Exploratory analysis of clinical benefit of ipilimumab and nivolumab treatment in patients with metastatic melanoma from a single institution.

PURPOSE: We retrospectively analysed overall survival (OS) and potential predictive biomarkers of OS in patients with metastatic melanoma treated with ipilimumab plus nivolumab in a single institution. METHODS AND PATIENTS: Electronic medical records of patients with advanced melanoma receiving ≥ 1 dose of a combined ipilimumab plus nivolumab regimen between March 3, 2016 and March 7, 2020 in a single institution, were reviewed. OS was analysed using the Kaplan-Meier method. Sub-group analyses were conducted to examine several endpoints according to relevant clinical, molecular and pathological variables using logistic and Cox models. RESULTS: Forty-four cases were reviewed, 38 (86.4%), of whom had cutaneous melanoma, 21 (47.7%) were BRAF mutant, 21 (47.7%) presented high lactate dehydrogenase (LDH) values, 23 (52.3%) had ≥ 3 disease sites, and 10 (22.7%) patients had brain metastases. The median follow-up was 37.7 months, and the median OS was 21.1 months (95% CI 8.2-NR). In the multivariate analysis, the OS was significantly longer in patients with an Eastern Cooperative Oncology Group (ECOG) score of 0, LDH ≤ upper limit of normal, absence of liver metastases and neutrophil-to-lymphocyte ratio (NLR) < 5 (all p ≤ 0.05, log-rank test). These factors allowed the classification of patients into three prognostic risk groups (low/intermediate/high risk) for death. CONCLUSION: Overall survival of real-world patients from our cohort receiving ipilimumab plus nivolumab was lower than in previous studies. The ECOG score, LDH values, the presence of liver metastases and the NLR were independent prognostic factors for survival.

Factors Associated with Prolonged Recipient Hepatectomy Time During Liver Transplantation: A Single-Centre Experience.

BACKGROUND: Recipient hepatectomy during liver transplantation can be a challenging operation and can increase cold ischaemic time. The aim of this study is to assess factors associated with prolonged recipient hepatectomy. METHODS: From 2005 to 2015, 930 patients were submitted to liver transplantation in our hospital. Prolonged hepatectomy time was defined as operative time >180 min (from knife on skin to total hepatectomy). Patients undergoing early liver retransplantation and living donation were excluded. RESULTS: A total of 715 patients were included in our study. Median age at transplantation was 53 (18-70) years, and median BMI was 26.2 (16-40). Median hepatectomy time was 131 min. Prolonged hepatectomy time occurred in 89 (12.4%) patients. At univariate analysis, previous decompensated cirrhosis with variceal bleeding and/or ascites, higher BMI and previous abdominal surgery were associated with prolonged operating time. Higher surgeon experience and acute liver failure were associated with shorter hepatectomy time. At multivariate analysis, previous episodes of variceal bleeding (p = 0.027, OR 1.78), BMI > 27 (p = 0.01, OR 1.75), previous abdominal surgery (p = 0.04, OR 1.68) and surgeon experience (p = 0.007, OR 2.04) were independently associated with operating time. Prolonged hepatectomy time was significantly associated with cold and total ischaemic time and intraoperative bleeding (p < 0.001, p = 0.002 and p = 0.002, respectively). CONCLUSIONS: Recipient BMI, previous episodes of variceal bleeding, previous abdominal surgery and surgeon experience are independently associated with hepatectomy duration. These factors can be helpful to identify those patients with potentially prolonged hepatectomy time, and therefore, strategies can be put in place to optimize outcomes in this group of patients.

Perfusión aislada de extremidad inferior con fuga de quimioterapéutico / Isolated limb perfusion with cytostatic drug leakage

La perfusión aislada de la extremidad es el tratamiento del melanoma en estadio iii, con metástasis en tránsito. Esta técnica permite la administración de citostáticos a concentración y temperatura eficaces, que no podrían ser administrados de manera sistémica debido a su toxicidad. La toxicidad debido al paso a la circulación sistémica de quimioterápico procedente de la extremidad es la complicación más grave a corto plazo, y se manifiesta mediante el síndrome de respuesta inflamatoria sistémica en el postoperatorio inmediato. La detección precoz de esta complicación y su manejo perioperatorio requiere un abordaje multidiscilplicar, en el que el anestesiólogo tiene un papel clave. Presentamos un caso de perfusión aislada de la extremidad inferior en el que el procedimiento tuvo que ser interrumpido por paso de factor de necrosis tumoral a la circulación sistémica, con grave repercusión hemodinámica intraoperatoria (AU)

