We investigated the biological aggressiveness of endocrine cell carcinoma (ECC) (small cell carcinoma) of the stomach, which clinically had a poor prognosis, from the point of view of the cell proliferation activity using the PCNA Labeling Index and the MIB-1 Labeling Index. The PCNA Labeling Index of the ECCs (22 cases) was 56.3% on average, while the MIB-1 Labeling Index was 53.9% on average. These rates were significantly higher than either the PCNA Labeling Index (average 40.3%) or the MIB-1 Labeling Index (average 29.9%) of oridinary tubular adenocarcinomas examined as control cases (20 cases) (p<0.01). Moreover, in ECCs (6 cases) accompanied by ordinary tubular adenocarcinoma, the PCNA Labeling Index (average 53.8%) and MIB-1 Labeling Index (average 56.2%) in the ECC component were significantly higher than the PCNA Labeling Index (average 42.3%) and the MIB-1 Labeling Index (average 41.9%) in the ordinary tubular adenocarcinoma component in the same tumor (p<0.05). Consequently, we consider ECC to be more aggressive than ordinary tubular adenocarcinoma on the basis of its cell proliferation activity.

View full abstract

In order to evaluate the operative risk before hepatic resection, the histological activity index (HAI) score of non-cancerous liver tissue obtained by needle biopsy was calculated in 58 patients with hepatocellular carcinoma receiving hepatic resection. No correlation was found between the HAI score and aspartate aminotransferase, alanine aminotransferase or total bilirubin before surgery, while significant correlations were observed between HAI score and intraoperative blood loss (r= 0.53, p<0.01). The HAI scores of the patients with the postoperative complication were significantly higher than those without complication (p<0.05). Further, a stepwise logistic regression analysis showed that a category IV (fibrosis) of HAI was significantly associated with the occurrence of postoperative complications (odds ratio 2.74, p=0.011). Moreover, postoperative complications were experienced frequently in patients received lobectomy with the HAI score 6 or more and in patients received segmentectomy or less with that 10 or more. In conclusion, preoperative histological assessment of non-cancerous liver using the HAI score system is useful for risk prediction in patients receiving hepatic resection.

View full abstract

We studied surgical treatment for anomalous arrangement of the pancreaticobiliary ductal system without dilatation of the common bile duct in 18 of 38 patients. The remaining 20 patients were excluded from the study because of the complication of carcinoma (carcinoma of the gallbladder in all 20 patients). Extrahepatic bile duct excision and reconstruction of the bile duct was performed on 4 patients with pancreatitis or cholangitis due to the pancreaticobiliary anastomotic anomaly and cholecystectomy alone was performed on the remaining 14 patients. The resected gallbladders showed mucosal hyperplasia or metaplasia, while no such changes were seen in the bile duct mucosa in the 4 patients who received extrahepatic bile duct excision. The postoperative course of the 14 patients receiving cholecystectomy alone was followed with blood chemistry studies and imaging studies over an average period of 4 years and 5 months (with a range of 13 months to 9 years and 8 months). The postoperative course of all 14 patients was uneventful, and none of them had abnormalities due to remnant pancreaticobiliary anastomotic anomaly. Further prolonged follow-up is warranted in our series of patients, but these results suggest that cholecystectomy can be advocated in anomalous arrangement of the pancreaticobiliary ductal system without dilatation of the common bile duct, if pancreatitis or cholangitis due to the pancreaticobiliary anastomotic anomaly can be precluded.

View full abstract

The effect of autonomic denervation and/or truncal vagotomy on visceral blood flow was studied with 15 dogs. The tissue blood flow in the duodenum, jejunum, and pancreas was measured by the hydrogen gas clearanace method. Blood flow of the portal vein was measured with an ultrasonic transit-time blood flow meter. The vasoactive intestinal polypeptide (VIP) concentration in the portal vein was also measured by the radioimmunoassay double antibody method. In the group receiving dissection of the celiac and cranial mesenteric plexus, postoperative diarrhea occurred. The blood flow in the duodenum, jejunum and portal vein decreased, while the pancreatic blood flow and portal VIP concentration increased after surgery. In the group receiving truncal vagotomy, diarrhea did not occur after truncal vagotomy. There was no significant blood flow change in the doudenum and jejunum after truncal vagotomy, whereas the blood flow in the pancreas and portal vein decreased. The portal VIP concentration increased slightly after surgery. These findings suggest that the upper abdominal autonomic denervation produced the diarrhea and significant change in visceral blood flow.

