T Ohyama

Serum Interleukin-6, Interleukin-8, Hepatocyte Growth Factor, and Nitric Oxide Changes during Thoracic Surgery

Abstract. Thoracic surgery creates a different environment from abdominal surgery in respect to the surgical procedure with pulmonary collapse under unilateral ventilation. Definitive evidence whether surgical trauma during thoracotomy is involved in postoperative pulmonary infections has not been clearly demonstrated. The objectives of this study were to evaluate the influence of surgical trauma during thoracotomy on postoperative infections and to investigate the clinical significance of postoperative humoral mediators in pulmonary infections after surgery. We measured serum interleukin-6 (IL-6), IL-8, hepatocyte growth factor (HGF), and nitric oxide (NO) levels in 27 patients undergoing thoracic surgery; the measurements were before and during thoracotomy, 60 minutes after reinflation, and after surgery. The patients were divided into three groups: lobectomy patients (group A), and esophagectomy patients without (group B) or with (group C) postoperative infections. The serum IL-6 and IL-8 levels in group C were markedly elevated 60 minutes after reinflation and were significantly higher than those in group A. The serum IL-8 levels during that period in group C were significantly higher than those in group B. The postoperative serum IL-6, IL-8, HGF, and NO levels were significantly higher in group C than in group B. Taken together, intraoperative hypercytokinemia, especially IL-8, following the thoracic procedure and subsequent reinflation preceded the clinical onset of postoperative infections. Hence postoperative serum IL-6, IL-8, and HGF levels may be useful predictors of infection after esophagectomy.

Repeat Hepatectomy for Recurrent Colorectal Metastases

Abstract. Recurrence rates after hepatic resection in patients with colorectal metastases are reported to range from 47% to 80%. Hepatic recurrence is seen in 35% to 50% of patients. Aggressive surgical resection appears to be a worthwhile treatment in patients with recurrent hepatic metastases to promote longer patient survival because surgical resection remains the only curative therapy available. This is a retrospective review of our experience with 15 patients undergoing repeat hepatic resection culled from 67 patients undergoing initial hepatectomy for metastatic colorectal cancer. Of 67 patients who underwent hepatectomy for colorectal hepatic metastases, 33 developed hepatic recurrence at a median interval of 23 months (range 1–176 months) after the first hepatectomy. The second hepatectomy was performed in 15 patients 5 to 29 months after the first hepatectomy, with no mortality. The mean operating time and blood loss at the second hepatectomy were similar to those at the first hepatectomy. The mean hospital stay at the second hepatectomy was significantly shorter than that at the first hepatectomy. The cumulative survival rate for the 15 patients was 42.4% at 3 years and 21.2% at 5 years, respectively, which compared favorably with the survival rate of the 67 patients who underwent initial hepatectomy. Patients who underwent the second hepatectomy had significantly higher survival rates from the first hepatectomy than the 18 patients with unresectable hepatic recurrence. Repeat hepatectomy can be performed safely and provides long-term survival rates similar to those of first hepatectomies. In appropriately selected patients, repeat hepatectomy for colorectal metastases is a worthwhile treatment.

Humoral Human Xenoreactivity Against Isolated Pig Pancreatic Islets

Abstract It is widely believed that the hyperacute rejection of vascularized xenografts in the pig-to-human combination is triggered by the binding of human preformed natural antibodies (PNAbs) to the Galα.(1,3)Gal epitope in pig endothelium and the subsequent activation of complement. However, it remains poorly defined whether xenogeneic pig pancreatic islets are damaged by antibody and complement-mediated mechanisms. We examined the expression of Galα(1,3)Gal on isolated adult pig islets and the presence of PNAbs in normal human sera directed against islets, using immunofluorescence staining and confocal laser scanning microscopy. The pig islets were not stained with Galα(1,3)Gal-specific lectin GSIB4; however, the exocrine cells reacted strongly with GSIB4, indicating that the Galα(1,3)Gal epitope was highly expressed on exocrine cells, but not on islets. Human sera showed weak reactivity of IgM and IgG class PNAbs to the islets, but strong reactivity to the exocrine cells. Furthermore, we investigated the cytotoxic effect of human serum on pig islets using an in vitro model of pig-to-human islet transplantation. The incubation of pig islets with normal human sera for 45 min resulted in less than 10% specific lysis despite the binding of PNAbs, whereas exposure of porcine aortic endothelial cells to the same human sera caused 56% complement-mediated lysis, determined using a MTT cytotoxic assay. These results support the view that pig islets might not undergo early antibody and complement-mediated rejection in humans.