Isolated limb perfusion is the treatment of stage III melanoma with in-transit metastasis. This technique allows the administration of cytostatics at an effective concentration and temperature, which could not be administered systemically because of their toxicity. The toxicity due to leakage of the chemotherapy agent from the limb into the systemic circulation is the most serious short-term complication, and is manifested by a systemic inflammatory response syndrome in the immediate post-intervention period. Early detection of this complication and its peri-operative management requires a multidisciplinary approach, in which the anaesthesiologist plays a key role. A case of isolated lower limb perfusion is reported in which the procedure had to be interrupted due to the passage of tumour necrosis factor into the systemic circulation, with severe intra-operative haemodynamic repercussions (AU)

Isolated limb perfusion with cytostatic drug leakage. / Perfusión aislada de extremidad inferior con fuga de quimioterapéutico.

Isolated limb perfusion is the treatment of stage III melanoma with in-transit metastasis. This technique allows the administration of cytostatics at an effective concentration and temperature, which could not be administered systemically because of their toxicity. The toxicity due to leakage of the chemotherapy agent from the limb into the systemic circulation is the most serious short-term complication, and is manifested by a systemic inflammatory response syndrome in the immediate post-intervention period. Early detection of this complication and its peri-operative management requires a multidisciplinary approach, in which the anaesthesiologist plays a key role. A case of isolated lower limb perfusion is reported in which the procedure had to be interrupted due to the passage of tumour necrosis factor into the systemic circulation, with severe intra-operative haemodynamic repercussions.

Successful Pancreas Transplantation From a Deceased Donor Intoxicated With Oral Antidiabetic Agent: A Case Report.

Simultaneous kidney pancreas transplantation (SKP) is a common procedure for the patient with long-term type 1 diabetes mellitus (DM) with terminal renal failure. It is unusual to consider the pancreas from a deceased donor who died after an acute intoxication with oral antidiabetic agent (OAA), which would suggest an abnormal functionality of the organ and preclude the potential use of the graft. We present a case of a successful pancreatic transplantation from a donor who died of acute cerebral edema secondary to severe hypoglycemia induced by OAA acute intoxication.

Electroquimioterapia en metástasis cutáneas de melanoma: experiencia en 31 casos / Electrochemotherapy in the treatment of melanoma skin metastases: a report on 31 cases

INTRODUCCIÓN Y OBJETIVOS: la electroquimioterapia (EQT) es una técnica terapéutica indicada en tumores cutáneos y subcutáneos no resecables quirúrgicamente. La EQT se fundamenta en la acción sinérgica de un fármaco antineoplásico junto con la electroporación de las membranas celulares para aumentar su citotoxicidad. El objetivo del presente estudio es objetivar la eficacia clínica, así como el perfil de seguridad de la EQT como tratamiento en pacientes con recidivas o metástasis cutáneas locorregionales de melanoma no abordables quirúrgicamente. MATERIAL Y MÉTODOS: Entre enero de 2007 y diciembre de 2012 se incluyeron 31 pacientes. Todos los tratamientos se realizaron siguiendo las guías de consenso European Standard Operating Procedures of Electrochemotherapy (ESOPE). La respuesta se calculó por paciente, obteniendo la media del conjunto de las lesiones. RESULTADOS: En el 49% de los casos se demostró una respuesta parcial y en el 23% se obtuvo una respuesta completa. Diecisiete pacientes mantuvieron la respuesta al año de seguimiento. En el 28% existió progresión de la enfermedad. Las complicaciones locales inmediatas (dolor, edema, eritema) fueron leves, y se resolvieron en las primeras 48 h en la mayoría de los casos. Ocho pacientes presentaron complicaciones locales posteriores, como ulceración y sobreinfección, secundarias a la necrosis de las lesiones y fueron controladas con tratamientos tópicos. CONCLUSIONES: La EQT presenta un excelente perfil de eficacia, eficiencia y seguridad, siendo de gran utilidad en el control de la enfermedad locorregional avanzada en el melanoma en lesiones no resecables quirúrgicamente