View full abstract

A 40-year-old man, who had undergone surgery for an anal fistula in June 1992, was hospitalized three times for paraumbilica I pain. In June 1993, he was readmitted with fever and an infra-umbilical tumor. Barium meal examination revealed segmental stenoses and a cobblestone appearance in the ileum and ileal Crohn's disease was diagnosed. And abdominal computed tomography showed a massive heterogeneous lesion on the ventral side of the inferior vena cava, suggesting an intraabdominal abscess due to perforation of the ileal lesions. Surgical findings revealed a retroperitoneal abscess at the root of the mesentery connected to an ulcerative lesion in the third portion of the duodenum. Under a diagnosis of duodenal involvement of small intestinal Crohn's disease, partial duodenectomy and duodenojejunostomy were performed with ileocecal resection and ileocolostomy for the ileal stenotic lesions. To the best of our knowledge, this is the first report of duodenal Crohn's disease with a penterating lesion located in the third portion causing a retroperitoneal abscess. Because duodenal involvement of Crohn's disease is very rare in Japan, our knowledge of its clinical features is still deficient and thirty cases of duodenal involvement of Crohn's disease in the Japanese literature were discussed.

View full abstract

We performed microwave coagulonecrotic therapy (MCT) by transthoratic approach in two cases of recurrent hepatocellular carcinoma after hepatectomy, and obtained good postoperative results. Case 1 was a 74-year-old man who had undergone hepatic resection twice. Massive bleeding was encountered during adhesiotomy in the second operation, and he was found to have recurrence again in S7. Case 2, a 62-year-old man, showed tumor recurrence in S8 of the liver after the partial resection of S4. In both cases the recurrent tumor was solitary and located near the surface of the liver under the diaphragma. Liver function did not permit conventional hepatic resection. Therefore, MCT by a transthoracic approach was chosen for the treatment of these tumors. In case 1, MCT was performed transdiaphragmatically, and in case 2, a coagulation needle was inserted after opening the diaphragma. In each case the blood loss was minimal and the postoperative course was satisfactory. The effective destruction of the tumor was ascertained by postoperative CT examination. This approach was considered to be an effective and less invasive surgical intervention for cases of recurrent hepatocellular carcinoma after hepatic resection.

View full abstract

Adenosquamous carcinoma of the liver is the rare disease, and few resected cases have been reported in the world wide literature. We experienced three resected cases of adenosquamous carcinoma of the liver, and in this paper, we discussed the clinical and pathological features. The case 1 was a 57-year-old woman. We performed left lobectomy and the size of resected tumor was 15×13.5×9 cm. She died in recurrence 4 months later. The case 2 was 74-year-old woman. We performed left and caudal lobectomy. The size of resected tumor was 7×7×5 cm. She died in reccurence 11 weeks later. The case 3 was 68-year-old man. We performed extended right lobectomy and caudal lobectomy, and co-resected a part of the common bile duct and portal vein. The resected tumor was 4×3 cm in size, and he died in bone metastasis 3 months later. Adenosquamous carcinoma of the liver has tends to grow more rapidly and to develop lymph node metastasis frequently. Thus its prognosis is very poor and it is difficult to treat this disease. Further studies would be mandatory for its improveemnt of prognosis.

View full abstract

Bile duct carcinoma is difficult to diagnose in the early stage. We present a case of non-icteric early bile duct carcinoma in the mucosal layer, 35×50mm in size. The patient, an 82-year-old woman, was admitted to our hospital. She complained of nausea and had liver dysfunction (elevation of LAP and γ-GTP) with out jaundice. The findings of abdominal ultrasonography (US) of this patient were dilatation of the extra-hepatic bile duct and a mass lesion in the middle bile duct. Percutaneous transhepatic cholangiography (PTC) showed a 45mm filling defect in the middle bile duct, indicating incomplete obstruction. Laparotomy was performed. Among the peritoneal findings, we could not detect ascites or lymph node swelling. Resection of the gallbladder and extra-hepatic bile duct, and hepaticojejunostomy (Roux-en-Y) were done. The size of the tumor was 35×50mm. Pathological analysis after surgery revealed papillary tumor of the bile duct, which was characterized as papillary adenocarcinoma, well differentiated, located in the mucosal layer (Bm-Bs-C, m, hinf₀, ginf₀, n1 (-), Stage I). She has been well for 13 months after surgery and is without recurrence.

View full abstract

We report a case of pancreas head carcinoma associated with stenosis of the celiac axis (SCA). Pancreatoduodenectomy was safely performed while evaluating hepatic arterial flow by electromagnetic flowmetry.The patient is a 52-year-old man, and his angiogram showed the arcade of the pancreas head was remarkably dilated, and the hepatic and splenic arteries were imagedt hrough the inferior pancreatoduodenal and gastroduodenal arteries.The lateral view of the aortogram revealed compression in the celiac axis.He was diagnosed as having pancreas head carcinoma with SCA.the intraoperative left hepatic arterial flow was 20ml/sec ordinary, 20ml/sec under clamping of the gastroduodenal artery, and 26 ml/sec after cutting of the gastroduodenal artery and the median arcuate ligament.During surgery for pancreas head tumors with SCA, it is essential for preventing postoperative complications to measure the hepatic arterial flow.

