Transoral ultrasonographic evaluation of carotid flow in predicting cerebral hemodynamics after carotid endarterectomy.

PURPOSE: We investigated whether measurement of blood flow in the extracranial distal internal carotid artery (ICA) by transoral carotid ultrasonography (TOCU) can predict the cerebral hemodynamics and the hemodynamic effect of carotid endarterectomy (CEA) in patients with unilateral carotid stenosis. METHODS: Forty-nine patients with unilateral ICA stenosis who underwent CEA were studied. Preoperative blood flow in the poststenotic portion of the extracranial ICA was studied by using TOCU. Regional cerebral blood flow (rCBF) and vasoreactivity to acetazolamide (VR) in the territory of the middle cerebral artery were investigated by using single-photon emission CT (SPECT) before, 2 weeks after, and 3 months after CEA. RESULTS: Doppler flow velocities in the extracranial distal ICA measured transorally by TOCU correlated with baseline as well as postacetazolamide rCBF in the ipsilateral side (regression analysis, P < .05). Diameter and blood flow volume in the extracranial distal ICA were associated with ipsilateral postacetazolamide rCBF and VR (regression analysis, P < .05). When the patients were divided into 2 groups according to the ICA volume flow distal to a carotid stenosis, group I < 3.5 mL/s and group II > 3.5 mL/s, ipsilateral postacetazolamide rCBF in group I was significantly lower than that in group II (P = .008). Ipsilateral postacetazolamide rCBF (analysis of variance [ANOVA], P = .02) and VR (ANOVA, P = .03) significantly improved after CEA for 3 months in group I but not in group II. CONCLUSION: TOCU can detect the decrease in poststenotic flow of the distal extracranial ICA that is indicative of impaired intracranial hemodynamics and predictive for improvement of cerebral blood flow after CEA in patients with unilateral carotid stenosis.

Beneficial effect of thromboxane A2 synthetase inhibitor on cold-stored rat liver.

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.

The impact of donor age on living donor liver transplantation.

BACKGROUND: The impact of the age of the donor on the outcome of living related liver transplantation is yet to be clarified. METHODS: During October 14, 1996 and December 20, 1999, 34 living related liver transplantations were performed. Of these, 26 cases were performed using the extended left lobe graft, which were classified into three groups; younger donor group (group Y, donor age < 30, n = 7), middle-aged donor group (group M, 30 < or = donor age <50, n=13), and older donor group (group O, donor age < 50, n = 6). Early allograft function and regeneration were compared between these groups. RESULTS: There was no difference in standard liver volume, and predicted or harvested graft size between the three groups. Although serum transaminase and total bilirubin levels within postoperative day 7 were not different between the groups, the prothrombin time on postoperative day 3 was significantly longer in group O than in group Y. One week after transplantation, group Y had significantly greater graft/standard liver volume ratio than group O, and greater graft volume than group M and O. One month after transplantation, however, there was no significant difference in such graft size parameters between the groups. Graft and patient survival were comparable between the three groups. CONCLUSION: Although function and regeneration of the allografts from older donors in living donor liver transplantation is worse than those of their younger counterparts, the outcome is not affected by the age of the liver.

Prolonged preservation in University of Wisconsin solution associated with hepatic artery thrombosis after orthotopic liver transplantation.

Hepatic artery thrombosis (HAT) after liver transplantation (LTx) usually mandates retransplantation. Prolonged preservation with Eurocollins solution has been associated with HAT. We reviewed our experience with 359 LTx patients to identify risk factors for HAT. All grafts were preserved in University of Wisconsin solution. HAT developed in 12 patients (3%) within 50 days. Seven patients were asymptomatic; four presented with biliary sepsis and 1 with poor graft function. Two patients had suffered acute rejection; another 2 had severe preservation injury. Technical problems accounted for 4 cases; in the remaining 8, no etiology was found. Diagnosis was at a mean 14.7 days after LTx. One patient maintains normal graft function 3 years after LTx without intervention. Eight underwent re-LTx, 3 of whom died. Routine surveillance via duplex enabled early diagnosis and revascularization in 3 patients; in all 3, no biliary complications occurred between 6 and 20 months. Overall graft and patient survival after HAT were 33.3% and 75%, respectively. Cold ischemic time (CIT) averaged 813 min in patients with HAT and 669 min in those without HAT (P < .05). HAT occurred in 7/165 patients with CIT > 12 hr, and in 3/234 patients with CIT < 12 hr (P = 0.0699). By avoiding CIT > 12 hr, we have recently avoided HAT in 78 consecutive patients. We conclude that CIT > 12 hr may increase the risk of HAT. When HAT is diagnosed before biliary sepsis develops, flow can often be restored and retransplantation averted.

