BACKGROUND/AIMS: Hepatopulmonary syndrome is defined as a clinical triad including chronic liver disease, abnormal pulmonary gas exchange resulting ultimately in profound arterial hypoxaemia, and evidence of intrapulmonary vascular dilatations. We report five patients with liver cirrhosis diagnosed with hepatopulmonary syndrome who had associated chronic obstructive or restrictive respiratory diseases. METHODS: Clinical, radiographic and constrast-enhanced echocardiographic findings, and systemic and pulmonary haemodynamic and gas exchange, including ventilation-perfusion distributions, measurements were assessed in all five patients. RESULTS: Echocardiography was consistent with the presence of intrapulmonary vasodilation without intracardiac abnormalities, and high resolution computed tomographic scan features were compatible with clinical (3 cases) or histopathological diagnoses (2 cases) of associated respiratory disorders. The most common prominent functional findings were moderate to severe arterial hypoxaemia, caused by moderately to severely increased intrapulmonary shunting and/or mild to moderate low ventilation-perfusion areas, and hypocarbia along with an increased cardiac output and a low pulmonary artery pressure and vascular resistance. CONCLUSIONS: These functional characteristics, classically reported in the setting of clinically stable, uncomplicated hepatopulmonary syndrome, conform to a distinctively unique, chronic gas exchange pattern. Equally important, these pulmonary haemodynamic-gas exchange hallmarks are not influenced by the co-existence of chronic cardiorespiratory disease states. These data may have clinical relevance for elective indication of hepatic transplantation in patients with life-threatening hepatopulmonary syndrome.

Adult↗

PubMed1999

Severe portopulmonary hypertension after liver transplantation in a patient with preexisting hepatopulmonary syndrome.

BACKGROUND: Portopulmonary hypertension and hepatopulmonary syndrome have been considered mutually exclusive pulmonary vascular disorders in liver disease states. METHODS: This current report describes a middle-aged patient, a candidate for liver transplantation, diagnosed with hepatopulmonary syndrome on the basis of clinical, echocardiographic and gas exchange criteria. Unusually high pulmonary pressures were observed at liver transplantation, performed 6 months after the initial diagnosis of hepatopulmonary syndrome. Three months later, the patient developed severe pulmonary hypertension and died of right ventricular failure during a second attempted liver transplantation. Postmortem histologic findings in the lung confirmed the presence of plexogenic pulmonary arteriopathy. CONCLUSION: This case illustrates the potential occurrence of hepatopulmonary syndrome and portopulmonary hypertension in the same patient, suggesting that the presence of hepatopulmonary syndrome may not preclude the development of portopulmonary hypertension.

Hepatopulmonary Syndrome↗

PubMed1999

Effects of end-to-side portacaval shunt and distal splenorenal shunt on systemic and pulmonary haemodynamics in patients with cirrhosis.

BACKGROUND: Patients with cirrhosis exhibit splanchnic, peripheral and pulmonary vasodilation, which are thought to play a role in increasing portal pressure, promoting sodium retention and determining arterial hypoxaemia. The present study investigated whether these abnormalities are influenced by portal hypertension or by portal systemic shunting. METHODS: Sixty-one patients with cirrhosis who had haemodynamic measurements before and after end-to-side portacaval shunt (n = 30) or distal splenorenal shunt (n = 31) were evaluated. RESULTS: End-to-side portacaval shunts were more effective than distal splenorenal shunts in decompressing the portal system (portocaval pressure gradient 3.2 +/- 2.5 vs splenocaval gradient 6.5 +/- 3.2 mmHg, P < 0.0001), because of a greater shunt blood flow (33 +/- 12 vs 21 +/- 12 mL/min per kg, P < 0.005). Azygos blood flow and hepatic blood flow decreased significantly after both surgical shunts. However, end-to-side portacaval shunts caused a greater decrease in peripheral resistance than distal splenorenal shunts (-23 +/- 18 vs -11+/- 27%, P < 0.05). Mean arterial pressure and pulmonary vascular resistance were significantly reduced after an end-to-side portacaval shunt (-7 +/- 10%, P < 0.001 and -14 +/- 33%, P < 0.004, respectively), but not after splenorenal shunt. CONCLUSIONS: These results show that end-to-side portacaval shunts, despite normalizing portal pressure, worsen the peripheral and pulmonary vasodilatation. The splenorenal shunt that maintained a higher portal pressure, caused less peripheral vasodilatation and did not enhance pulmonary vasodilatation. These findings suggest that portal systemic shunting is more important than increased portal pressure in determining peripheral vasodilatation in cirrhosis.

Adult↗

PubMed1999

Deterioration of esophageal motility with age: a manometric study of 79 healthy subjects.

