FK 506 inhibits tolerance induction in mice liver transplantation.

BACKGROUND: In the orthotopic mouse liver transplantation model, allografts are accepted without immunosuppression, and donor-specific tolerance is induced upto 40 days. Although FK 506 is a well-known immunosuppressive agent, its influence on tolerance induction is not known. In this study, we examined the influence of FK 506 on tolerance induction in a mouse liver transplant model. METHODS: Orthotopic liver transplantation was performed from B10.BR (H-2K) to B10.D2 (H-2D mice). In the experimental group, FK 506 (1 mg/kg/d) was given subcutaneously to the recipients from day 0 to day 21, whereas the control group received a placebo (1 mg/kg/d). On day 40, donor skin grafts were transplanted to the recipients to examine the survival times of the recipients and the skin grafts. On day 14, donor-type cells in recipient's blood, spleen, kidney, thymus, and lymph nodes were examined by RT-PCR using specific donor-type MHC class I and II primers. RESULTS: All recipients survived for more than 100 days. The mean survival time of skin grafts in the experimental group was significantly reduced compared to that of controls. On day 14, either donor-type MHC class I- or class II-positive cells were detected in the control group, whereas donor-derived MHC class II-positive cells disappeared in the experimental group. CONCLUSIONS: In the early period after mouse liver transplantation, FK 506 inhibits tolerance induction paradoxically. Some donor-derived MHC class II-positive cells might play an important role in tolerance induction.

Desmoplastic response in scirrhous gastric carcinoma: imbalance between collagen synthesis and degradation.

BACKGROUND: Scirrhous gastric carcinoma is characterized by a marked deposition of collagen in the stroma and has a very poor prognosis. MATERIALS AND METHODS: To elucidate the fibrotic mechanism in scirrhous gastric carcinoma, we measured the activities of the collagen synthetic enzyme, prolyl 4-hydroxylase (P4H) and the collagen degrading enzymes, interstitial collagenase and type IV collagenase, in tissue from patients with advanced gastric carcinoma. Concentrations of P4H and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the sera of patients with gastric carcinoma were measured using sandwich enzyme immunoassay systems. We performed immunohistochemical analysis for TIMP-1. RESULTS: Enzyme activities of P4H, interstitial collagenase and type IV collagenase in the tumor samples of scirrhous gastric carcinoma were significantly lower than those of non-scirrhous gastric carcinoma (p < 0.01). Serum concentration of TIMP-1 in patients with diffuse type carcinoma was significantly higher than in patients with intestinal type carcinoma and control subjects (p < 0.05). We demonstrated stromal expression of TIMP-1 in scirrhous gastric carcinoma tissue. CONCLUSION: These data suggest that decreased collagenase activity and increased expression of TIMP-1 would result in collagen deposition in scirrhous gastric carcinoma tissue.

Hemodynamic analysis of findings in patients with portal hypertension: multicenter analysis in Japan. Japan Portal Hypertension Study Group.

BACKGROUND/AIMS: A multicenter study was done to assess the pathophysiology of malcirculation with portal hypertension. PATIENTS AND METHODS: Patients were admitted to 48 different institutes from 1990 to 1992. RESULTS: Portal venous pressure was 345.9 +/- 72.1 mmH2O in patients with portal hypertension. In patients with liver cirrhosis, the diameter of the splenic artery, of the proper hepatic artery, of the left gastric artery and of the splenic vein was significantly larger (p<0.05) than seen in the controls without portal hypertension. In patients with idiopathic portal hypertension, the diameter of the splenic artery and of the vein was significantly larger (p<0.05) and that of the proper hepatic artery was significantly smaller (p<0.05) than seen in the cirrhotic patients. In the cirrhotic patients, blood flow volume was significantly larger (p<0.05) in the splenic vein. In patient with idiopathic portal hypertension, blood flow volume in the portal vein and splenic vein were significantly larger (p<0.05) and that of superior mesenteric vein showed an increasing tendency to enlarge. CONCLUSION: This study shows that a hyperdynamic state is present in patient with portal hypertension.

Evaluation of asialoglycoprotein receptor imaging agent as a marker of hepatic ischemia-reperfusion injury and recovery.