Obviation of prereperfusion rinsing and decrease in preservation/reperfusion injury in liver transplantation by portal blood flushing.

Liver allografts are traditionally rinsed with cold lactated Ringer's (LR) prereperfusion to clear K(+)-rich preservation solution from the hepatic vasculature. LR has been shown, however, to be injurious to the graft. By restoring portal blood flow without rinsing and discarding the initial blood traversing the liver (PB flush), we sought to eliminate rinsing without inducing hyperkalemia. Between August 1988 and December 1992, 481 OLTx were performed in 412 pts. Four rinsing methods were used sequentially: group 1 (157 pts)--low-flow-rate cold LR rinse (500 ml, 100 ml/min via standard i.v. tubing at 100 cm H2O [LFLR]) during lower caval anastomosis; Group 2 (120 pts)--LFLR as in group 1, at reperfusion, 500 ml PB flush via IVC catheter; group 3 (66 pts)--high-flow-rate LR rinse (500 ml, 1 L/min using large-bore tubing with 100 cm H2O rinsing pressure [HFLR]), PB flush as in group 2; Group 4 (62 pts)--no LR rinse; PB flush as in groups 2 and 3. Poor early graft function (PEGF) was defined as peak ALT or AST > 2500 U or PT > 16 sec (on POD 2); PEGF causing re-OLTx or death within 14 days was called primary nonfunction (PNF). Group 1 and Group 3 had high PEGF rates. Group 4 had significantly less PEGF than Group 1, with a trend toward a significant difference from Group 3. In Group 1, 3 pts. had intraoperative hyperkalemic cardiac arrest; this did not occur when PB flush was performed. PB flush without prior rinsing optimizes graft function without risk of hyperkalemia. LR rinse, alone or followed by PB flush, is unnecessary and may be deleterious.

Domino liver transplantation from a living related donor.

BACKGROUND: Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. METHODS: The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). RESULTS: The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. CONCLUSION: A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis.

Sensitivity of hepatocellular carcinoma to nine anticancer drugs is unchanged after administration of epirubicin suspended in lipiodol.

Multidrug resistance is a major obstacle to the successful chemotherapy for human cancers. The chemosensitivities of hepatocellular carcinoma (HCC) treated with preoperative lipiodolization (LPD) to anticancer agents were compared to those without chemotherapy. Data on 22 patients with HCC treated with LPD (epirubicin, 20-70 mg/m(2) and lipiodol, 0.05-0.25 ml/kg) prior to hepatectomy (LPD group) and 77 with HCC treated by hepatic resection alone (control group) were compared. Chemosensitivities of resected tissues were tested by succinate dehydrogenase inhibition (SDI) tests for nine anticancer agents, epirubicin, adriamycin, mitomycin-C, cisplatin, carboquone, cyclophosphamide, 5-fluorouracil, etoposide, and vindesine. Among the anticancer agents studied, HCC was most sensitive (38% in the LPD group, 50% in the control) to cyclophosphamide and least sensitive (0% in LPD group, 2% in the control) to etoposide. There was no statistically significant difference in chemosensitivity between the two groups. As HCC does not seem to acquire multidrug resistance after single LPD with epirubicin, repeated LPD with epirubicin can be considered.

Enantioselective intramolecular aromatic [4 + 4] photocycloaddition in crystalline state: parameters for reactivity.

Photoreactivity of seven 9-anthryl-N-(naphthylcarbonyl)carboxamide derivatives, 1a-g, in their intramolecular [4 + 4] photocycloadditions in solid state is discussed on the basis of their single-crystal X-ray analyses. The distances (d(1) and d(2)) between the two carbon atoms to be reacted, the angles (theta(1) and theta(2)), and the torsion angle (theta(3)) between the anthracene and naphthalene rings were chosen as structural parameters for reactivity. For 1a and 1e, the first example of absolute asymmetric synthesis in [4 + 4] photocycloaddition was attained. [reaction: see text]

Partial hepatic grafting: porcine study on critical volume reduction.

