Immunohistochemical study of the muscularis externa of the esophagus in achalasia patients.

The etiology of achalasia is believed to be the neuropathy associated with chronic inflammation of the nerve plexus, but the cause of plexus inflammation is unknown. The purpose of this study was to evaluate the pathophysiology of achalasia by examining the muscularis externa of the esophagus. We used the muscularis externa of the esophagus of 62 patients with achalasia (median 44 years, male : female 32:30) who underwent surgical treatment (achalasia group) and of 10 patients (median 65.5 years, male : female 9:1) who underwent esophagectomy for thoracic esophageal cancer (control group) to perform immunohistochemical staining with S-100, CD43, c-kit (CD117), n-NOS, vasoactive intestinal polypeptide (VIP), and ubiquitin. The cell counts that were positive for S-100, n-NOS, VIP, and ubiquitin were significantly lower in the achalasia group compared with the control group (P < 0.001, P= 0.001, P < 0.001, and P= 0.001, respectively). There were no statistically significant differences with respect to CD43 and c-kit staining (P= 0.586 and P= 0.209, respectively). In conclusion, the pathophysiology of achalasia is therefore considered to be an impaired production of NO and VIP, which both affect interstitial cell of Cajal and smooth muscles, and this impairment is therefore considered to play a role in the pathophysiology of achalasia.

Single-blind randomized clinical trial of transinguinal preperitoneal repair using self-expanding mesh patch vs. Lichtenstein repair for adult male patients with primary unilateral inguinal hernia.

PURPOSE: The aim of the study was to compare proportions of chronic postoperative inguinal pain (CPIP) and other surgical outcomes between transinguinal preperitoneal repair with modified Kugel patch (MK) and Lichtenstein repair (LR). METHODS: Two-hundred adult male patients with primary unilateral inguinal hernia were randomized into MK or LR groups. The primary endpoint was CPIP, pain at 6 months after surgery. Secondary outcomes included recurrence rate, incidence of postoperative complications, time until return to activities, inguinal pain and sensory disturbances assessed at 1 week, 1 month, 3, 6, and 12 months after the operation using an 11-point numerical rating scale (NRS). The study was an intention-to-treat analysis. RESULTS: In comparison of MK (n = 100) and LR (n = 100) with similar backgrounds, proportions of CPIP were similar (7.2 vs. 11.1%, p = 0.3452). Favorable outcomes for MK were duration of operation (32 vs. 40 min, p < 0.0001), NRS of foreign body sensation at 1 year (0 [0-1] vs. 0 [0-2], p = 0.0067), and NRS of numbness at 1 month (0 [0-1] vs. 0 [0-3], p = 0.0078) after the operation. CONCLUSIONS: In regard to CPIP, the short-term results of MK and LR were similar.

A phase I study of full-dose gemcitabine and regional arterial infusion of nafamostat mesilate for advanced pancreatic cancer.

BACKGROUND: The primary end points of this study were to determine the dose-limiting toxic effects (DLTs), maximum tolerated dose, and a recommended phase II dose of a synthetic serine protease inhibitor, nafamostat mesilate, in combination with full-dose gemcitabine in patients with unresectable locally advanced or metastatic pancreatic cancer. The secondary end point was to assess therapeutic response. PATIENTS AND METHODS: Patients with previously untreated pancreatic cancer received gemcitabine (1 000 mg/m(2) i.v. for 30 min) on days 1, 8, and 15, with nafamostat mesilate (continuous regional arterial infusion for 24 h through a port-catheter system) on days 1, 8, and 15; this regimen was repeated at 28-day intervals. The initial dose of nafamostat mesilate was 2.4 mg/kg and was escalated in increments of 1.2 mg/kg until a dose of 4.8 mg/kg was achieved. A standard '3+3' phase I dose-escalation design was used. Therapeutic response and clinical benefit response were assessed. RESULTS: Twelve patients were enrolled in this study. None of the patients experienced DLTs, and nafamostat mesilate was well tolerated at doses up to 4.8 mg/kg in combination with full-dose gemcitabine. This combination chemotherapy yielded a reduction of a high serum level of the tumor marker CA19-9. Pain was reduced in three of seven patients without oral morphine sulfate. Overall survival was 7.1 months for all patients. CONCLUSION: This phase I study was carried out safely. This combination chemotherapy showed beneficial improvement in health-related quality of life. The recommended phase II dose of nafamostat mesilate in combination with full-dose gemcitabine is 4.8 mg/kg.