OBJECTIVE: Data are limited on the effect of age on esophageal function. We evaluated whether aging influences the motor activity of the esophagus. METHODS: Standard esophageal manometry was performed in 79 healthy, nonpaid volunteers of both sexes, 18-73 yr of age. Lower (LES) and upper esophageal sphincter (UES) characteristics and the properties of esophageal peristaltic waves were assessed by age groups: < or = 25 yr, 26-35 yr, 36-45 yr, 46-55 yr, 56-65 yr, and > 65 yr. RESULTS: Age correlated inversely with LES pressure and length, UES pressure and length, and peristaltic wave amplitude and velocity, and correlated directly with the proportion of simultaneous contractions. Age was inversely correlated with the upper limits of normality (95th percentiles) of LES pressure (r = -0.943, p = 0.005), UES pressure (r = -0.943, p = 0.005), middle and lower peristaltic wave amplitude (r = -0.947, p = 0.004, and r = -0.844, p = 0.035, respectively), upper/middle peristaltic progression speed (r = -0.943, p = 0.005), and the proportion of simultaneous contractions (r = 0.926, p = 0.008), but not with the lower normal limits (5th percentiles) of these variables. Gender did not affect esophageal motility variables. The 95th percentiles of LES pressure differed by 20 mm Hg, those of lower peristaltic amplitude by 82 mm Hg, and those of percent simultaneous contractions by a factor of 2, between the younger and the older age groups. CONCLUSIONS: The results suggest that normal esophageal motility deteriorates with advancing age. Thus, age-related normality limits of esophageal pressures should be considered before establishing the manometric diagnosis of hypercontractile esophageal motility disorders.

Adolescent↗

PubMed1999

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.

Alanine Transaminase↗

PubMed1998

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.

Animals↗

PubMed1998

Evidence from transgenic mice that interferon-beta may be involved in the onset of diabetes mellitus.

A number of cytokines have been shown to alter the function of pancreatic beta-cells and thus might be involved in the development of type 1 diabetes. Interferon-beta (IFN-beta) expression is induced in epithelial cells by several viruses, and it has been detected in islets of type 1 diabetic patients. Here we show that treatment of isolated mouse islets with this cytokine was able to alter insulin secretion in vitro. To study whether IFN-beta alters beta-cell function in vivo and leads to diabetes, we have developed transgenic mice (C57BL6/SJL) expressing IFN-beta in beta-cells. These mice showed functional alterations in islets and impaired glucose-stimulated insulin secretion. Transgenic animals presented mild hyperglycemia, hypoinsulinemia, hypertriglyceridemia, and altered glucose tolerance test, all features of a prediabetic state. However, they developed overt diabetes, with lymphocytic infiltration of the islets, when treated with low doses of streptozotocin, which did not induce diabetes in control mice. In addition, about 9% of the transgenic mice obtained from the N3 back-cross to outbred albino CD-1 mice spontaneously developed severe hyperglycemia and hypoinsulinemia and showed mononuclear infiltration of the islets. These results suggest that IFN-beta may be involved in the onset of type 1 diabetes when combined with either an additional factor or a susceptible genetic background.

Animals↗

PubMed1998

Liver transplantation for small hepatocellular carcinoma: the tumor-node-metastasis classification does not have prognostic power.

Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors < or = 5 cm without vascular invasion, thus avoiding the use of the tumor-node-metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 +/- 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 +/- 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 +/- 45.1 days). The pathological tumor-node-metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1-, 3-, and 5-year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long-term prognosis.

Adult↗

PubMed1998

Vena cava vascular reconstruction during orthotopic liver transplantation: a comparative study.

The aim of this study was to evaluate the influence of preserving the recipient's inferior vena cava during orthotopic liver transplantation (OLT) on hemodynamic alterations, blood component requirements, postoperative liver and renal function, as well as vascular-related complications. A total of 122 OLTs was studied. In 35 OLTs, venovenous bypass (BP) was used; in 35 OLTs, bypass was not used (NBP); and in 52 OLTs, the recipient's inferior vena cava was preserved (PC). Preservation of the inferior vena cava means that venous return is not compromised at any time during transplantation. The time of hepatectomy was not different among the three groups (208 +/- 11, 188 +/- 13, and 194 +/- 6 minutes for BP, NBP, and PC, respectively); however, the total operating time was significantly lower in PC patients (492 +/- 24, 459 +/- 18, and 419 +/- 10 minutes for BP, NBP, and PC, respectively; P = .004, ANOVA). Blood component requirements were significantly lower in patients with PC. For red blood cells, these were 15.2 +/- 2.6, 16 +/- 3.4, and 7.1 +/- 1.5 units for BP, NBP, and PC, respectively (P = .009, ANOVA), and for fresh-frozen plasma, these were 5.4 +/- .7, 5.8 +/- .9, and 3 +/- .4 L for BP, NBP, and PC, respectively (P = .005, ANOVA). Postoperative liver and renal function did not differ among the three groups. The incidence of surgical complications (bleeding and vascular) was similar. Preservation of the inferior vena cava of the recipient significantly reduces the magnitude of OLT.

Blood Transfusion↗

PubMed1998

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.

Adenine Nucleotides↗

PubMed1998

Unusual intraoperative complication in laparoscopic sigmoidectomy.