BACKGROUND: The safe limit of volume reduction in partial hepatic transplantation, including extracorporeal hepatic resection, remains to be clarified. This study evaluated such a limit and pathologic features associated with transplantation of a less than critical volume. METHODS: Partial hepatic grafting was performed in a porcine orthotopic autotransplantation model. According to the remnant liver volume, animals were classified into three groups: group 1, 73.8% +/- 4.2% (SD); group 2, 52.6% +/- 6.7%; and group 3, 29.4% +/- 6.7% of the whole liver (n = 5 each). RESULTS: Three-day survival was achieved in five (100%), four (80%), and zero animals, respectively. All animals in group 3 died of graft nonfunction; their intraoperative clearance of the total bile acids was significantly worse than the other groups (p < 0.01). After operation the clearance of the total bile acids and hyaluronic acid, which is selectively cleared by hepatic endothelial cells, was significantly better in group 1 than group 2 (p < 0.01 and < 0.05, respectively). On histologic examination postperfusion biopsy specimens of group 3 exhibited severe ischemic changes and portosinusoidal hyperemia, whereas that of groups 1 and 2 exhibited only mild ischemic damages. CONCLUSIONS: Transplantation of less than 30% of expected full liver volume could lead to primary graft nonfunction after partial hepatic grafting.

Extracorporeal hepatic resection for previously unresectable neoplasms.

BACKGROUND: Some hepatic tumors are judged inoperable solely for anatomic reasons, such as the proximity of the tumor with the major vasculature. This is because of high mortality and morbidity rates, as well as a compromised surgical margin. METHODS: We successfully performed extracorporeal hepatic resections in two patients who were judged to have inoperable tumors by conventional means. RESULTS: Both patients had an uneventful postoperative course, and although one patient had intrahepatic recurrence 6 months after operation, the other patient shows no recurrence 10 months later. CONCLUSIONS: Advances in techniques for liver transplantation and organ preservation now allow resection of anatomically unresectable hepatic tumors that were deemed inoperable in the past.

Halothane effects on low-threshold receptive field size of rat spinal dorsal horn neurons appear to be independent of supraspinal modulatory systems.

Recent evidence strongly supports the importance of spinal sites of action for the ability of general anesthetic agents to block response to noxious stimuli. This study was designed to examine possible spinal anesthetic effects on non-noxiously evoked activity. Three groups of rats were prepared for acute experiments in which the response of spinal dorsal horn neurons to low threshold receptive field (RF) stimulation was evaluated. In each animal in each group extracellular activity was recorded from a single spinal dorsal horn neuron. A low-threshold RF of each neuron and, at times, the sensitivity to low-threshold stimulation of multiple sites in the RF were determined under baseline conditions (light anesthesia or decerebrate). In Group 1, reversible cooling of the thoracic spinal cord in the presence of either 0.5% or 1% halothane anesthesia caused no change in RF size. However, an increase from 0.5% to 1% halothane caused a 53% decrease in RF size both in the presence and absence of a reversible cold block of the spinal cord. In Group 2, animals with spinal cords transected at the thoracic level had a similar change in low-threshold receptive field size (52%) when halothane concentrations were increased from 0.5% to 1%. Testing sensitivity within the RF areas indicated that the silenced areas at the fringe of the receptive field could still elicit activation of spinal dorsal horn neurons but at a higher threshold. In the final group of animals, decerebration and spinal cord transection allowed us to compare effects of 0.5% and 1% halothane with an anesthetic free baseline. Here, again, a dose-dependent reduction in RF area was observed although the baseline RFs were significantly smaller than those in Groups 1 and 2. These results demonstrate that the reduction in low-threshold receptive field size due to the administration of the inhalation anesthetic halothane occurs in the absence of descending modulation from supraspinal sites. This implicates the spinal dorsal horn as a potentially important site of action for general anesthetics. These results also support the spinal cord as an important tool to study the pharmacology responsible for anesthetic effects on sensory processing.

Fluorescent pigments by covalent binding of lipid peroxidation by-products to protein and amino acids.

