specimen and 17 (32%) even exceeded the extended criteria of the UCSF. With a mean follow-up of 2 years, only two patients have developed recurrences. The overall survival at 1, 3, and 5 years was 80%, 70%, and 70%, respectively. The survival of patients that exceeded the Milan or USF criteria at 1, 3, and 5 years was 72% and 76%; 67% and 69%; 67% and 69%, respectively. CONCLUSIONS: The results of liver transplantation for HC are excellent when applying strict preoperative selection criteria. The current imaging methods lead to a considerable infrastaging percentage (30% to 40%), extending the indications for liver transplant due to HC beyond the scope that clinical reports would justify.

Carcinoma, Hepatocellular↗

Liver transplantation for hilar cholangiocarcinoma: Spanish experience.

INTRODUCTION: Palliative treatment for nondisseminated irresectable hilar cholangiocarcinoma (HCC) carries a 0% 5-year survival rate. The role of orthotopic liver transplantation (OLT) in these patients is controversial because the survival rate is lower than that for other indications for transplantation and the lack of available donor organs. The aim of this paper was to review the Spanish experience in OLT for HCC and identify prognostic factors for survival. METHODS: We retrospectively reviewed 36 patients undergoing OLT for HCC over 13 years. RESULTS: The actuarial survival rate at 1, 3, and 5 years was 82%, 53%, and 30%, respectively. The main cause of death was tumor recurrence (53%). In the univariate analysis, the factors for a poor prognosis were vascular invasion (P<.001) namely 0% survival at 3 years when present versus 63% and 35% at 3 and 5 years, respectively, when it was not; and stages III to IVA (P<.05), namely 15% survival at 5 years versus 47% for stages I to II. Lymph node and perineural invasion also reduce survival. In the multivariate analysis, the factors for poor prognosis included vascular invasion (P<.01) and stages III to IVA (P<.01). CONCLUSION: OLT for nondisseminated irresectable HCC has higher survival rates at 3 and 5 years than palliative treatments, especially with initial stage tumors, which means that more information is needed to better select cholangiocarcinoma patients for transplantation.

Bile Duct Neoplasms↗

Liver transplantation for peripheral cholangiocarcinoma: Spanish experience.

INTRODUCTION: Palliative treatment for nondisseminated unresectable peripheral cholangiocarcinoma (PCC) carries a 0% 5-year survival rate. The role of orthotopic liver transplantation (OLT) in these patients is controversial because the survival rate is lower than with other indications for transplantation and the lack of available donor organs. The aim of this paper was to review the Spanish experience in OLT for PCC to identify prognostic factors for survival. METHODS: We retrospectively reviewed 23 patients undergoing OLT in Spain for PCC over a period of 13 years. RESULTS: The actuarial survival rates were 77%, 65%, and 42% at 1, 3, and 5 years, respectively. The main cause of death was tumor recurrence (35%). Prognotic factors for an adverse outcome were pTNM classification (P<.05) in the univariate analysis and perineural invasion (P<.05) and stages III or IVA (P<.05) in the multivariate analysis. CONCLUSIONS: OLT for nondisseminated irresectable PCC displays higher survival rates at 3 and 5 years than palliative treatments, especially for tumors in the initial stages, which means that more information is needed to help better select PCC patients for transplantation.

Bile Duct Neoplasms↗

Selection criteria for liver transplantation in early-stage hepatocellular carcinoma with cirrhosis: results of a multicenter study.

Orthotopic liver transplantation (OLT) offers the only chance to eliminate both tumor and liver disease in patients with hepatocellular carcinoma (HCC) and cirrhosis. However, tumor progression while on the waiting list and recurrence after OLT are frequent. We undertook a large multicenter study to assess survival and related factors of recurrence after OLT. This retrospective study analyses data from 307 consecutive patients with HCC and cirrhosis treated with OLT between 1990 and 1997 in eight centers in Spain. OLT was indicated only for small (<5 cm) localized tumors. Five-year rates after OLT were 63% for survival, 58% for disease-free survival, and 21% for recurrence. Tumor diameter larger than 5 cm was associated with other tumor characteristics that were significant indicators of poor outcome (absence of capsule, three or more nodules, bilobularity, satellite nodules, and vascular invasion). However, in multivariate analysis, alpha fetoprotein (AFP) levels greater than 300 ng/mL (P = .04; P = .02) and macroscopic vascular invasion (P = .01; P = .0001) were the only factors independently associated with mortality and recurrence, respectively. OLT is indicated in patients with small HCCs who have low AFP levels and no macroscopic vascular invasion or extrahepatic disease. By increasing our ability for preoperative tumor imaging, we will achieve better selection of patients with HCC before OLT.

Adult↗

Use of the breast implant for liver graft malposition.