Protection of hepatocytes from ischemia-reperfusion injury is a clinically important issue. The purpose of this study was to evaluate changes in acute liver damage and recovery after ischemia-reperfusion in rats with asialoglycoprotein receptor (ASGP-R) ligand. Ischemia was induced by clamping the hepatoduodenal ligament for 90 min. At 1, 3, 24, 48 hr, 1 and 2 wk after reperfusion, I-125-GSA was injected. Five min after injection, blood samples were obtained and the liver was removed. Several regions from each lobe were dissected, weighed and counted. Mean uptakes (% dose/g) in the liver and blood samples were calculated. Histologic sections stained with hematoxylin-eosin (H-E) stain showed ischemic damage at 1 and 3 hr, and focal hepatocyte necrosis at 24 hr. Predominant massive necrosis was not seen. The mitotic index with H-E stain and proliferating cell nuclear antigen (PCNA) labeling index were highest at 1 wk, indicating liver regeneration. At 1 and 3 hr, liver uptake was significantly decreased, and blood uptake was significantly increased, indicating decreased tissue blood flow and ischemic damage. Liver uptake showed significant increases at 48 hr and 1 wk, and was the highest at 1 wk, indicating liver regeneration during the convalescence stage. ASGP-R binding may provide valuable information on ischemia-reperfusion injury and recovery.

Gastrointestinal stromal tumor of the stomach successfully treated by laparoscopic proximal gastrectomy with jejunal interposition.

The authors describe a patient with a bleeding gastrointestinal stromal tumor of the stomach who was treated successfully by laparoscopic proximal gastrectomy with jejunal interposition. Immunohistochemically, the tumor was positive for vimentin and CD34 and was diagnosed as a gastrointestinal stromal tumor of low-grade malignancy. Because it is difficult to diagnose this disease preoperatively and a malignant phenotype has been reported, resulting in liver metastasis and peritoneal dissemination, it is desirable to treat this disease with as little manipulation as possible. To achieve this, laparoscopic surgery is a feasible option for the treatment of gastrointestinal stromal tumors.

Purely laparoscopic pylorus-preserving gastrectomy with extraperigastric lymphadenectomy for early gastric cancer: a case and technical report.

For the purpose of prevention of postgastrectomy syndrome and a less invasive and yet curative oncological resection, a purely laparoscopic pylorus-preserving gastrectomy with extraperigastric lymphadenectomy was performed for a patient with early gastric cancer located in the middle third of the stomach. The patient's postoperative course was uneventful. During his postoperative recovery, the patient experienced very little pain and used analgesic medication only one time. This operation appeared to be oncologically adequate. As of the seventh postoperative month, the patient never experienced dumping syndrome or alkaline reflux gastritis. This procedure is technically feasible and an excellent option because of its reduced surgical invasiveness and better postoperative quality of life.

[Etiology and hemodynamics of esophago-gastric varices].

The hemodynamics of the portal area, particularly of the left gastric vein in cases of esophago-gastric varices with portal hypertension have revealed that only one-third are featuring hepatofugal collateral flow (Type I), while hepatopetal and/or to and fro flow (Type II) forms make up about two-thirds. Furthermore, regarding the supply of blood to the varices, in all cases a contribution of arterial blood inflowing through the left gastric artery to the upper part of the stomach was found. Therefore, concerning the etiology of varices other than that due to hepatofugal collaterales, a hyperdynamic state of the upper part of the stomach area has been considered as an important factor. With regard to the micro-circulation of the gastric wall, it was proved that the hyperdynamic state was caused by an increase in submucosal arterio-venous anastomoses, and this was concluded to be directly responsible for the etiology of the varices. Therefore, the appropriate therapeutic approach to varices should as the rule be based on interruption both of hepatofugal collaterales and arterial flow, or the drainage of the hypertensive state of the local venous system.

Laparoscopic pancreas-preserving total gastrectomy for proximal gastric cancer. A case and technical report.

Although total gastrectomy with distal pancreatectomy has been the standard surgical treatment for advanced gastric cancer, this procedure is frequently complicated by leakage of pancreatic juice and postoperative diabetes mellitus. We present the case of a 74-year-old woman with proximal gastric cancer who underwent a laparoscopic modification of an open pancreas-preserving procedure first described by Maruyama et al. in 1995. With this novel technique, there is no pancreatic leakage, and at 12-month follow-up our patient remains free of diabetes. Herein we give the details of our new method and offer some caveats for its performance.

Laparoscopic side-to-side esophagogastrostomy using a linear stapler after proximal gastrectomy.