The fluorescent products formed on reaction of 12-oxo-cis-9-octadecenoic acid (12-keto-oleic acid) with about 20 different amino acids, polylysine and bovine serum albumin (BSA) were studied. Besides glycine, only the basic amino acids histidine, lysine and arginine gave products with strong fluorescence. N-Acetylation of amino acids greatly reduced the fluorescence of their reaction products. The formation of fluorescent products was inhibited strongly by SH-amino acids such as N-acetyl-cysteine and glutathione. Polyacrylamide gel electrophoresis showed that BSA treated with 12-keto-oleic acid was more acidic than untreated or ricinoleic acid-treated BSA, indicating that basic amino acid residues in BSA were modified by reaction with the keto fatty acid. None of the structural analogs of 12-keto-oleic acid tested--12-oxo-trans-10-octadecenoic acid, 12-oxo-octadecanoic acid, 12-hydroxy-cis-9-octadecenoic acid (ricinoleic acid), cis-9-octadecenoic acid (oleic acid) and linoleic acid--reacted with glycine to give a fluorescent product. The fluorescent products formed on reaction of 12-keto-oleic acid methyl ester with benzyl amine and glycine methyl ester were shown to be 8-(N-substituted-4,5-dihydro-4-oxo-5-hexyl-5-hydroxy-2-pyrrolyl) octanoic acid methyl esters. The fluorescence properties of these compounds were attributed to the chromophobic system NC = CC = O which contains 6 pi electrons. This investigation contributes to insight of the mechanism of formation of fluorescent pigments, probably by a similar reaction of other compounds of the beta, gamma-unsaturated carbonyl type.

Biliary reconstruction in living donor liver transplantation with dye injection leakage test and without stent use.

Biliary complication remains a significant source of morbidity and mortality in living donor liver transplantation. From October 1996 to December 1999, 34 patients underwent 35 living donor liver transplantations at Kyushu University Hospital. In the initial twenty cases, anastomotic internal stents were placed. In the most recent fifteen cases, no internal stent was inserted and routine postreconstruction dye injection leakage tests were administered. In recipient biliary reconstruction, hepaticojejunostomy was performed using interrupted sutures without an anastomotic stent. After an intestinal clamp was applied at the anal side of the hepaticojejunostomy, leakage test was done using diluted indigocarmine solution injected into the jejunal loop lumen. Two (13%) of the fifteen recent patients suffered from biliary complications, whereas eight patients (40%) from the former twenty patients suffered from biliary complications. We conclude that the use of the stent was not useful, but the application of the dye injection leakage test was useful.

Early detection of recurrent hepatocellular carcinoma.

BACKGROUND/AIMS: Early detection and treatment of recurrent hepatocellular carcinoma (HCC) are keys to patient survival after hepatic resection. In attempts at early detection, we make use of the alpha-fetoprotein (AFP) test every month and abdominal ultrasound (US) and computed tomography (CT) are carried out every three months after hepatectomy. The objective of the present study was to evaluate the most appropriate interval for follow-up re-examinations after resection for HCC. PATIENTS AND METHODS: Eighty-five patients with recurrent HCC were divided into two groups according to the state of the tumor when recurrence was detected: Group I (n = 70); tumor size < or = 2.0 cm, and group II (n = 15); tumor size > or = 2.1 cm. Clinicopathological comparisons were made between the two groups. RESULTS: AFP positivity in group I was significantly lower than group II at the time of recurrence. Rates of extrahepatic intra-abdominal recurrences, i.e. recurrence at the surgical stump and in the abdominal cavity and lymph nodes around the liver, were more frequent in group II than in group I (47% vs 4%; p < 0.001). The average tumor size was larger in 10 patients with extrahepatic intra-abdominal recurrence than in 75 patients with intrahepatic recurrence (3.4 +/- 2.0 vs 1.6 +/- 0.6 cm; p < 0.0001). There was a statistically significant difference regarding the histological grade of initial HCC between the two patterns of recurrence. CONCLUSIONS: Measurements of AFP were seen to have limited value for detecting recurrence, at an early stage. Close postoperative follow-up, including bedside US in the outpatient clinic, should be carried out when the initial HCC is histologically less differentiated HCC.

Empty sella syndrome with visual field disturbance.

Three patients with empty sella syndrome with various visual field disturbances were reported. In one patient there was evidence of enlargement of Mariotte spots, and in the others, irregular visual field defects. These three patients were initially suspected to have intraocular tumors because of the balloonings of the sella and visual field disturbances. However, the diagnosis of empty sella was confirmed by metrizamide cisternography and metrizamide computed tomography(CT). The results indicate that the patient with enlargement of the sella on the plain skull X-ray and visual field disturbance should be examined by metrizamide cisternography and metrizamide CT scan to differentiate from the intrasellar tumor.

[An adult case of basal encephalomeningocele with recurrent meningitis].

