Laparoscopy-assisted spleen-preserving pancreatic resection for epidermoid cyst in an intrapancreatic accessory spleen.

A rare case of an epidermoid cyst originating in an intrapancreatic accessory spleen in a 50-year-old Japanese female is reported. A hypoechoic cystic tumor was detected incidentally by abdominal ultrasonography. It appeared to be a single cyst in the pancreatic tail with a contrasted mass lesion beside it. Laparoscopy-assisted spleen-preserving pancreatic tail resection was performed. Microscopic examination revealed that the cyst was surrounded by fibrous tissue and a thin layer of splenic tissue, adjacent to normal pancreatic parenchyma. The inner surface of the cyst was lined with non-keratinizing squamous epithelium. The diagnosis of an epidermoid cyst occurring in an intrapancreatic accessory spleen was confirmed. Laparoscopy-assisted spleen-preserving pancreatic resection is a safe and effective procedure for benign or low-grade malignant cystic diseases in the pancreas.

Attenuation of liver and lung injury after hepatic ischemia and reperfusion by a cytokine-suppressive agent, FR167653.

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is an important clinical problem and leads to the release of the proinflammatory cytokines, TNF-alpha and IL-1. These cytokines play important roles in the induction of polymorphonuclear neutrophil (PMN) activation and infiltration, and induce not only localized hepatic injury but also remote organ injury, especially pulmonary injury. Using a total hepatic ischemia model in rats, we tested our hypothesis that suppression of TNF-alpha and IL-1 by FR167653 ameliorates I/R injury in the liver and lung. METHODS: Male Wistar rats, weighing 240-280 g, were divided into 3 groups, an FR group, a control group and a sham group. In the FR group, FR167653 (1 mg/kg/h) was administered continuously to the animals for 30 min prior to the onset of ischemia and for 2 h after reperfusion. The control group received normal saline. A porto-systemic shunt was placed between the cecal branch of the portal vein and the jugular vein, and total hepatic ischemia was produced for 90 min. The sham group was treated with placement of the porto-systemic shunt only. The 1-week survival rate, liver enzyme activity, hepatic tissue blood flow (HTBF), cytokine mRNA expression, myeloperoxidase (MPO) activity and histological results were studied. RESULTS: The 1-week survival rate and HTBF were significantly higher in the FR group than in the control group. Serum AST, ALT, and LDH levels were significantly lower in the FR group at 30 min, 1 h and 3 h after reperfusion. MPO levels in liver and lung tissue were also significantly lower in the FR group. The expression of IL-1beta mRNA remarkably decreased up to 6 h after reperfusion in the FR group. CONCLUSIONS: We concluded that the inflammatory cytokines, IL-1beta, play important roles in hepatic I/R injury. FR167653 might ameliorate I/R injury and be useful in liver surgery with ischemia.

Influence of donor cardiopulmonary arrest in human liver transplantation: possible role of ischemic preconditioning.

Hepatic allografts from donors who have suffered a brief cardiopulmonary arrest may sustain ischemic damage before organ procurement. However, there is no reported correlation between donor cardiopulmonary arrest and hepatic allograft dysfunction. On the other hand, brief ischemia-reperfusion injury has been shown experimentally to result in protection in several organ models. Induction of ischemic tolerance has been called ischemic preconditioning. Our objective was to study the influence of brief donor cardiopulmonary arrest on hepatic allograft outcome in human liver transplantation. Between May 1997 and July 1998, 181 consecutive orthotopic liver transplant (OLT) cases were divided into 2 groups based on the occurrence of donor cardiopulmonary arrest. Group A consisted of 37 donors who suffered a cardiopulmonary arrest. Group B consisted of the remaining 144 patients. Liver graft survival within 90 days of OLT and early postoperative graft function were analyzed. Although there was significant liver damage resulting from circulatory failure during cardiopulmonary arrest before organ procurement in group A, graft survival was not affected. After OLT, the mean peak aspartate transaminase and alanine transaminase concentrations in group A (1, 444.1 and 718.2 U/L) were significantly lower than those in group B (2,382.8 and 1,507.3 U/L) (P <.05). Experiences of brief cardiopulmonary arrest in organ donors did not affect post-OLT hepatic allograft survival and function. Although the liver function tests are elevated in an organ donor, the hepatic allograft is suitable for OLT if the liver damage is induced by brief donor cardiopulmonary arrest.