Transplantation of a small liver into a large patient may cause problems with correct reperfusion of the graft because of torsion of the hepatic pedicle, leading to malfunction of the transplanted organ. We describe the case of a 60-year-old man with alcoholic cirrhosis and hepatitis B virus who received a small-sized liver graft. Owing to the lack of adequate reperfusion of the transplanted organ arising from pedicular kinking caused by disparate sizes, a breast implant was placed behind the graft as a means of support, thereby resolving the problem. The use of prosthetic materials for the correct placement of grafts with size incongruity is also discussed, and the literature is reviewed.

Breast Implants↗

Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2alpha kinase.

In eukaryotic cells, protein synthesis is regulated in response to various environmental stresses by phosphorylating the alpha subunit of the eukaryotic initiation factor 2 (eIF2alpha). Three different eIF2alpha kinases have been identified in mammalian cells, the heme-regulated inhibitor (HRI), the interferon-inducible RNA-dependent kinase (PKR) and the endoplasmic reticulum-resident kinase (PERK). A fourth eIF2alpha kinase, termed GCN2, was previously characterized from Saccharomyces cerevisiae, Drosophila melanogaster and Neurospora crassa. Here we describe the cloning of a mouse GCN2 cDNA (MGCN2), which represents the first mammalian GCN2 homolog. MGCN2 has a conserved motif, N-terminal to the kinase subdomain V, and a large insert of 139 amino acids located between subdomains IV and V that are characteristic of the known eIF2alpha kinases. Furthermore, MGCN2 contains a class II aminoacyl-tRNA synthetase domain and a degenerate kinase segment, downstream and upstream of the eIF2alpha kinase domain, respectively, and both are singular features of GCN2 protein kinases. MGCN2 mRNA is expressed as a single message of approximately 5.5 kb in a wide range of different tissues, with the highest levels in the liver and the brain. Specific polyclonal anti-(MGCN2) immunoprecipitated an eIF2alpha kinase activity and recognized a 190 kDa phosphoprotein in Western blots from either mouse liver or MGCN2-transfected 293 cell extracts. Interestingly, serum starvation increased eIF2alpha phosphorylation in MGCN2-transfected human 293T cells. This finding provides evidence that GCN2 is the unique eIF2alpha kinase present in all eukaryotes from yeast to mammals and underscores the role of MGCN2 kinase in translational control and its potential physiological significance.

Amino Acid Sequence↗

[Hepatocellular carcinoma associated to porphyria cutanea tarda and hepatitis C virus infection without cirrhosis].

The molecular basis of porphyria cutanea tarda is defective activity of hepatic uroporphyrinogen decarboxylase. A common characteristic is liver dysfunction than goes from cirrhosis to hepatocellular carcinoma. A high prevalence of hepatitis C virus markers has been demonstrated. We study a patient with PCT and hepatitis C virus markers that finally develops to hepatocellular carcinoma without previous cirrhosis. Previous studies with association of PCT and hepatitis C virus markers, have found liver diseases ranging from cirrhosis to hepatocellular carcinoma. The importance of this study is the absence of cirrhosis.

Carcinoma, Hepatocellular↗

Cloning and characterization of a cDNA encoding a protein synthesis initiation factor-2alpha (eIF-2alpha) kinase from Drosophila melanogaster. Homology To yeast GCN2 protein kinase.

Phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF-2alpha) is one of the best-characterized mechanisms for downregulating protein synthesis in mammalian cells in response to various stress conditions. In Drosophila, such a regulatory mechanism has not been elucidated. We report the molecular cloning and characterization of DGCN2, a Drosophila eIF-2alpha kinase related to yeast GCN2 protein kinase. DGCN2 contains all of the 12 catalytic subdomains characteristic of eukaryotic Ser/Thr protein kinases and the conserved sequence of eIF-2alpha kinases in subdomain V. A large insert of 94 amino acids, which is characteristic of eIF-2alpha kinases, is also present between subdomains IV and V. It is particularly notable that DGCN2 possesses an amino acid sequence related to class II aminoacyl-tRNA synthetases, a unique feature of yeast GCN2 protein kinase. DGCN2 expression is developmentally regulated. During embryogenesis, DGCN2 mRNA is dynamically expressed in several tissues. Interestingly, at later stages this expression becomes restricted to a few cells of the central nervous system. Affinity-purified antibodies, raised against a synthetic peptide based on the predicted DGCN2 sequence, specifically immunoprecipitated an eIF-2alpha kinase activity and recognized an approximately 175 kDa phosphoprotein in Western blots of Drosophila embryo extracts.

Amino Acid Sequence↗

Localization, structure and expression of the gene for translation initiation factor eIF-4E from Drosophila melanogaster.