Hyperthermo-Chemo-Hypoxic Isolated Liver Perfusion for Hepatic Metastases: A Possible Adjuvant Approach

As a possible intraoperative adjuvant approach to treating hepatic metastases we developed a method of hyperthermo-chemo-hypoxic isolated liver perfusion in combination with hepatic resection. This method was applied to 11 patients with colorectal hepatic metastases between 1992 and 1995. One patient died on postoperative day 14 of hepatic failure (9% mortality), the cause of which was live temperature that reached 42.9 degree C, which seems to be the maximum limit for thermal toxic effect on the human liver. The other 10 patients tolerated the perfusion well, with mild hepatic and non systemic toxicity after minor or even major hepatic resection; the serum aminotransferase and total bilirubin levels returned to normal levels by postoperative day 14. Only one of eight patients (13%) for whom cytotoxic drugs were added to the perfusate (mitomycin C 10 micrograms/ml or cisplatin 2 micrograms/ml) had hepatic recurrence by 19 months after the perfusion (mean follow-up 25.8 months; median 23 months; range 8-57 months). Two patients were alive with no evidence of disease at 13 and 57 months, respectively after the perfusion; the other five patients had postperfusion extrahepatic recurrences (median: 19 months; range 7-20 months). In contrast, hepatic metastases recurred 7 and 20 months after the perfusion, respectively, in the two patients not given a cytotoxic drug.

Comparison of hemodynamic changes in two veno-venous bypass techniques modified at the portal cannulation site

Veno-venous bypass under total vascular exclusion is a useful technique to permit safer resection of hepatic malignancy. We describe here a retrospective study of two modified venous bypass techniques as alternatives to the conventional end-on portal cannulation technique. Portal decompression via inferior mesenteric vein access was performed in eight patients (group A), and portal decompression via a passive shunt between a branch of the mesenteric vein and the right saphenous vein was performed in a second group (group B; n = 8). Both techniques were used in hepatic resection for malignancy under total vascular exclusion. To assess the efficacy of these bypass techniques, we compared the hemodynamic changes in the two groups. There were no differences in the bypass flow between the two groups. Neither group showed any significant changes in hemodynamic parameters (including mean arterial pressure, cardiac index, systemic vascular resistance index, and pulmonary artery pressure) between the pre-bypass and bypass phases. The heart rate in the bypass phase was significantly increased compared to that in the pre-bypass phase in both groups. All hemodynamic parameters in each phase were similar in the two groups. We conclude that both techniques maintained adequate venous return and stabilized the hemodynamic changes during hepatic resection under total vascular exclusion, and that either technique can be selected according to the intraoperative situation.

Predominant role of local immunosuppressive effect in enhanced efficacy of liposomal FK506 in organ transplantation

Liposomal FK506 is a new formulation of FK506 that increases FK506 levels in the liver and decreases them in the kidney in comparison to conventional IV formulation. In the present study, the efficacy of liposomal FK506 was evaluated in canine kidney and liver transplantation models. Liposomal FK506 increased the immunosuppressive efficacy of FK506 in the liver transplantation model, but decreased it in the kidney transplantation model. These results suggest that local immunosuppressive effects with increased intragraft FK506 level would play an important role in enhancing the immunosuppressive efficacy of liposomal FK506 in liver transplantation.