Experimental evaluation of the effects of the intraportal administration of cyclic guanosine monophosphate on ischemia/reperfusion in the porcine liver.

This study was done to examine the protective effects of cyclic guanosine monophosphate (cGMP), a second messenger of nitric oxide, for ischemia/reperfusion injury of the liver, since it is known to induce vasodilatation and to inhibit platelet aggregation. Using an experimental model of porcine liver ischemia, 8-bromoguanosine 3',5' monophosphate, a cGMP analog, was continuously administered into the portal vein before ischemia and after reperfusion 30 min for each in the cGMP group (n = 6). Saline water was administered in the same way in the control group (n = 6). The cardiac output (CO), mean arterial blood pressure (MAP), portal venous flow (PVF), hepatic arterial flow (HAF), hepatic tissue blood flow (HTBF), and hepatic tissue cGMP level were determined. Hepatic enzymes and the bile discharge were also assessed as indicators of hepatic function. The hepatic tissue cGMP level was significantly higher, and PVF, HTBF, and the bile discharge were significantly greater in the cGMP group, while there were no remarkable differences between the groups with CO, MAP, HAF, and hepatic enzymes. In conclusion, the continuous supplementation of cGMP into the portal vein was found to be beneficial for preserving both the hepatic circulation and, consequently, the hepatic function after warm ischemia of porcine liver.

Influence of high donor serum sodium levels on early postoperative graft function in human liver transplantation: effect of correction of donor hypernatremia.

Donor hypernatremia was reported to cause postoperative graft dysfunction in human orthotopic liver transplantation (OLT). However, the effects of the correction of donor hypernatremia before organ procurement have not been confirmed. The aim of this study is to determine whether donor hypernatremia is associated with early graft dysfunction after OLT and to determine the effect of the correction of donor hypernatremia. One hundred eighty-one consecutive OLTs performed between May 1997 and July 1998 were entered onto this study. The cases were divided into three groups according to the donor serum sodium concentration: group A, serum sodium of 155 mEq/L or less before organ procurement (n = 118); group B, peak sodium greater than 155 mEq/L and final sodium 155 mEq/L or less (n = 36); and group C, final sodium greater than 155 mEq/L (n = 27). Graft survival within 90 days after OLT and early postoperative graft function were analyzed. There were no significant differences in donor and recipient variables among the three groups. The frequencies of graft loss were 15 of 118 grafts (12.7%) in group A, 4 of 36 grafts (11.1%) in group B, and 9 of 27 grafts (33.3%; P <.05 v groups A and B) in group C. The liver enzyme values in groups B and C were significantly greater than those in group A postoperatively. The prothrombin times of group C were significantly longer than those of group A for the first 4 postoperative days. Recipients of hepatic allografts from donors with uncorrected hypernatremia had a significantly greater incidence of graft loss compared with recipients of hepatic allografts from normonatremic donors. However, the differences in graft survival were abrogated by the correction of donor hypernatremia before procurement.

Protective role of nitric oxide in ischemia and reperfusion injury of the liver.

BACKGROUND: The suppressed production of nitric oxide (NO), associated with endothelial dysfunction, is thought to be a cause of ischemia and reperfusion injury of the liver. But findings of the salutary effects of NO enhancement on such injury have been conflicting. In this study, we tested our hypothesis that NO enhancement would attenuate ischemic liver injury. For this purpose, an NO precursor, L-arginine, and a novel NO donor, FK409, were applied to a 2-hour total hepatic vascular exclusion model in dogs. STUDY DESIGN: L-arginine was administered IV at a dose of 100 mg/kg twice (n = 5), while 300 mg/kg twice of FK409 was infused continuously into the portal vein (n = 5). The drugs were given to the animals for 30 and 60 minutes before and after ischemia, respectively. Non-treated animals were used as the control (n = 10). Two-week survival, systemic and hepatic hemodynamics indices, liver function tests, energy metabolism, and histopathology were analyzed. RESULTS: Both treatments comparably augmented hepatic tissue blood flow, decreased liver enzyme release, and increased high-energy phosphate restoration during the reperfusion period, all of which contributed to rescuing all of the treated animals from the 2-hour total hepatic ischemia. In contrast, ischemia caused 70% mortality in the control group. Histologically, structural abnormality and neutrophil infiltration were markedly attenuated by the treatments. Systemic hypotension was observed in the animals treated with FK409, however. CONCLUSIONS: Our data demonstrate that NO enhancement alleviates the liver injury caused by ischemia and reperfusion. The supplementation of L-arginine, rather than FK409, is considered more applicable to clinical use because of the absence of systemic adverse effects.