INTRODUCTION AND OBJECTIVES: electrochemotherapy is indicated for the treatment of unresectable cutaneous and subcutaneous tumors. The technique involves the synergistic use of electroporation of cell membranes to increase the cytotoxicity of anticancer drugs delivered to the tumor cells. The aim of this study was to analyze the clinical effectiveness and safety of electrochemotherapy in the treatment of unresectable locoregional recurrent or metastatic melanomas. MATERIAL AND METHODS: We studied 31 patients treated between January 2007 and December 2012. The European Standard Operating Procedures of Electrochemotherapy (ESOPE) were applied in all cases. Treatment response was analyzed as overall patient response (mean response based on results for all lesions treated in a given patient). RESULTS: Response was classified as partial in 49% of patients and complete in 23%. At 1 year, the level of response achieved had been maintained in 17 patients. Disease progression was observed in 28% of the series. Immediate local complications (pain, swelling, erythema) were mild and resolved within 48 hours in most cases. Eight patients developed subsequent local complications, such as ulcers and secondary infections associated with necrosis of the lesions. These complications were brought under control with topical treatments. CONCLUSIONS: Electrochemotherapy is a very effective, safe, and efficient treatment for advanced locoregional disease in patients with unresectable melanoma lesions

Dermoscopy structures as predictors of sentinel lymph node positivity in cutaneous melanoma.

BACKGROUND: Histological features such as Breslow thickness, ulceration and mitosis are the main criteria to guide sentinel lymph node biopsy (SLNB) in melanoma. Dermoscopy may add complementary information to these criteria. OBJECTIVES: To evaluate the correlation between dermoscopy structures and SLNB positivity. METHODS: Retrospective analysis of 123 consecutive melanomas with Breslow thickness > 0·75 mm, SLNB performed during follow-up and dermoscopic images. RESULTS: Men were more likely to have a positive SLNB. The presence of ulceration and blotch and the absence of a pigmented network in dermoscopy correlated with positive SLNB. Histological ulceration also correlated with positive SLNB. A dermoscopy SCORE predicted SLN status with a sensitivity of 96·3% and a specificity of 30·2%. When sex and Breslow thickness were added (SCOREBRESEX), the sensitivity remained at 96·3% but the specificity increased to 52·1%. This study is limited by the number of patients and was performed in only one institution. CONCLUSIONS: Dermoscopy allowed a more precise prediction of SLN status. If a combined SCOREBRESEX was used to select patients for SLNB, 41·5% of procedures might be avoided.

Electrochemotherapy in the treatment of melanoma skin metastases: a report on 31 cases.

INTRODUCTION AND OBJECTIVES: Electrochemotherapy is indicated for the treatment of unresectable cutaneous and subcutaneous tumors. The technique involves the synergistic use of electroporation of cell membranes to increase the cytotoxicity of anticancer drugs delivered to the tumor cells. The aim of this study was to analyze the clinical effectiveness and safety of electrochemotherapy in the treatment of unresectable locoregional recurrent or metastatic melanomas. MATERIAL AND METHODS: We studied 31 patients treated between January 2007 and December 2012. The European Standard Operating Procedures of Electrochemotherapy (ESOPE) were applied in all cases. Treatment response was analyzed as overall patient response (mean response based on results for all lesions treated in a given patient). RESULTS: Response was classified as partial in 49% of patients and complete in 23%. At 1 year, the level of response achieved had been maintained in 17 patients. Disease progression was observed in 28% of the series. Immediate local complications (pain, swelling, erythema) were mild and resolved within 48hours in most cases. Eight patients developed subsequent local complications, such as ulcers and secondary infections associated with necrosis of the lesions. These complications were brought under control with topical treatments. CONCLUSIONS: Electrochemotherapy is a very effective, safe, and efficient treatment for advanced locoregional disease in patients with unresectable melanoma lesions.

Polycyclic aromatic hydrocarbons in residential dust and risk of childhood acute lymphoblastic leukemia.