In order to improve anastomotic procedures, we performed laparoscopic side-to-side esophagogastrostomy, using a linear stapler, after proximal gastrectomy in two patients with gastric cancer located in the upper third of the stomach. The patients' postoperative courses were excellent. During postoperative recovery, the patients experienced very little pain, used no analgesic medications, and never experienced reflux esophagitis. This procedure is technically feasible and is an excellent option, given the less involved anastomotic procedure and better postoperative quality of life compared with these features in end-to-side anastomosis using a circular stapler.

Alliinase [S-alk(en)yl-L-cysteine sulfoxide lyase] from Allium tuberosum (Chinese chive)--purification, localization, cDNA cloning and heterologous functional expression.

Alliinase [S-alk(en)yl-L-cysteine sulfoxide lyase], a pyridoxal-phosphate-(Pxy-P)-dependent enzyme, is responsible for the degradative conversion of S-alk(en)yl-L-cysteine sulfoxide to volatile odorous sulfur-containing metabolites in Allium plants. We have purified alliinase from shoots of Allium tuberosum (Chinese chive) to apparent homogeneity by SDS/polyacrylamide gel electrophoresis. A cDNA clone encoding alliinase was isolated from a cDNA library constructed from whole plants of A. tuberosum by hybridization screening with a synthetic 50-residue oligonucleotide encoding a conserved region of the alliinases from onion and garlic. The isolated cDNA encoded a protein of 476 amino acid residues with a molecular mass of 54083 Da. The deduced amino acid sequence exhibited 66-69% identities with those of reported alliinases from onion, garlic and shallot. The partial amino acid sequence, which was determined for a V8 protease-digested peptide fragment of the purified alliinase, was perfectly matched with the sequence deduced from the cDNA. An expression vector of recombinant alliinase cDNA was constructed in yeast. The catalytically active protein was in the soluble fraction of transformed yeast. Site-directed mutagenesis experiments indicated that Lys280 was essential for the catalytic activity and, thus, a possible Pxy-P-binding residue. The mRNA expression of the alliinase gene comprising a multigene family in the shoots of green plants was twofold higher than that in the roots of green plants; however, the expression in the shoots of etiolated plants was only 13% that in green shoots, although the expression in the roots was not remarkably different between in green and etiolated plants. Immunohistochemical investigation indicated that the alliinase protein is predominantly accumulated in the bundle sheath cells of shoots of A. tuberosum.

Laparoscopic right hemicolectomy with radical lymph node dissection using the no-touch isolation technique for advanced colon cancer.

The treatment of advanced right-sided colon cancer presents numerous challenges for the surgeon who must aim to minimize the invasiveness of surgery, achieve curative resection, and prevent port-site recurrences. To overcome these issues, we performed a totally intra-abdominal laparoscopic right hemicolectomy with radical lymph node dissection based on a no-touch isolation technique. To perform this no-touch technique, we initially dissected the lymph nodes along the surgical trunk, then transected the transverse colon, terminal ileum, and mesentery without tumor manipulation. Finally, the right side of the colon was freed retroperitoneally. We performed this surgical technique on three patients and no intraoperative complications were encountered. Curative resection was achieved in all three patients, as curability A according to the Japanese Classification of Colorectal Carcinoma, and their postoperative courses were uneventful. Therefore, this novel technique proved to be both feasible and safe. Furthermore, it enabled us to minimize the invasiveness of surgery, while providing clear access to resect the right-sided advanced colon cancer.

Precancerous conditions of biliary tract cancer in patients with pancreaticobiliary maljunction: reappraisal of nationwide survey in Japan.

It is widely known that pancreaticobiliary maljunction (PBM), an anomalous arrangement of the pancreaticobiliary ductal system, is frequently associated with biliary tract cancer in patients with or without bile duct dilatation. In 1985, we surveyed patients with PBM who had been operated on at 133 Japanese institutions. A close relationship was shown between biliary tract carcinogenesis and PBM, according to the type of maljunction and age distribution: PBM patients with cystic dilatation had a high risk of bile duct cancer, even in those who were young (aged less than 20 years); the incidence of gallbladder cancer increased markedly in PBM patients over 40 years old with cystic dilatation, while it gradually increased with age in the PBM patients without cystic dilatation. Therefore, we recommend surgical treatment for patients with PBM even if they have no symptoms.