Elevation of hepatocyte growth factor levels in portal and hepatic veins immediately after hepatic resection in cirrhotic patients.
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Publications and source records attributed to H Itasaka.
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Prostanoids such as prostacyclin and thromboxane A2 have recently been suggested to play important roles in cold ischemia/reperfusion injury. The purpose of this study was to investigate the effect of thromboxane A2 synthetase inhibitor (OKY-046) on cold-stored livers of the rat using an ex vivo perfusion system. Addition of OKY-046 to preservation solution and the perfusate of livers stored cold (4 degrees C) in lactated Ringer's solution resulted in significantly lower glutamic pyruvic transaminase release (3.01 +/- 0.86 IU/g liver vs. 1.79 +/- 1.08 IU/g liver at 120 min after perfusion; P < 0.05), reduced perfusate ammonia levels (8.51 +/- 2.51 micrograms/dl/g liver vs. 3.62 +/- 1.71 micrograms/dl/g liver at 60 min; P < 0.05 and thereafter), lower perfusate taurocholate levels (0.63 +/- 0.10 vs. 0.18 +/- 0.05 at 15 min; P < 0.01 and thereafter), perfusate hyaluronic acid clearance (0.934 +/- 0.132 vs. 0.76 +/- 0.127 at 30 min; P < 0.05 and thereafter), and a reduced number of trypan blue-positive sinusoidal lining cells (50.1 +/- 9.9%; vs. 17.4 +/- 7.0%; P < 0.01). Histologically, the liver preserved for 6 hr in simple cold lactated Ringer's solution exhibited interstitial edema, various degrees of hepatocyte swelling, and sinusoidal stenosis, as well as dilatation, while the livers treated with OKY-046 demonstrated much less hepatocyte swelling, and change in sinusoidal width was nearly absent. We conclude that OKY-046 reduces post-preservation reoxygenation injury by protecting sinusoidal endothelial cells and hepatocytes.
BACKGROUND: Protein induced by vitamin K absence or antagonist II (PIVKA-II) was widely used as a diagnostic marker for hepatocellular carcinoma (HCC), however, its prognostic value is unclear. The authors evaluated PIVKA-II clinicopathologically as a prognostic marker for HCC. METHODS: The relationship between pathologic prognostic factors and plasma PIVKA-II and alpha-fetoprotein (AFP) was investigated in 72 patients with resectable HCC measuring less than 6 cm in greatest dimension. RESULTS: PIVKA-II shows significantly lower sensitivity, but higher specificity than AFP, and the use of these two complementary markers appears to be useful in the diagnosis of HCC. The frequencies of intrahepatic metastasis, portal vein tumor thrombus, hepatic vein tumor thrombus, and capsular infiltration were significantly higher in patients with positive PIVKA-II than in those with negative-PIVKA-II, and the recurrence-free rate was significantly lower in patients with positive rather than with negative PIVKA-II. However, there were no significant differences between the patients who were AFP positive and those who were AFP negative in pathologic prognostic factors and the recurrence-free rate. From univariate and multivariate analyses, the authors find that PIVKA-II is one of the risk factors for recurrence of HCC after hepatectomy. CONCLUSIONS: PIVKA-II may be a useful marker for the prediction of intrahepatic spread and for the prognosis of HCC. In addition, PIVKA-II-positive patients, thus, need aggressive postoperative adjuvant therapy for undetectable residual tumors and careful postoperative monitoring to enable the early recognition of recurrence.