Several polycyclic aromatic hydrocarbons (PAHs) are known or probable human carcinogens. We evaluated the relationship between PAH exposure and risk of childhood acute lymphoblastic leukemia (ALL) using concentrations in residential dust as an exposure indicator. We conducted a population-based case-control study (251 ALL cases, 306 birth-certificate controls) in Northern and Central California from 2001 to 2007. We collected residential dust using a high volume small surface sampler (HVS3) (n=185 cases, 212 controls) or by sampling from participants' household vacuum cleaners (n=66 cases, 94 controls). We evaluated log-transformed concentrations of 9 individual PAHs, the summed PAHs, and the summed PAHs weighted by their carcinogenic potency (the toxic equivalence). We calculated odds ratios (ORs) and 95% confidence intervals (CI) using logistic regression adjusting for demographic characteristics and duration between diagnosis/reference date and dust collection. Among participants with HVS3 dust, risk of ALL was not associated with increasing concentration of any PAHs based on OR perln(ng/g). Among participants with vacuum dust, we observed positive associations between ALL risk and increasing concentrations of benzo[a]pyrene (OR perln[ng/g]=1.42, 95% CI=0.95, 2.12), dibenzo[a,h]anthracene (OR=1.98, 95% CI=1.11, 3.55), benzo[k]fluoranthene (OR=1.71, 95% CI=0.91, 3.22), indeno[1,2,3-cd]pyrene (OR=1.81, 95% CI=1.04, 3.16), and the toxic equivalence (OR=2.35, 95% CI=1.18, 4.69). The increased ALL risk among participants with vacuum dust suggests that PAH exposure may increase the risk of childhood ALL; however, reasons for the different results based on HVS3 dust samples deserve further study.

Monitoring system for isolated limb perfusion based on a portable gamma camera.

BACKGROUND: The treatment of malignant melanoma or sarcomas on a limb using extremity perfusion with tumour necrosis factor (TNF-alpha) and melphalan can result in a high degree of systemic toxicity if there is any leakage from the isolated blood territory of the limb into the systemic vascular territory. Leakage is currently controlled by using radiotracers and heavy external probes in a procedure that requires continuous manual calculations. The aim of this work was to develop a light, easily transportable system to monitor limb perfusion leakage by controlling systemic blood pool radioactivity with a portable gamma camera adapted for intraoperative use as an external probe, and to initiate its application in the treatment of MM patients. METHODS: A special collimator was built for maximal sensitivity. Software for acquisition and data processing in real time was developed. After testing the adequacy of the system, it was used to monitor limb perfusion leakage in 16 patients with malignant melanoma to be treated with perfusion of TNF-alpha and melphalan. RESULTS: The field of view of the detector system was 13.8 cm, which is appropriate for the monitoring, since the area to be controlled was the precordial zone. The sensitivity of the system was 257 cps/MBq. When the percentage of leakage reaches 10% the associated absolute error is +/-1%. After a mean follow-up period of 12 months, no patients have shown any significant or lasting side-effects. Partial or complete remission of lesions was seen in 9 out of 16 patients (56%) after HILP with TNF-alpha and melphalan. CONCLUSION: The detector system together with specially developed software provides a suitable automatic continuous monitoring system of any leakage that may occur during limb perfusion. This technique has been successfully implemented in patients for whom perfusion with TNF-alpha and melphalan has been indicated.

Prognostic value of tyrosinase reverse transcriptase PCR analysis in melanoma sentinel lymph nodes: long-term follow-up analysis.

OBJECTIVE: To determine the prognostic value of detecting tyrosinase transcripts in melanoma sentinel lymph nodes (SLNs). METHODS: Reverse transcription (RT) PCR for tyrosinase mRNA was performed on negative SLNs of 76 patients with melanoma. RESULTS: Tyrosinase mRNA was found in 39 patients (51.3%). After a median follow-up period of 51 months, significant differences were found in overall survival (OS) but not in disease-free survival (DFS). The 5-year OS and DFS rates were 97.2% and 80%, respectively, for RT-PCR tyrosinase-negative (TN) patients vs. 78.67% and 66.24% for RT-PCR tyrosinase-positive (TP) patients (P = 0.019 and P = 0.38, respectively). Of four progressing patients in the TN group, three relapsed with subcutaneous, soft-tissue or lymph-node metastases, while seven out of nine progressing patients in the TP group relapsed at visceral sites. CONCLUSIONS: No significant differences in DFS were found by RT-PCR tyrosinase expression analysis at melanoma SLNs. Significant differences in OS could be related to a different pattern of relapse and must be confirmed after a longer follow-up time.

Gamma-detecting probe used intraoperatively to locate the sentinel lymph node in patients with malignant melanoma.