Eradication of Helicobacter pylori in a Living Donor Liver Transplant Recipient With Immunosuppressive Therapy of Cyclosporine A: A Case Report.

A 54-year-old woman underwent living donor liver transplantation (LDLT) for primary biliary cholangitis (PBC) three years earlier. She took cyclosporine A (CyA) 150 mg/day as immunosuppression for prevention of rejection and PBC recurrence. Routine upper gastrointestinal endoscopy showed chronic atrophic gastritis and hyperplastic polyp, and rapid urease test was positive. Anti-Helicobacter pylori (H. pylori) serum IgG was elevated to 51 U/ml. We performed H. pylori eradication therapy with amoxicillin, clarithromycin and lansoprazole measuring the blood CyA concentration every day. Although the blood CyA concentration reached a peak (the concentration 2 hours after the administration: 818 ng/ml) on the second day, she did not develop renal dysfunction or other obvious adverse effects. Five weeks after the treatment, we confirmed eradication of H. pylori with the urea breath test. We herein reported a case of successful eradication of H. pylori in a LDLT recipient on immunosuppressive therapy with CyA without adverse effects.

The significance of the aberrant left hepatic artery arising from the left gastric artery at curative gastrectomy for gastric cancer.

BACKGROUND: An aberrant left hepatic artery (ALHA) is occasionally encountered during esophagogastric surgery. However, at curative gastrectomy for gastric cancer, it is questionable as to whether the ALHA need to be divided in order to maximize lymph node clearance and the issue requires clarification. METHODS: We encountered 50 patients with an ALHA during curative gastrectomy for gastric cancer between 1997 and 2001. Data concerning operative feasibility, postoperative liver function and therapeutic value of nodal dissection were analyzed retrospectively. RESULTS: For 27 patients, we preserved the ALHA, and for the remaining 23 patients, we divided the ALHA at the origin of the left gastric artery (LGA). Serum levels of aspartate aminotransferase and alanine aminotransferase were statistically significant higher on postoperative day (POD) 1 (P=0.0008 and P=0.0007), and on POD 3 (P=0.001 and P=0.008), respectively, in the ALHA-divided group. Patients who underwent a total gastrectomy predominated in the ALHA-divided group, the total number of dissected lymph nodes being higher in the ALHA-divided group (P=0.018). However, the total numbers of dissected lymph nodes and metastatic lymph nodes around the LGA were similar in the 2 groups (P=0.447 and P=0.128), respectively. No significant differences were seen between the 2 groups in morbidity and mortality. The overall 5-year survival rates were also comparable. CONCLUSIONS: Although a prospective study is required, this study suggested that routine division of the ALHA may not always be required for curative gastrectomy.

Prediction of recurrence after laparoscopic fundoplication for erosive reflux esophagitis based on anatomy-function-pathology (AFP) classification.

BACKGROUND: The usefulness of the anatomy-function-pathology (AFP) score was examined to evaluate its prediction of recurrence after laparoscopic fundoplication for erosive reflux esophagitis. METHODS: Of the patients undergoing laparoscopic fundoplication for erosive reflux esophagitis of Los Angeles classification grade A or higher from December 1994 to December 2004, 107 who underwent preoperative barium esophagogram, pH monitoring, and endoscopy were selected as subjects. The AFP score was calculated by A, F, and P factor grades of the AFP classification. By comparing patients with and without recurrence, the usefulness of the AFP score for predicting recurrence was examined. RESULTS: Reflux esophagitis recurred in seven patients. No significant difference in age, sex, or A or F factor was observed between the groups, whereas a significant difference was observed in the P factor (p = 0.008). On the other hand, the mean AFP score in the recurrence group was 16.9 +/- 5.3, whereas that in the nonrecurrence group was 8.9 +/- 5.3 (p = 0.0021). Among the patients with a score of 17 points or more (n = 23), recurrence was found in 6 patients (26%). On the other hand, among the patients with a score lower than 17 points (n = 84), recurrence was found in 1 patient, but not in the remaining 83 patients (1%). Sensitivity was thus 85.7% (95% confidence interval [CI], 42.1-99.6), and specificity was 83% (95% CI, 74.2-89.8). The positive predictive value was 26.1% (95% CI, 10.2-48.4), and the negative predictive value was 98.8% (95% CI, 93.5-99.9). Multiple logistic regression analysis was performed, and receiver operating characteristics curves were obtained. The area under the curve for the AFP score was 0.8457, whereas that for the P factor was 0.7907 (p = 0.0045), suggesting that the AFP score may more accurately predict recurrence than the P factor. CONCLUSION: The AFP score may be useful for predicting postoperative recurrence. If surgery is performed when the AFP score is lower than 17 points, the likelihood of postoperative recurrence is expected to be very low.