The use of polyethylene glycol (PEG) in preservation solutions has been associated with a decreased incidence of rejection in clinical and experimental organ transplantation. In this study, we examined the effect of PEG with different molecular configurations on rejection of small bowel allografts in the rat. Male ACI and LEW rats were used as donors and recipients, respectively. Orthotopic small bowel transplantation was performed using the following preservation solutions: lactated Ringer's solution (n = 7), University of Wisconsin solution (n = 7), University of Wisconsin solution without hydroxyethyl starch (sUW; n = 7), sUW with PEG20M (n = 9), sUW with PEG8000 (n = 6), and sUW with PEG20L (n = 7). No immunosuppression was given. In orthotopic small bowel transplantation, only groups with a high molecular weight PEG, PEG20M and PEG20L, demonstrated longer survival (P < 0.01 and P < 0.001, respectively) and delayed onset of unkempt appearance (P < 0.05 and P < 0.001, respectively). In heterotopic small bowel transplantation, sUW was compared with sUW with PEG20L. Rejection occurred later and its progression was slower in the sUW with PEG20L than in the sUW alone. Our observations suggest that the onset and progression of rejection after small bowel transplantation were influenced by the molecular weight and configuration of the PEG molecule. The mechanism is unclear, but high molecular weight PEG appears to reduce or change the immunogenicity of the small bowel allograft.
We studied the significance of tissue-type plasminogen activator (tPA) on the pretransplant assessment of liver graft viability in rats. The liver grafts were excised from the rats and then divided into two groups. Group 1 consisted of grafts preserved for 4 h in chilled, lactated Ringer's solution (4 degrees C) and group 2 consisted of grafts preserved for 6 h in the same solution. After preservation, the liver grafts were flushed out through the portal vein using 5 ml of chilled, lactated Ringer's solution (4 degrees C). The entire effluent from the hepatic veins was then collected and analyzed for tPA, ammonia, lactate, pyruvate, glutamic oxaloacetic transaminase, and lactate dehydrogenase. The tPA concentration of effluent in group 2 was significantly higher than that in group 1 (0.80 +/- 0.23 ng/ml vs 0.42 +/- 0.08 ng/ml, P < 0.05). The lactate, pyruvate, and ammonia levels in group 2 were also higher than those in group 1 (134 +/- 13 mg/dl vs 120 +/- 2 mg/dl, 0.34 +/- 0.40 mg/dl vs 0.09 +/- 0.01 mg/dl, and 183 +/- 79 micrograms/dl vs 102 +/- 40 micrograms/dl, respectively). However, the discriminative power of tPA was stronger than that of the other parameters. Histological findings revealed a higher number of trypan blue-stained sinusoidal lining cells that were detached and swollen in group 2. We conclude that the amount of tPA in the effluent flushed from the graft can serve as a sensitive and reliable indicator of cold-preserved liver grafts in rats.
A simple outpatient follow-up system was developed with a laptop personal computer to assist management of patients with hepatocellular carcinoma after hepatic resections. Since it is based on a non-relational database program and the graphical user interface of Macintosh operating system, those who are not a specialist of the computer operation can use it. It is helpful to promptly recognize current status and problems of the patients, to diagnose recurrences of the disease and to prevent lost from follow-up cases. A portability of the computer also facilitates utilization of these data everywhere, such as in clinical conferences and laboratories.
The factors related to the initiation of fibrinolysis, especially with regard to the tissue-type plasminogen activator (tPA) and the plasminogen activator inhibitor-1 (PAI-1), were investigated in 15 patients who underwent hepatic resection, and the findings were compared between those with normal livers and those with diseased livers. It was found that tPA increased before hepatic division, whereas PAI-1 increased after hepatic division and reached a peak immediately following the operation. Plasminogen decreased during hepatectomy, reaching its lowest point on postoperative day 1, and increasing later. Decreased levels of both plasminogen and the alpha 2-plasmin inhibitor were considered to be partly due to plasmin formation in the blood. Patients with a diseased liver tended to have higher intraoperative values of euglobulin lysis activity and higher postoperative values of plasminogen activator, but significantly lower postoperative values of alpha 2-plasmin inhibitor than those with a normal liver. The results of this study suggest that activation of the fibrinolytic system occurs both during hepatectomy and in the early postoperative period, and that patients with a diseased liver are prone to develop hyperfibrinolysis during hepatectomy. Moreover, the increased levels of both tPA and PAI-1 can serve as one of the most sensitive markers for the vital reaction against surgical stress.