Drosophila melanogaster contains a single copy of the gene encoding translation eukaryotic initiation factor eIF-4E, which maps in the 67A2B1 region of chromosome 3L. A genomic clone containing the entire eIF-4E gene was isolated and sequenced. Comparison of this sequence with a cDNA previously obtained in our laboratory and 5'-RACE analysis revealed the existence of three mRNAs that are generated by alternative splicing of a primary transcript. All of them have different 5' untranslated leader regions. Two of the mRNAs encode the same eIF-4E polypeptide, whose sequence has been deduced from the cDNA clone. The third mRNA species contains a new open reading frame, possibly encoding another isoform of eIF-4E, which is very similar in size to the other but has a different N-terminal sequence. Several sequences which may be involved in the regulation of transcription initiation of the eIF-4E gene, except for a consensus TATA box, were found upstream of the putative transcription initiation sites. Expression of the eIF-4E gene is spatially and temporally controlled during embryonic development. It is ubiquitously expressed during embryogenesis but transcripts preferentially accumulate in certain tissues, particularly in the pole cells, at different developmental stages.

Alternative Splicing↗

The eIF-2alpha kinases and the control of protein synthesis.

Protein synthesis is regulated in response to environmental stimuli by covalent modification, primarily phosphorylation, of components of the translational machinery. Phosphorylation of the alpha subunit of eIF-2 is one of the best-characterized mechanisms for down-regulating protein synthesis in higher eukaryotes in response to various stress conditions. Three distinct protein kinases regulate protein synthesis in eukaryotic cells by phosphorylating the alpha subunit of eIF-2 at serine-51. There are two mammalian eIF-2alpha kinases: the double-stranded RNA-dependent kinase (PKR) and heme-regulated inhibitor kinase (HRI), and the yeast GCN2. The regulatory mechanisms and the molecular sizes of these eIF-2alpha kinases are different. The expression of PKR is induced by interferon, and the kinase activity is stimulated by low concentrations of double-stranded RNA. HRI is activated under heme-deficient conditions. Yeast GCN2 is activated by amino acid starvation. The phosphorylation of eIF-2alpha results in the shutdown of protein synthesis. Nevertheless, the eIF-2alpha kinases can regulate both global as well as specific mRNA translation. Inhibition of protein synthesis correlates with eIF-2alpha phosphorylation in response to a wide variety of different stimuli, including heat shock, serum deprivation, glucose starvation, amino acid starvation, exposure to heavy metal ions, and viral infection. Finally, recent studies suggest a role for eIF-2alpha phosphorylation in the control of cell growth and differentiation.

Amino Acid Sequence↗

[Shunt surgery versus disconnection in portal hypertension. A comparative study].

Controversy remains about the best treatment for patients with esophagogastric variceal bleeding. In spite of different therapeutic alternatives and recent progress, such as liver transplantation of TIPS, many patients will finally be treated by standard surgery. With the aim to know the results of surgery in shunting vs non-shunting procedures, we have analyzed a recent and consecutive series of 68 cirrhotics patients operated on for variceal hemorrhage. According to the surgical technique there were three groups: I) 30 patients underwent a total portacaval shunt; II) 18 cases with an azygosportal disconnection; III) 20 patients with a partial portacaval shunt (8-10 mm H-portacaval PTFE graft). All groups were homogeneous considering age, sex etiology, Child-Pugh grade and timing of surgery (elective vs urgent). The complications and mortality rates were similar for the three groups. The overall operative mortality was 10%, and 5% in selected cases (Child-Pugh A-B, non urgent cases). With a follow-up for I, II and III group of 47, 44 and 27 months respectively, chronic encephalopathy have been seen in 61%, 15% and 15% respectively (p < .05). No patient in group I has rebled, and only one case in the II and III groups had a recurrence of hemorrhage. The actuarial three years survival was 76%, 86% and 85% (p NS), and the five year survival was 41% vs 86% for the groups I and II respectively (p < .05). In conclusion, in selected cases, surgery gives excellent immediate and long term results. In patients with variceal bleeding and failure of first line treatments, such as sclerosis or pharmacology, the partial H-portacaval shunt and non-shunting procedures are good alternatives, with low incidence of rebleeding and chronic encephalopathy.

Adult↗

Long esophagoplasty: functional study.

The functional results of different types of plasty were evaluated in 46 patients who had undergone esophageal replacement for different pathologies. The patients were classified into three groups according to the type of plasty: I) 19 ileocecocolonoplasties (ICC), II) 11 left colonoplasties (LC), III) 16 gastroplasties (GP). The postoperative studies made were: a) clinical evaluation, b) radiological barium contrast study, c) isotopic transit of semisolid food marked with 99m-Tc colloidal sulfur and d) manometry. The clinical evaluation disclosed no significant differences between the three groups. Isotopic scans revealed more rapid emptying of the ICC, with elimination by the ileal segment in the first minute of 76.3 +/- 3.3% of the isotope, and by the entire plasty of 79.4 +/- 4.2% in 15 minutes (p less than 0.001). The manometric study showed non-response by the GP. The motor activity of the terminal ileoplasty was greater than that of the other plasties studied, and that of the right colonoplasty was greater than that of the left (p less than 0.01). Likewise, the clearance of acid (HCl 0.1N) by the ICC was more rapid than that of the LC (p less than 0.01). It is concluded that, functionally, the ICC is a better long esophagoplasty than the other procedures studied.

Adult↗