Attenuation of ischemic liver injury by prostaglandin E1 analogue, misoprostol, and prostaglandin I2 analogue, OP-41483.

BACKGROUND: Prostaglandin has been reported to have protective effects against liver injury. Use of this agent in clinical settings, however, is limited because of drug-related side effects. This study investigated whether misoprostol, prostaglandin E1 analogue, and OP-41483, prostaglandin I2 analogue, which have fewer adverse effects with a longer half-life, attenuate ischemic liver damage. STUDY DESIGN: Thirty beagle dogs underwent 2 hours of hepatic vascular exclusion using venovenous bypass. Misoprostol was administered intravenously for 30 minutes before ischemia and for 3 hours after reperfusion. OP-41483 was administered intraportally for 30 minutes before ischemia (2 microg/kg/min) and for 3 hours after reperfusion (0.5 microg/kg/min). Animals were divided into five groups: untreated control group (n=10); high-dose misoprostol (total 100 microg/kg) group (MP-H, n=5); middle-dose misoprostol (50 microg/kg) group (MP-M, n=5); low-dose misoprostol (25 microg/kg) group (MP-L, n=5); and OP-41483 group (OP, n=5). Animal survival, hepatic tissue blood flow (HTBF), liver function, and histology were analyzed. RESULTS: Two-week animal survival rates were 30% in control, 60% in MP-H, 100% in MP-M, 80% in MP-L, and 100% in OP. The treatments with prostaglandin analogues improved HTBF, and attenuated liver enzyme release, adenine nucleotrides degradation, and histologic abnormalities. In contrast to the MP-H animals that exhibited unstable cardiovascular systems, the MP-M, MP-L, and OP animals experienced only transient hypotension. CONCLUSIONS: These results indicate that misoprostol and OP-41483 prevent ischemic liver damage, although careful dose adjustment of misoprostol is required to obtain the best protection with minimal side effects.

Attenuation of ischemic liver injury by monoclonal anti-endothelin antibody, AwETN40.

BACKGROUND: Enhanced production of endothelin-1 (ET-1), vasoconstrictive 21 amino acids produced by endothelial cells during ischemia and after reperfusion of the liver, is known to cause sinusoidal constriction and microcirculatory disturbances, which lead to severe tissue damage. Using a 2-hour hepatic vascular exclusion model in dogs, we tested our hypothesis that neutralization of ET-1 by monoclonal anti-ET-1 and anti-ET-2 antibody (AwETN40) abates vascular dysfunction and ameliorates ischemia/reperfusion injury of the liver. STUDY DESIGN: After skeletonization, the liver was made totally ischemic by cross-clamping the portal vein, the hepatic artery, and the vena cava (above and below the liver). Veno-venous bypass was used to decompress splanchnic and inferior systemic congestion. AwETN40, 5 mg/kg, was administered intravenously 10 minutes before ischemia (treatment group, n = 5). Nontreated animals were used as controls (control group, n = 10). Animal survival, hepatic tissue blood flow, liver function tests, total bile acid, high-energy phosphate, ET-1 levels, and liver histopathology were studied. RESULTS: Treatment with AwETN40 improved 2-week animal survival from 30% to 100%. Hepatic tissue blood flow after reperfusion was significantly higher in the treatment group. The treatment significantly attenuated liver enzyme release, total bile acid, and changes in adenine nucleotides. Immunoreactive ET-1 levels in the hepatic venous blood of the control group showed a significant increase and remained high for up to 24 hours after reperfusion. Histopathologic alterations were significantly lessened in the treatment group. CONCLUSIONS: These results indicate that ET-1 is involved in ischemia/reperfusion injury of the liver, which can be ameliorated by the monoclonal anti-ET-1 and anti-ET-2 antibody AwETN40.