Usefulness of chemoradiotherapy for inoperable gastric cancer.

Introduction Radiotherapy is not commonly used for the treatment of gastric cancer in Japan, where surgery is the standard local treatment. We report the results of chemoradiotherapy in patients with advanced or recurrent gastric cancer which was deemed difficult to treat surgically. Methods Twenty-one patients with gastric cancer (including sixteen with advanced/recurrent gastric cancer and five with poor general condition) underwent chemo-radiotherapy, for whom the therapeutic efficacy, toxicity and survival period were analysed. Results The tumour response to chemoradiotherapy was categorised as complete, partial, stable or progressive in 5, 9, 3, and 4 patients, respectively, with an overall response rate of 67%. No serious complications such as gastrointestinal perforation or bleeding occurred, and no cardiac, hepatic or renal dysfunction developed during the follow-up period. The mean survival time was 19.8 months (range, 3-51 months). One patient died of another disease, 18 died of primary cancer and the cause of death was unknown in 2 patients. Conclusions Chemoradiotherapy appears to be an effective treatment for localised gastric cancer without distant metastases, but further studies are needed to determine the indications for chemoradiotherapy and late adverse effects, as well as the chemotherapy regimens to be used.

Significance of Portal Venous Velocity in Short-term Graft Function in Living Donor Liver Transplantation.

BACKGROUND: Graft regeneration and functional recovery after reperfusion of transplanted graft are very important for successful living donor liver transplantation (LDLT). The aim of this study was to evaluate the significance of postoperative portal venous velocity (PVV) in short-term recovery of graft function in LDLT. PATIENTS AND METHODS: From February 2007 through December 2015, we performed 17 primary LDLTs, which were included in the present study. The patients ranged in age from 12 to 65 years (mean: 50 years), and 11 were female patients. Postoperatively, Doppler ultrasonography was performed daily to measure PVV (cm/s), and liver function parameters were measured daily. The change in PVV (ΔPVV) was defined as follows: ΔPVV = PVV on postoperative day (POD) 1 - PVV on POD 7. Maximal value of serum aspartate aminotransferase (ASTmax) and maximal value of serum alanine transaminase (ALTmax) at 24 hours after graft reperfusion were used as parameters of reperfusion injury. Correlation analyses were performed as follows: (1) correlation of ΔPVV and PVV on POD 1 (PVV-POD 1) with the values such as ASTmax, ALTmax, other liver function parameters on POD 7 and graft regeneration rate; (2) correlation of ASTmax and ALTmax with other liver function parameters on POD 7. RESULTS: ΔPVV significantly correlated with the values of serum total bilirubin (P < .01), prothrombin time (P < .01), and platelet count (P < .05), and PVV-POD 1 significantly correlated with the values of serum total bilirubin (P < .05) and prothrombin time (P < .05). CONCLUSION: ΔPVV and PVV-POD 1 may be useful parameters of short-term functional recovery of the transplant liver in LDLT.

Successful Treatment of Stricture of Duct-to-Duct Biliary Anastomosis After Living-Donor Liver Transplantation of the Left Lobe: A Case Report.