For the assessment of graft viability, serum hyaluronic acid (HA) levels during porcine orthotopic liver transplantation were measured in two groups: group 1 (viable: n = 5) in which allografts were transplanted following a minimal cold (4 degrees C) preservation, and group 2 (nonviable: n = 4) in which allografts were transplanted after cold static storage (4 degrees C) for 24 h in University of Wisconsin solution. The changes in the HA levels reached a significant difference between the two groups at 30 min after reperfusion (P < 0.02). In group 1, all animals survived for over 4 days, while all animals in group 2 died within 24 h. The serum HA also demonstrated a significant correlation with prothrombin time, beta-glucuronidase, and aspartate aminotransferase at 120 min after reperfusion. These results suggest that the measurement of serum HA is a potentially effective index for evaluating hepatic allograft viability.
The regenerative capacity of the liver was assessed using a volumetric method on computed tomography in 21 adults: 16 underwent a standard right hepatic lobectomy for hepatocellular carcinoma, there were hepatic metastases in 3 others, and 2 suffered from other diseases. The patients' ages ranged from 33 to 68 years with a mean age of 57.0 years. The regeneration rate was expressed as the rate of the volume increase of the remnant left lobe compared with the preoperative volume of the left lobe. A univariate regression analysis showed that the portal pressure had a highly inverse correlation with the regeneration rate of the liver (r = -0.4753, P = 0.0397), while a multiple regression analysis demonstrated the correlation between the portal pressure, age, and the regeneration rate (multiple r = 0.5640). The regeneration rate of the normal liver (97.6 +/- 53.5%) was significantly higher than that of the chronic hepatitic (43.0 +/- 40.7%), and also tended to be higher than that of the cirrhotic liver (51.5 +/- 13.2%). However, there were no differences between chronic hepatitic and cirrhotic livers. The portal pressure before hepatectomy of the normal liver (149 +/- 19 mmH2O) was significantly lower than those of chronic hepatitic (188 +/- 38 mmH2O) and cirrhotic (245 +/- 78 mmH2O) livers. We thus conclude that the regenerative capacity of the liver following a right hepatic lobectomy could be estimated on the basis of both portal pressure and age. The regenerative capacity was also influenced by underlying liver diseases.
Portal pressures were estimated non-invasively in 100 patients who underwent hepatic resection and completely fulfilled the 21 variables evaluated. Ten variables were selected from among all those in the univariate analysis, and a stepwise discriminant analysis revealed four independent significant variables, namely: The indocyanine green dye retention test at 15 min (ICGR15); the prothrombin time index; the platelet count; and the globulin fraction. An equation to estimate the portal pressure was made using the coefficients in the analysis, the reliability of which was confirmed (r = 0.70484, P = 0.0001). The univariate analysis revealed ten significant variables to discriminate portal hypertension, defined as a portal pressure of over 200 mmH2O. A multiple logistic regression analysis of these variables revealed two independent variables, being ICGR15 and the platelet count. Thus, we consider that our equation for estimating portal pressure is potentially useful, and that the platelet count and ICGR15 are the most significant parameters in discriminating between the presence or absence of portal hypertension. Moreover, a platelet count of less than 120 x 10(3)/mm3 and an ICGR15 value of more than 15% correlated well with portal hypertension.
To identify the risk factors predicting major postoperative complications from among preoperative and intraoperative variables, an extensive retrospective analysis of 209 patients who underwent hepatic resections was performed using multivariate logistic regression. The major complications were defined as liver failure, intractable ascites and pleural effusion, intraperitoneal infection, intra-abdominal hemorrhage requiring reoperation, major bile leakage, and gastrointestinal tract bleeding. First, detailed pre- and intraoperative data including medical history, laboratory data, portion and extent of hepatectomy, operative time, and amount of blood loss were univariately analyzed. Next, any significant variables were multivariately analyzed using the logistic regression method. Diabetes, increased intraoperative blood loss, resection of segment 8, and an increased serum blood urea nitrogen level were independent and significant variables predicting major postoperative complications. A higher level of serum cholesterol and a procedure involving a portion of left lateral segment were found to decrease the risk. Both more careful operative procedures and intensive management of DM and renal dysfunction in the perioperative period could result in a better quality of life after hepatic resection.