Endothelin-1 levels in portal venous blood in relation to hepatic tissue microcirculation disturbance and hepatic cell injury after ischemia/reperfusion.

This study was conducted to clarify the role of endothelin-1 in the portal vein after hepatic ischemia/ reperfusion and to ascertain whether it is related to hepatic microcirculation disturbance. Using a canine ischemic liver model, the portal and systemic endothelin-1 levels were measured before ischemia, then after 1 h and 2 h of reperfusion, and comparatively evaluated with the serum levels of GOT and lactic dehydrogenase (LDH). As an indicator of liver tissue microcirculation, tissue blood flow volume (TBF) was also measured in the site subjected to ischemia. The animals were divided into: group 1, which received ischemia for 30 min; group 2, which received ischemia for 60 min; and group 3, which received a sequence repeated four times of 15 min ischemia and 10 min reperfusion. The portal endothelin-1 level became significantly elevated after reperfusion compared to that before ischemia in all groups, being significantly higher in group 2 than in the other groups. The systemic endothelin-1 level also increased after reperfusion; significantly in group 2. The portal endothelin-1 level was generally higher than the systemic level, which again was statistically significant in group 2. After 2 h of reperfusion, a significant positive correlation was found between the portal endothelin-I level and serum LDH, whereas a significant negative correlation was found between the portal endothelin-1 level and TBF. The finding that the portal endothelin-1 level became elevated after hepatic ischemia/reperfusion suggests that it probably plays an essential role in hepatic ischemia/ reperfusion injury by adversely influencing tissue microcirculation.

Continuous measurement of tissue oxygen and carbon dioxide gas tensions in dog liver in ischemia/reperfusion.

An experiment was conducted to determine whether the oxygen and carbon dioxide gas tensions in liver tissue (PtO2 and PtCO2, respectively) reflect the state of microcirculation and/or metabolism in the ischemic liver. Subjects were divided into three groups: group 1, 30 min ischemia; group 2, 60 min ischemia; group 3, four times of intermittent 15 min ischemia after every 10 min of reperfusion. PtO2, PtCO2 and tissue blood flow (TBF) were measured by mass spectrometry, comparatively studied with the serum GOT level as an indicator of liver tissue damage. Furthermore, the time point at which the PtCO2 increase for 1 min initially became less than 1/2 of the maximum value was located on the transit curve of PtCO2, referred to as the critically anaerobic (CA) point, with which new indices of critically anaerobic score (CAS) and time (CAT) (see details in text) were developed. The profiles of PtO2 and PtCO2 during ischemia and reperfusion were clearly demonstrated, and the CA point was observed 12.7 +/- 2.9 min after induction of ischemia. PtO2 was positively correlated with TBF and negatively with the serum GOT level. Furthermore, not only CAS but also CAT were significantly correlated with PtO2, TBF, and the serum GOT level. It was concluded that PtCO2 reflects the state of anaerobic tissue metabolism during ischemia and PtO2 reflects the magnitude of microcirculatory disturbance and tissue injury caused by ischemia/reperfusion. Therefore, continuous monitoring of not only PtO2 but also PtCO2 is beneficial for patients undergoing hepatic surgery with ischemia.

Coronary fistulous communications with left ventricular chamber and giant mural thrombus after myocardial infarction.

Selective coronary arteriography, performed in a 67-year-old man with post-infarction angina, demonstrated severe three vessel disease and coronary fistulous communications with the left ventricular chamber adjacent to a giant mural thrombus formed in the apical aneurysm. Most of the contrast media seemed to empty directly into the chamber without presenting hypervascular blushes of the thrombus itself. This was somewhat different from the observation previously reported in a case with coronary fistulae associated with a post infarction mural thrombus. It was stressed that one should not misinterpret this condition as a rare coronary artery-cardiac chamber shunt associating myocardial infarction.