Biliary complications, such as stricture or obstruction, after living-donor liver transplantation (LDLT) remain major problems to be solved. Magnetic compression anastomosis (MCA) is a minimally invasive method of biliary anastomosis without surgery in patients with biliary stricture or obstruction. A 66-year-old woman had undergone LDLT for end-stage liver disease for primary biliary cholangitis 20 months previously at another hospital. Computerized tomography showed dilation of the intrahepatic bile duct (B2). Because B2 was invisible with the use of endoscopic retrograde cholangiopancreatography, percutaneous transhepatic biliary drainage (PTBD) was performed for treatment of cholangitis. The rendezvous technique failed because a guidewire could not pass through the biliary stricture. Therefore, we decided to perform MCA. A parent magnet was endoscopically placed distally in the common bile duct of the stricture, and a daughter magnet attached to a guidewire was inserted proximally through the fistula tract of the PTBD. Both magnets were positioned across the stricture, and the 2 magnets were pulled to each other by magnetic power, to sandwich the stricture. By 14 days after MCA, a fistula between B2 and the common bile duct was created. At 28 days after MCA, the magnets were removed distally and a 16-French tube was placed across the fistula. At 7 months after MCA, that tube was removed. In conclusion, when a conventional endoscopic or percutaneous approach including the rendezvous technique fails, MCA is a good technique for biliary stricture after LDLT.

Familial clustering in subgroups of gastric cancer stratified by histology, age group and location.

AIM: To assess the risk of gastric cancer in a Japanese patient population with the disease by stratification with histology, age, tumour location and the association with family history of gastric or non-gastric tumours. METHODS: A retrospective analysis of 1400 consecutive patients with gastric cancer and 13,467 age- and gender-matched controls from a pre-recorded database using conditional logistic regression models. RESULTS: Young patients (< or = 43 years of age) with gastric cancer of intestinal type had a strong association with family history of gastric cancer in first degree-relatives (OR=12.5). Moreover, when a history of gastric cancer was observed in both parents, there was an increased risk of gastric cancer intestinal type (OR=7.8), more commonly in the proximal and mid-stomach. In contrast, there was an increased risk of diffuse-type cancer when both parents suffered non-gastric cancers (OR=2.1). CONCLUSION: These data suggest that the degree of familial clustering differ in gastric cancer subgroups stratified by histology, age, and stomach location in this Japanese population.

Laparoscopic Heller myotomy and Dor fundoplication for the treatment of achalasia. Assessment in relation to morphologic type.

BACKGROUND: The significance of laparoscopic Heller myotomy and Dor fundoplication (LHD) for the treatment of achalasia in relation to the severity of the lesion has not been sufficiently assessed. METHODS: Of patients who were diagnosed with achalasia from August 1994 to February 2004, 55 individuals who underwent LHD served as subjects. The therapeutic effects of LHD were assessed in terms of operation time, intraoperative complications, postoperative hospital stay, and symptom improvement in relation to morphologic type (spindle type, Sp; flask type, Fk; and sigmoid type, Sig). Degree of symptomatic improvement was classified into four grades: excellent, good, fair, and poor. RESULTS: Breakdown of morphologic type was as follows: Sp, n = 29; Fk, n = 18; and Sig, n = 8. Excluding one patient for whom conversion to open surgery was required, median average operation time for 54 patients was 160 min. As to intraoperative complications, esophageal mucosal perforation was seen in nine of the 55 patients (16%); however, conversion to open surgery could be avoided by suturing the affected area. Moreover, intraoperative bleeding of at least 100 g was seen in five of the 55 patients (9%), with one Fk patient requiring conversion to open surgery and transfusion. Median postoperative hospital stay was 8 days. Degree of dysphagia relief was excellent in 45 patients (83%), good in eight patients (15%), and fair in one patient (2%). Excellent improvement was obtained in 90%, 88%, and 50% in Sp, Fk, and Sig patients, respectively. Reflux esophagitis was seen in two patients, and was treated with a proton pump inhibitor. CONCLUSIONS: The results of the present study suggest that classification of morphologic type is a useful parameter in predicting postoperative outcome in achalasia. In order to achieve excellent symptomatic relief, surgery for achalasia should be recommended for but not limited to Sp and Fk types.

Hand-assisted laparoscopic and thoracoscopic surgery (HALTS) in radical esophagectomy with three-field lymphadenectomy for thoracic esophageal cancer.