OBJECTIVE: To assess the usefulness of lymphoscintigraphy and intraoperative gamma probe in the detection of sentinel lymph nodes. DESIGN: Prospective open study. SETTING: University hospital, Spain. SUBJECTS: 40 patients with malignant melanoma (24 stage I/II, 16 stage III). INTERVENTION: The day before operation a lymphoscintigram with 99mTc-nanocolloid was taken and the first lymph node identified was considered to be the sentinel node. A hand-held gamma probe was used for intraoperative mapping. MAIN OUTCOME MEASURE: Identification of the sentinel node. RESULTS: Sentinel nodes were identified in 39/40 patients (98%). In 24 patients with stage I/II disease, 34 sentinel nodes were found (6 invaded and 28 clear of melanoma). A total number of 161 regional lymph nodes were harvested, none of them invaded by melanoma. In 16 patients with stage III disease, 22 sentinel nodes were located (14 invaded and 8 clear of melanoma). A total of 89 regional lymph nodes were excised in patients with invaded sentinel nodes (44 of which were invaded and 45 clear of disease). 41 lymph nodes were excised from patients with clear sentinel nodes, and all were also clear of melanoma. CONCLUSIONS: We conclude that this is a useful technique for the selection of patients with melanoma who may require lymphadenectomy.

Intrahepatic biliary lesions after orthotopic liver transplantation.

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.

Hepatic xanthine levels as viability predictor of livers procured from non-heart-beating donor pigs.

BACKGROUND: The aim of the present study was to evaluate hepatic content of adenine nucleotides and their degradation products in non-heart-beating donor (NHBD) pigs and its relationship with recipient survival. METHODS: Thirty animals were transplanted with an allograft from NHBDs. After warm ischemia (WI) time (20, 30, or 40 min), cardiopulmonary bypass and normothermic recirculation (NR) were run for 30 min. Afterward, the animals were cooled to 15 degrees C and liver procurement was performed. RESULTS: Survival rate was 100% in the 20WI, 70% in the 30WI, and 50% in the 40WI. Livers from non-surviving animals had higher levels of xanthine after NR than livers from surviving animals. Logistic regression analysis revealed that xanthine at the end of NR was the only variable able to predict survival with a calculated sensitivity of 80% and a specificity of 60%. Prolongation of warm ischemic period leaded to a greater xanthine accumulation as well as increased plasma alpha-glutathione S-transferase levels at reperfusion. Xanthine at NR and alpha-glutathione S-transferase at reperfusion significantly correlated, indicating that donor xanthine contributes to some extent to the severity of the lesion by ischemia-reperfusion. CONCLUSIONS: It is suggested that xanthine content in the donor is able to predict survival after transplantation. Xanthine is significantly involved in the hepatic lesion elicited by warm ischemia and subsequent ischemia-reperfusion associated to liver transplantation from a NHBD.

Endogenous nitric oxide and exogenous nitric oxide supplementation in hepatic ischemia-reperfusion injury in the rat.

BACKGROUND: Although nitric oxide (NO) is thought to be beneficial in hepatic ischemia-reperfusion (I/R), the mechanisms for this effect are not well established. METHODS: To investigate the effects of endogenous NO and exogenous NO supplementation on hepatic I/R injury and their pathogenic mechanisms, serum ALT and hyaluronic acid (endothelial cell damage), and hepatic malondialdehyde and H2O2 (oxidative stress), myeloperoxidase activity (leukocyte accumulation), and endothelin (vasoconstrictor peptide opposite to NO) were determined at different reperfusion periods in untreated rats and rats receiving L-NAME, L-NAME+L-arginine, and spermine NONOate (exogenous NO donor). RESULTS: After reperfusion every parameter increased in untreated animals. Endogenous NO synthesis inhibition by L-NAME increased hepatocyte and endothelial damage as compared to untreated rats, which was reverted and even improved by the addition of L-arginine. Spermine NONOate also improved this damage. However, different mechanisms account for the beneficial effect of endogenous and exogenous NO. Oxidative stress decreased by both L-NAME and L-NAME+L-arginine, but remained unmodified by spermine NONOate. Myeloperoxidase increased by L-NAME and this effect was reverted by the addition of L-arginine, whereas no change was observed with spermine NONOate. Endothelin levels were not modified by L-NAME and L-NAME+L-arginine, but decreased with spermine NONOate. CONCLUSIONS: These results suggest that, although both endogenous and exogenous NO exert a protective role in experimental hepatic I/R injury, the mechanisms of the beneficial effect of the two sources of NO are different.