A comparison of 60 blood transfused and 71 nonblood transfused hepatic resection patients was done to evaluate strategies for reducing blood transfusions during hepatic surgery. There were no significant differences between the two groups with regard to preoperative laboratory data, except for prothrombin time and hematocrit value. The mean operative blood loss was 1990 ml and 760 ml in the blood transfused and nonblood transfused groups, respectively. A multivariate analysis suggested that the patient's body weight, preoperative prothrombin time, and operative blood loss independently predicted the need for intraoperative blood transfusion. Major postoperative complications developed more frequently in the blood transfused group than in the nonblood transfused group (31.7 vs. 11.3%, p < 0.005). These results suggest that the difference in operative blood loss between the two groups was related to the prolonged prothrombin time and a susceptibility for blood transfusion was found to exist particularly in patients with a lower hematocrit value as well as a lower body weight. Thus, the improvement of these preoperative laboratory data combined with avoiding the use of the hematocrit value as a determining factor for intraoperative transfusion could correspond to a reduction in operative blood loss, while curtailing the demands on blood bank facilities, and lowering the risk of postoperative complications.
We experienced two patients with a prosthetic heart valve, who underwent hepatic resection for hepatoma while on anticoagulation therapy. Patients with a prosthetic heart valve have the following characteristics; an increased risk of thromboembolism due to diminished anticoagulation in the perioperative period, a greater risk of endocarditis due to the artificial material in the heart, and impaired cardiopulmonary function including possible arrhythmia and heart failure. Furthermore, when such patients also have liver cirrhosis with a hepatoma, there is an increased risk of perioperative bleeding while on anticoagulation due to coagulopathy and also a risk of infection due to decreased cellular immunity. Patients with a prosthetic heart valve therefore require special care and attention whenever they have to undergo hepatic resection. With respect to anticoagulation, a minimal level is required to prevent bleeding and thromboembolism. Warfarin being administered preoperatively may be switched to heparin while closely monitoring the activated clotting time (biomaterial valve: 130-150 sec, non-biomaterial valve: 150-180 sec); the heparin should then be changed back to warfarin immediately after starting oral intake following operation. For the prevention of infection, a broad spectrum antibiotic should be used prophylactically both intra-operatively and postoperatively. The cardiopulmonary function must also be carefully monitored. For the assessment of postoperative liver function, lecithin: cholesterol acyltransferase, serum bilirubin and albumin are useful because there is no relevance of coagulation parameters such as prothrombin time under anticoagulation.
We designed this study to estimate the degree of liver cirrhosis using clinical parameters and surgically resected specimens. One hundred and twenty-nine cases who underwent hepatic resection in the Department of Surgery II, Kyushu University Hospital during the period between April 1985 and July 1991 for whom data for all 29 variables evaluated were available, were admitted to this study. On the basis of the histological findings of fibrosis of the liver, the non-neoplastic part of the resected specimens were classified into 3 groups; Z0, no cirrhosis (n = 63), Z1, mild cirrhosis (n = 38), and Z2, severe cirrhosis (n = 28). A univariate analysis revealed 14 significant variables. After multiple logistic regression analysis of these, five independent variables (low platelet count, female, low value of hepaplastin test, a high Pugh's score and a high value of ICG) were identified. We obtained a fibrosis score using the coefficient of each above-mentioned variable. This score increased the discriminative power. The fibrosis score is therefore considered useful for estimating the severity of liver cirrhosis.