AIM: To prove the feasibility of hand-assisted laparoscopic and thoracoscopic surgery (HALTS) for radical esophagectomy with three-field lymphadenectomy to thoracic esophageal cancer. METHODS: Esophagectomy with three-field lymphadenectomy was performed using HALTS in 19 patients with thoracic esophageal cancer without distant metastasis. Five patients had chemo-radiotherapy prior to surgery. RESULTS: All operations were completed successfully without the need for open surgery. Mean surgical time was 476+/-58 min, and mean blood loss during surgery was 343+/-184 mL. All patients started tube feeding and were moved from the intensive care unit to the general surgery ward the day after surgery. Discharge occurred a median of 10 days after surgery. Fifteen patients could return to full time jobs from 8 to 62 days after surgery (median 22 days) and from 1 to 35 days after discharge (median 9 days). Other three could return to daily activities at home soon as well. No major complications occurred, except one anastomotic leak. In terms of lung function, %FEV(1) was not changed whereas %VC was reduced significantly 1 month after surgery. All but two recurrences have been healthy without a relapse for a mean of 289 days. CONCLUSIONS: These results suggest that HALTS may be a useful surgical technique to reduce the invasiveness of conventional radical esophagectomy with three-field lymphadenectomy for thoracic esophageal cancer.

Characteristics of hepatocytes derived from early ES cells and treatment of surgically induced liver failure rats by transplantation.

BACKGROUND: Although liver transplantation has become a standard therapy for diseases such as fulminant hepatitis and cirrhosis, the lack of donor organs remains a major problem. One solution is the development of transplantable hepatocytes. The metabolic characteristics as well as function and adaptation of hepatocytes (R-EES-hep cell) derived from rat early embryonic stem cells were examined after transplantation into rats with surgically induced liver failure. METHODS: Rat hepatocyte cell lines were established from early embryonic stem cells cultured in the presence of embryotrophic factors by colony cloning methods. The cell lines were established from two cell embryos taken from spontaneous dwarf rats using the novel method of Ishiwata et al. Morphologic differentiation as well as albumin and bilirubin production were observed by immunostaining. R-EES-hep cells were transplanted into the spleens of 90% hepatectomized, surgically induced liver failure rats to analyze survival rates. RESULTS: When cultured in type I collagen gel the cells formed cordlike structures resembling the liver. Both albumin and bilirubin production were observed when transplanted; the spleen was converted into a liver-like structure with prolonged survival of the 90% hepatectomized rats for up to 3 months up to the time of killing. CONCLUSIONS: R-EES-hep cells showed many of the distinctive metabolic characteristics of the liver. These cells may be efficient for further research and application for hepatic cell transplantation to treat liver insufficiency patients and as biologic artificial organs.

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.

Hemodynamic and biochemical changes during normothermic and hypothermic sanguinous perfusion of the porcine hepatic graft.

Using an ex vivo liver sanguinous perfusion system, hemodynamic and biochemical changes of the porcine livers were studied, which were preserved cold (4 degrees C) for 24 hr in University of Wisconsin solution and reperfused with normothermic (37 degrees C) (n = 8) or hypothermic (32 degrees C) (n = 8) blood for 3 hr. Six more livers were reperfused with normothermic blood (37 degrees C) immediately after procurement as controls. The total hepatic blood flow was adjusted to 1 ml/min/g liver weight, in which hepatic artery and portal vein flows were administered at a 1:2 ratio. In livers stored cold for 24 hr in UW solution and perfused normothermically, a statistically higher hepatic artery resistance was exhibited at 30 and 60 min after reperfusion (P less than 0.05), and there was lower bile output (P less than 0.05) at 90 and 120 min as compared to the controls. In livers stored cold for 24 hr in UW solution and perfused hypothermically, as compared to ones perfused normothermically, statistically higher hepatic-artery and portal-vein resistances (P less than 0.05) were observed throughout the perfusion period and 60 min after reperfusion, respectively. In addition, bile output and oxygen consumption of these livers were statistically lower than those of ones perfused normothermically (P less than 0.05). In contrast, chemistries of the perfusate of livers perfused hypothermically were comparable to ones perfused normothermically. Histologic examination of the liver perfused hypothermically demonstrated hepatic arterial and/or portal venous congestion and mild-to-moderate hemorrhage in the portal triads. This study suggests that livers preserved for a prolonged period of time demonstrate a high hepatic arterial resistance shortly after revascularization, and that recipient hypothermia after revascularization may be a risk factor for the development of hepatic arterial thrombosis following liver transplantation.