A 35-year-old man developed meningitis for the first time at the age of 23. Thereafter, he repeatedly suffered from meningitis for six times before he was admitted to our clinic. Each meningitis was preceded by upper respiratory infection. Chronic infection in the head and neck, fracture of the skull base, liquorrhea, Mollaret meningitis, and acquired immunodeficiency were all ruled out. Nasal fiberscope examination revealed a palpating white tumor in the left olfactory cleavage. Coronal CT scanning demonstrated encephalomeningocele at the left ethmoidal cavity. The encephalomeningocele was surgically repaired and the patient has been free from further meningitis. The causal relationship between the encephalomeningocele and recurrent meningitis was discussed.

[A survey of perioperative bronchospasm in 105 patients with reactive airway disease].

We investigated the relationship between the intra- and postoperative incidence of bronchospasm and the predisposing preoperative factors in 105 patients with reactive airway disease. (1) The incidence of bronchospasm in intra- and postoperative period was not associated with age, sex, duration of bronchial asthma, severity of disease, duration of the anesthesia and operation, or with FEV1.0%. (2) The incidence of intraoperative bronchospasm was high with general anesthesia using endotracheal intubation (8.9%), but low with general anesthesia using mask and regional anesthesia (0% and 2.2%, respectively). (3) The incidence of postoperative bronchospasm was about 20% with both general and regional anesthesia. However, the incidence of postoperative bronchospasm was higher in thoracic and abdominal surgeries than in other surgeries (39.5%:10.4%). (4) The incidences of intra- and postoperative bronchospasm increased in proportion to the proximity of the latest asthmatic attack to the operative date. (5) Prophylactic preoperative inhalation of bronchodilators was effective in the prevention of intraoperative bronchospasm, but some patients developed postoperative wheezing within a few days after the cessation of postoperative inhalation.

[Intrathecal clonidine--how does it work in spinal fentanyl analgesia in rats?].

The effects of intrathecal clonidine on spinal fentanyl analgesia were studied by the hot-plate test (52.0 degrees C) in rats. Clonidine (5 micrograms) and/or fentanyl (5 micrograms) were administered alone or combined in volume of 10 microliters through a chronically-implanted polyethylene catheter (PE-10) whose tip was near the lumbar enlargement of the spinal cord. Injections were done repeatedly every two or three days to determine the time course of thermal analgesia. Results were as follows; 1) Intrathecal clonidine (n = 5) produced no thermal analgesia. 2) Intrathecal fentanyl (n = 10) produced a profound thermal analgesia which was attenuated markedly by the repeated injections in six rats before the 9th injection. 3) Two out of six fentanyl tolerated rats responded with remarkable increases in thermal thresholds following the intrathecal clonidine with fentanyl. 4) Rats which were administered with both clonidine and fentanyl from the 1st injection (n = 9) responded with a extended prolongation of the escape latency, compared with the rats which received fentanyl only. In this group, the tolerance developed in only three animals by the 9th injection. In conclusion, combined intrathecal administration of clonidine with fentanyl potentiated the analgesic effect of fentanyl and then definitely suppressed the tolerance formation even if a small dose of clonidine which produces no analgesic effect was used. These results suggest that intrathecal or epidural administration of clonidine with narcotics might be useful in managing intractable pain.

[Clinical study of patients with hepatic disease at a city hospital in Japan--consideration on indications for liver transplantation].

One-hundred and ninety-one patients with liver diseases who were admitted to National Fukuoka Central hospital during a 3 years period between January 1, 1984 and December 31, 1986 were studied to assess the indications for liver transplantation with the use of a criteria by Dr. Van Thiel et al. The patients were divided into 2 groups; I--indication and II--no indication. Then group I was divided into 3 groups; A--no contraindication, B--relative-contraindication and C--contraindication. Of the 131 patients, group A and B which had the indication of liver transplantation without contraindication were 17%. Deaths by April 30, 1990 were as follows; I 62% (A 36%, B 86%, C 100%) and II 12%. Ten out of 13 deaths in Group I were all due to hepatic failure, while only 3 out of 8 deaths in Group II were due to hepatic failure. Of the other 60 patients with malignancy, 57 were hepatocellular carcinomas, and the other 3 were 2 metastatic hepatic cancers and cholangioma. Among the patients with hepatocellular carcinoma, 24 out of 46 died of cancer, while the other 19 patients died of hepatic failure. The criteria of the indication of liver transplantation seems acceptable for the evaluation of Japanese patients with non-malignant hepatic diseases. As to patients with hepatocellular carcinoma, a new and separate criteria is in need to evaluate them for liver transplantation.