Hiroshige Nakano

The serum interleukin 8 level reflects hepatic mitochondrial redox state in hyperthermochemohypoxic isolated liver perfusion with use of a venovenous bypass

BACKGROUNDnWe have recently developed a simple method of hyperthermochemohypoxic isolated liver perfusion (HILP) as a regional therapy for unrecognized liver micrometastases. However, little is known about the influence of HILP on cytokine production and liver function. We investigated the influence of HILP on interleukin 8 (IL-8) production and the hepatic mitochondrial function and assessed the relationship between these 2 parameters. We also measured the serum tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) levels to examine the involvement of HILP-induced cytokines in the tumor response.nnnMETHODSnSixteen patients with metastatic liver tumors were randomly assigned to undergo hepatectomy with HILP (group A, n = 9) or hepatectomy alone (group B, n = 7). The isolated liver was perfused for 30 minutes with Ringers lactate solution containing chemotherapeutic agents warmed to 42 degrees C to 43 degrees C without oxygenation.nnnRESULTSnThe serum IL-8 levels in group A were markedly increased, with peaks at 3 hours after reperfusion, which was significantly higher than levels in group B (P < .01). In group A the arterial ketone body ratio, which reflects the hepatic mitochondrial redox state, decreased during perfusion and was gradually restored to the preperfusion level 1 hour after reperfusion. However, in group B it decreased during hepatectomy but rapidly recovered 5 minutes after hepatectomy. There was a significant negative correlation between the peak serum IL-8 level and the initial velocity of arterial ketone body ratio recovery for the first 5 minutes after reperfusion r = -0.83, P < .001). The serum TNF-alpha and IL-1 beta were temporarily detected only in 3 of 9 patients in group A.nnnCONCLUSIONSnWe have shown that HILP resulted in augmented IL-8 release but not TNF-alpha and IL-1 beta and that the serum IL-8 level reflects the hepatic mitochondrial redox state. These findings suggest that IL-8 production may be associated with hepatic mitochondrial impairment during ischemia. This work may contribute to new therapeutic strategies not only for hepatic ischemia reperfusion injury but also for metastatic liver tumors.

Evaluation of initial hepatic allograft function with changes of free plasma amino acids in canine orthotopic liver transplantation

We investigated the correlation between amino acid level and hepatic graft function. Plasma amino acid levels were measured at three time periods during canine orthotopic liver transplantation. During the anhepatic phase, plasma amino acid levels rose except for tryptophan. Cystine and alanine (Ala) increased significantly to 210 +/- 28% (n = 20, mean +/- SEM) and 203 +/- 11% from preoperative values (100%), respectively. In animals successfully surviving without hepatic insufficiency after transplantation of fresh livers (n = 7), plasma amino acid levels were restored to preoperative values within 3 hr following reperfusion. On the other hand, in animals that died from hepatic insufficiency within 5 days after grafting of warm ischemically damaged livers (n = 8), plasma amino acids, especially Ala, phenylalanine, total free plasma amino acids, and aromatic amino acids progressively increased to 216 +/- 25, 274 +/- 36, 152 +/- 15, and 152 +/- 15% at 3 hr after reperfusion. These were significantly higher compared to those of the group of animals transplanted with fresh livers (P less than 0.01-0.05). Furthermore, higher values were found in those dogs transplanted with warm ischemically damaged livers surviving for shorter periods. Also in dogs that died from hepatic insufficiency within 8 hr after grafting of livers preserved for 24 hr (n = 5), amino acid levels were at high values at 3 hr. These results suggest that in animals having good graft function, plasma amino acid levels are restored to preoperative values by 3 hr after reperfusion. In other cases, primary nonfunction should be strongly suspected after liver transplantation.

Neurofibroma of the Stomach: Report of a Case

We report herein the case of a 71-year-old-Japanese woman who was admitted to hospital for surgical treatment of a lower abdominal tumor. At laparotomy the tumor was found to be pedunculated and growing extramurally from the greater curvature of the stomach. Thus, a wedge resection of the stomach, including the mass, was performed. The tumor measured about 9×8×7 cm and histological examination of the resected specimen showed that the main elements consisted of wavy, long-spindled cells, which crossed irregularly, indicating that it was palisading negative. Immunohistochemically, the specimen was positive for both S-100 protein and Alcian blue. From these findings, the tumor was histologically diagnosed as a neurofibroma. The patient had an uneventful postoperative course and no signs of recurrence have been recognized in the 3 years since her operation.

Intraductal carcinoma in a surgically resected pancreas with chronic pancreatitis

SummaryA 59-yr-old Japanese male presented with epigastralgia. Endoscopic retrograde cholangiopancreatography (ERCP) revealed narrowing of the inferior common bile duct and protein plugs in the main pancreatic duct. He was diagnosed as suffering from chronic pancreatitis with suspicion of a pancreatic head tumor, and a pancreatoduodenectomy was performed. Histologically, a diffuse chronic pancreatitis was evident in the resected pancreas. Although no tumors were seen in the head portion of the pancreas around the inferior common bile duct, an intraductal carcinoma was found in the second branch of Santorini’s duct. Precancerous alteration of the duct epithelium, presenting papillary hyperplasia, and atypical hyperplasia were observed in areas continuous with the intraductal carcinoma. Immunohistochemically, carcinoembronic antigen (CEA) was specifically expressed in atypical hyperplasia and intraductal carcinoma, but not in papillary hyperplasia.