Effects of deletion variant of hepatocyte growth factor on reduced-size liver transplantation in rats.

BACKGROUND: The deletion variant of hepatocyte growth factor (dHGF) exerts mitogenic and antifibrotic effects. The purpose of this study was to evaluate the effect of dHGF on rats that had undergone syngeneic or allogeneic reduced-size (60%) orthotopic liver transplantation (ROLT). METHODS: Starting immediately after the syngeneic (Lewis to Lewis) and allogeneic (Lewis to Brown Norway) ROLT, 500 microg/kg dHGF was administered i.v. twice a day until the day the rats were killed. Its effect on hepatic graft weight, regeneration, and biochemical parameters was evaluated. RESULTS: dHGF promoted restoration of the liver volume and liver regeneration as well as protein synthesis in the rats that underwent syngeneic ROLT. In the rats that underwent allogeneic ROLT, dHGF reduced the level of serum cytosolic enzymes related to acute cellular rejection, but a significant improvement in liver regeneration and protein synthesis was not seen. When tacrolimus was administered to prevent rejection of the allogeneic grafts, the beneficial effect of dHGF was apparent, and was as beneficial as in syngeneic ROLT. CONCLUSIONS: Administering dHGF after liver transplantation augments the regeneration and functional recovery of partial liver grafts and reduces hepatocyte injury in acute cellular rejection.

Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation.

BACKGROUND: Proinflammatory cytokines such as interleukin 1-beta (IL-1beta) and tumor necrosis factor-a (TNF-alpha) play an important role in the development of hepatic ischemia/reperfusion injury. FR167653 has been characterized as a potent suppressant of IL-1beta and TNF-alpha production. The aim of this study was to evaluate the effect of FR167653 on cold ischemia/ reperfusion injury in rat liver transplantation. METHODS: Donor livers were preserved with cold University of Wisconsin solution for 48 hr and transplanted orthotopically. Immediately after reperfusion, FR167653 (1 mg/kg, FR-treated group) or normal saline solution (control group) was administered i.v.. The severity of liver injury was determined by hepatic enzyme levels as well as by histological findings. The accumulation of IL-1beta and TNF-alpha mRNA in the liver was analyzed by semi-quantitative reverse transcription-polymerase chain reaction. Tissue factor expression was subjected to immunohistochemical analysis. RESULTS: In the FR-treated group, release of aspartate aminotransferase and alanine aminotransferase after reperfusion was significantly lower (P<0.05 and P<0.02, respectively), and histological liver injury was less prominent, than in the control group. Accumulation of IL-1beta and TNF-alpha mRNA was suppressed in the FR-treated liver. Tissue factor expression on Kupffer cells and sinusoidal endothelial cells, marked in the control group, was almost absent in the FR-treated group. Seven-day survival in the FR-treated group (75%) was significantly better than that in the control group (12.5%) (P<0.01). CONCLUSIONS: These results indicate that treatment with FR167653 ameliorates cold ischemia/reperfusion injury in liver transplantation.

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.

Significance of lecithin:cholesterol acyltransferase activity as a prognostic indicator of early allograft function in clinical liver transplantation.

Rapid and accurate assessment of allograft function in the early postoperative period is critical for successful liver transplantation. This study evaluated the efficacy of lecithin:cholesterol acyltransferase (LCAT) activity as an indicator of early allograft function in human orthotopic liver transplantation (OLTx). During a three-month period between September and November 1987, 9 of 11 adult OLTx recipients whose graft exhibited poor function were studied. Poor graft function was defined as primary nonfunction, need for retransplantation within a week after OLTx, or elevation of the prothrombin time over 20 sec early after OLTx. Plasma LCAT activities (measured pretransplant and at 0, 6, 12, 18, and 24 hr, as well as 3 days, after OLTx) and pretransplant clinical variables were compared with those of 15 control patients whose graft exhibited good function. A significant correlation was found between mean LCAT activities during the first 24-hr after OLTx and early allograft function (P less than 0.05, chi 2 = 5.23). When pretransplant histological findings of the 6 grafts with poor function and the 15 controls together were correlated with the mean LCAT activity within 24 hr following OLTx, a significant association was demonstrated (P less than 0.05). This study suggests that plasma LCAT activity is an effective and practical method for assessing early allograft function following OLTx.

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.