Evaluation of ischemic injury during liver procurement from non-heart-beating donors.

UNLABELLED: The aim of this study was to assess liver viability after different periods of cardiac arrest and the predictive value of two markers of ischemia-reperfusion injury. METHODS: A pig liver transplantation model of non-heart-beating donors was studied. Four donor groups were designed; three groups were submitted to different periods of cardiac arrest (20, 30 and 40 min), and the fourth group served as the control group (without cardiac arrest). In the non-heart-beating donor groups, normothermic recirculation was established 30 min prior to total body cooling. Aminotransferase, alpha-glutathione-S-transferase, and hyaluronic acid determinations as well as liver biopsies, were serially performed. RESULTS: Although hepatocellular function could be preserved after 40 min of cardiac arrest, histological lesions at 5 days were considered irreversible due to the presence of a necrotic biliary tract. An overall significant relationship was found between the time period of cardiac arrest (20, 30 or 40 min) and the levels of hyaluronic acid (p = 0.004) or alpha-glutathione-S-transferase (p = 0.01) obtained during liver procurement and transplantation. CONCLUSIONS: The period of cardiac arrest is the determinant factor of liver viability after liver transplantation from non-heart-beating donors. As early markers of endothelial or hepatocellular damage, hyaluronic acid or alpha-glutathione-S-transferase levels may help to evaluate the ischemic injury of a potential donor.

Liver conditioning after cardiac arrest: the use of normothermic recirculation in an experimental animal model.

The aim of this study was to compare the possible role of normothermic recirculation with the role of liver transplants from non-heart-beating donor pigs after 20 min of cardiac arrest. Three groups were studied, of which two were control groups: group 1, in which the liver was harvested from a heart-beating donor; group 2, in which the liver was harvested after a period of cardiac arrest followed by total body cooling; and group 3, in which the liver was procured as in group 2, but including a period of 30 min of cardiopulmonary bypass and tissue oxygenation at 37 degrees C before total body cooling. Survival at 5 days; endothelial (hyaluronic acid) and hepatocellular damage (AST, ALT, and alpha-GST); adenine nucleotides (energy charge), and histological changes were evaluated. Normothermic recirculation during 30 min showed a significant effect on survival (p = .03), endothelial damage (p < .05), and histological changes after reperfusion (p = .04). Cardiopulmonary bypass significantly increased the energy charge during the normothermic recirculation period (p = .001). Moreover, this study shows that a significant survival (100%) can be achieved with a liver allograft after 20 min of cardiac arrest. Although the liver suffers a major insult in terms of endothelial damage and hepatocellular damage, lesions caused by the ischemic injury are reversible. Histological changes also indicate lesion reversibility, since they almost disappear after 5 days.

Hepatic blood flow and oxygen extraction ratio during normothermic recirculation and total body cooling as viability predictors in non-heart-beating donor pigs.

BACKGROUND: Our aim was to evaluate the hepatic blood flows and oxygen metabolism of non-heart-beating donor (NHBD) pigs, with the use of cardiopulmonary bypass (CPB) and normothermic recirculation (NR) before total body cooling, and its relationship with recipient survival. METHODS: Thirty-five pigs were transplanted with an allograft from NHBDs. After warm ischemia (WI) time (20, 30, or 40 min), CPB and NR were run for 30 min. After this period, the animals were cooled to 15 degrees C. In the control group (20 min of WI), the period of NR was excluded. Liver procurement was then performed. RESULTS: Survival rate was 100% in the 20WI, 70% in the 30WI, and 50% in the 40WI. Control group survival rate was 0%. Hepatic artery blood flow and portal blood flow recovered during NR. Pump blood flow during CPB increased rapidly during NR and was significantly higher in the 20WI. When donors of the livers transplanted in "surviving pigs" (DSP) were compared with donors of the livers transplanted in "nonsurviving pigs" (DNSP), hepatic artery blood flow, portal blood flow, and pump blood flow were higher in the DSP. Hepatic oxygen extraction ratio increased in the three groups with respect to baseline values. Hepatic oxygen extraction ratio was lower in the 20WI than in the other groups and was lower in the DSP than in the DNSP. CONCLUSIONS: The use of a NR period before total body cooling improves survival of liver transplantation in NHBDs. Portal blood flow and pump blood flow measurements can predict the viability of the grafts.