The authors report a case of complete rotation of the left colon after laparoscopic sigmoidectomy. Such an uncommon complication in open colectomies has not been previously described with the laparoscopic approach. During the performance of laparoscopic-assisted colectomies the proximal segment of the colon can be rotated when removing the specimen through a small incision. Therefore we recommend inspecting the position of the colon before the stapler is fired.

Adult↗

PubMed1998

Port site metastases and recurrence after laparoscopic colectomy. A randomized trial.

BACKGROUND: This study was performed to prospectively assess the impact of the laparoscopic approach to the patterns of port site metastases (PSM) and recurrence rate (RR) of resected colon carcinomas as compared with conventional colectomies. METHODS: All patients were included in a prospective randomized trial comparing laparoscopic-assisted colectomy (LAC) versus open colectomy (OC) for colon cancer. The randomization was stratified for localization of the lesion. Patients with metastasic disease at time of the surgery were excluded. Follow-up in the outpatient clinic was done every 3 months for a minimum of 12 months. Endpoints for the study were metastasis at port site and laparotomy incision as well as recurrence rate. RESULTS: Of 91 segmental colectomies performed from November 1993 to January 1996, there were 44 LAC and 47 OC. Patient data were similar in both groups (age, sex, Dukes stage, type of operation). Mean follow-up was 21.4 months, with a range of 13 to 41 months. There were no wounds or PSM in those series. RR was similar for both groups. For LAC, it was five of 31 (16.1%); for OC, it was six of 40 (15%). CONCLUSIONS: The laparoscopic approach has a recurrence rate similar to that for open procedures for colon cancer. However, additional follow-up of these patients is needed before we can determine whether or not the laparoscopic approach influences overall survival.

Aged↗

PubMed1998

Effects of carbon dioxide vs helium pneumoperitoneum on hepatic blood flow.

BACKGROUND: Elevated intraabdominal pressure due to gas insufflation for laparoscopic surgery may result in regional blood flow changes. Impairments of hepatic, splanchnic, and renal blood flow during peritoneal insufflation have been reported. Therefore we set out to investigate the effects of peritoneal insufflation with helium (He) and carbon dioxide (CO2) on hepatic blood flow in a porcine model. METHODS: Twelve pigs were anesthetized and mechanically ventilated with a fixed tidal volume after the stabilization period. Peritoneal cavity was insufflated with CO2 (n = 6) or He (n = 6) to a maximum intraabdominal pressure of 15 mmHg. Hemodynamic parameters, gas exchange, and oxygen content were studied at baseline, 90 mm and 150 min after pneumoperitoneum, and 30 min after desufflation. Determination of hepatic blood flow with indocyanine green was made at all measured points by a one-compartment method using hepatic vein catheterization. RESULTS: A similar decrease in cardiac output was observed during insufflation with both gases. Hepatic vein oxygen content decreased with respect to the baseline during He pneumoperitoneum (p < 0.05), but it did not change during CO2 insufflation. Hepatic blood flow was significantly reduced in both the He and CO2 pneumoperitoneums at 90 min following insufflation (63% and 24% decrease with respect to the baseline; p < 0.001 and p < 0.05, respectively) being this decrease marker in the He group (p = 0.02). CONCLUSIONS: These findings suggest that helium intraperitoneal insufflation results in a greater impairment on hepatic blood flow than CO2 insufflation.

Animals↗

PubMed1998

Liver transplantation in patients with non-biliary cirrhosis: prognostic value of preoperative factors.

BACKGROUND/AIM: The type of disease indicating liver transplantation is one of the most powerful predictors of postoperative survival. This may be an important problem in evaluating the prognostic significance of other factors when patients with liver diseases of very different nature are jointly studied. To minimize this bias, the present study aimed to investigate preoperative prognostic factors in liver transplantation only in patients with non-biliary cirrhosis. METHODS: Twenty-three preoperative standard clinical and laboratory variables were analyzed as possible prognostic factors in 162 patients receiving liver transplantation for non-biliary cirrhosis. Data for seven splanchnic and systemic hemodynamic variables were also analyzed in 55 patients. RESULTS: Using univariate analyses followed by a multivariate analysis, only preoperative blood urea nitrogen (BUN) reached statistical significance as an independent predictor of hospital survival; the survival rate at the end of hospitalization being 90% in patients with BUN< or =25 mg/dl and 65% in patients with BUN>25 mg/dl (p=0.0008). Similarly, preoperative BUN was the only variable independently predicting cumulative long-term survival, with an 87% survival probability at 1 year and 73% at 4 years in patients with BUN< or =25 mg/dl, and 61% and 49%, respectively, in patients with BUN>25 mg/dl (p=0.0014). CONCLUSIONS: Renal function parameters are the most powerful preoperative predictors of survival after liver transplantation in patients with non-biliary cirrhosis. It is suggested that liver transplantation is indicated in these patients before marked renal dysfunction develops.

Adult↗