The protein C anticoagulant pathway in hepatic resection was studied. The patients were divided into two groups--group 1 consisted of patients with a normal liver and group 2 consisted of patients with either hepatitic or a cirrhotic liver. Plasma protein C activity and soluble thrombomodulin were then sequentially measured during hepatectomy and in the early postoperative period. The protein C activity in group 1 decreased during hepatectomy and reached a low immediately after operation, and thereafter, recovered to near preoperative levels. However, the preoperative value in group 2 was lower than that in group 1 and the postoperative values were significantly lower than those in group 1 (p < 0.05). The level of soluble thrombomodulin in group 1 decreased during hepatectomy but later returned to preoperative levels. However, in group 2, the preoperative value was higher than that in group 1 and the postoperative values were greater than that of the preoperative values, while the values were significantly higher than those in group 1 (p < 0.05). During hepatectomy, hypercoagulability may contribute to the low levels of protein C and soluble thrombomodulin. The postoperative significant increase of soluble thrombomodulin may, thus, indicate the occurrence of endothelial injury in the remnant liver. The sequential measurements of both parameters can, therefore, be useful in detecting coagulopathy and endothelial injury in hepatic resection.
BACKGROUND: The significance of repeat hepatectomy for recurrent hepatocellular carcinoma remains controversial. Therefore the aim of this study was to reevaluate both the survival and the surgical risks of repeat hepatectomy. METHODS: The significance of repeat hepatectomy including the survival and the surgical risks for recurrent hepatocellular carcinoma were investigated with 21 patients who underwent a curative repeat hepatectomy during the period between May 1975 and July 1993. For a comparison of survival, 253 patients who underwent a curative primary hepatectomy during the period between April 1985 and July 1993 were used. Moreover, the preoperative liver function tests were also compared between the first and second hepatectomies. RESULTS: Regarding the preoperative liver function tests, the indocyanine green dye excretion rate at 15 minutes in the second hepatectomy (18.7% +/- 8.7%) was significantly higher than that in the first hepatectomy (14.7% +/- 5.9%). With regard to the surgical risks, there was no difference in the clinical parameters for blood loss, operation time, and the incidence of postoperative complications between the first and second hepatectomies. The postoperative hospital stay for the second hepatectomies was relatively shorter than that for the first hepatectomies. In addition, the patient's survival and disease-free survival after a curative repeat hepatectomy were almost identical to that after a curative primary hepatectomy. CONCLUSIONS: A curative repeat hepatectomy is thus considered to be the most effective therapeutic modality for recurrent hepatocellular carcinoma.
To investigate the characteristics, risk factors, and prevention of methicillin-resistant Staphylococcus aureus (MRSA), a total of 3,627 patients were studied. Among these, 1,336 patients with various infections were used in a risk factor analysis of MRSA to determine the relationship between the use of antibiotics and the incidence of MRSA. Only 3.0% of infections were attributed to MRSA, the esophagus and colorectal region being highly involved, as anastomotic or pelvic abscesses, while the lung had a lower incidence. Almost half the patients with MRSA infections (47.6%) had concomitant infection. A univariate analysis revealed the following significant factors: The coexistence of gastrointestinal or metastatic malignancy, sepsis, tracheostomy, and the prior use of antibiotics such as the beta-lactam compounds or aminoglycosides. A multivariate analysis showed that gastrointestinal malignancy, sepsis, and the prior use of aminoglycosides, tetracycline, macrolides, and carbapenems were independently significant factors. To promote the education of doctors and nurses, regular in-service meetings on MRSA were held in the ward. Moreover, preventive approaches such as patient isolation, strategically placed hand washing equipment, and the use of disposable gloves and contaminated waste bags, have been initiated, and the incidence of MRSA has decreased significantly since then. Thus, to control MRSA, the following steps should be taken: (1) constant and careful surveillance, (2) regular risk factor analyses, (3) the optimal administration of antibiotics, and (4) the education of all hospital staff.