View full abstract

A 69-year-old man with the chief complaint of epigastralgia was admitted to our hopsital. Endoscopic retrograde cholangiopancreatography revealed pancreas divisum. The dorsal pancreatogram via the minor papilla showed an irregular stenosis, 2.5cm in length, in the pancreas head, and an obstruction distal to the stenosis. The ventral pancreatogram showed no malignant changes, Computed tomography revealed a mass, 4cm in diameter, in the pancreas head with invasion to the portal vein. Preoperative diagnosis was dorsal pancreatic cancer with pancreas divisum. A pancreatoduodenectomy with combined resection of the portal vein was performed. Macroscopic examination of the resected specimen disclosed a nodular mass, 3.5×3.8×4.0cm in size, which occupied the most area of the pancreas head with normal ventral pancreas at the inferior margin. Only 25 cases of pancreas cancer with pancreatic divisum have been reported in the Japananese literature including our case. The pancreatic carcinomas developed in the dorsal pancreas in 24 of 25 cases, and obstructive jaundice occurred in two of 25 cases.

View full abstract

Four cases of diverticulum or diverticulitis of the appendix were reviewed. All patients were males. The ages of the patients ranged from 35 to 64 years. In all cases, appendectomy was performed under suspicion of acute appendicitis. Pathologic examinations were conducted. In case 1, a diverticulum of the appendix was markedly inflamed. In case 2, inflammation was seen not only in the appendix but also in an acquired diverticulum. In case 3, acute appendicitis and an aquired diverticulum that was not inflamed were recognized. In case 4, only an acquired diverticulum of the appendix was inflamed. A diverticulum or diverticulitis was recognized or diagnosed after histological examination of the whole appendix. Therefore it is very important to examine the whole appendix histologically in order to avoid overlooking diverticula and diverticulitis of the appendix.

View full abstract

Complications after pancreato jejunostomy were investigated according to the type of anastomosis, and the usefulness of continuous intraabdominal suction drainage (CISD) was evaluated. One hundred and forty three patients were included in this study. The invagination method (type I) was used in 20 patients, the duct-insertion method with seromyotomy (type II) in 22, the duct-insertion method without seromyotomy (type III) in 48, and pancreaticojujunostomy followed by total layer anastomosis (type IV) in 53. The incidence of pancreatic fistula was 20% in the type I group, 21% in type II, 0% in type III, and 13% in type IV. The incidence of anastomotic leakage was 25%, 14%, 6%, and 4%, respectively. There was a significant difference in the frequency of anastomotic leakage between pancreatic cancer and biliary tract cancer (5% in pancreatic cancer versus 14% biliary cancer). Postoperative early death occurred in 25% of the patients in the type I group, 14% in type II, 12% in type III, 6% in type IV. There was a tendency toward a correlation between postoperative early death and anastomotic complications in the non-CISD group (p=0.06). However, there was no correlation between the two factors in CISD group. These results indicate that pancreaticojunostomy followed by total layer anastomosis and CISD are useful and safe procedures after pancreaticoduodenectomy.

View full abstract

Previous studies found that overexpression of the epidermal growth factor receptor (EGF-R) and reduced expression of E-cadherin and α-caenin were associated with lymph node metastasis of esophageal cancer. In the present study, we examined whether EGF was in part responsible for the dysfunction of cadherin-mediated cell-cell adhesion in the human esophageal cancer cell line TE-2R, which expresses E-cadherin and EGF-R. In the presence of EGF, TE-2R changed its colony formation from compact to sparse. In the cell dissociation assay, EGF strongly facilitated the dissociation of TE-2R cells in a dose-dependent manner. Moreover, EGF enabled the cells to invade an organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its location from the lateral adhesion site to the whole cell surface. Finally, we observed tyrosine phosphorylation of β-catenin induced by EGF. These results suggest that EGF might counteract Ecadherin mediated cell-cell adhesion through phosphorylation of β-catenin and modulate tumor cells to a more aggressive phenotype for lymph node metastasis of esophageal cancer.

View full abstract

To defermine the influence of surgical stress on metastasis, we counted the metastatic colonies on the surface of the lung after inoculating melanoma cells into the tail veins of mice that underwent surgery. The surgical stress increased the number of metastatic colonies. To prevent host immune suppression after surgery, BRM (OK432) was administered to the mice preoperatively. Preoperative oral administration of OK432 inhibited the enhancement of metastasis by surgical stress in the murine experiment. Clinical investigation demonstrated that Stage III and IV gastric cancer patients showed a decrease in Con A-induced lymphocyte blastogenesis, and Stage IV patients also showed a decrease in NK activity after surgery. But preoperative oral administration of OK432 inhibited these decreases. NK cells are considered to play an important role in prevention of distanat metastasis, and the enhancement of metastasis may be due to the suppression of NK activity after surgery. The study suggests that preoperative administration of BRM could inhibit the enhancement of metastasis gy maintaining the NK activity after surgery.

View full abstract

In this study, using pancreatic cancer cell lines, we investigated the role of carbohydrate expression, ELAM-1 binding and cytokines in liver metastasis of pancreatic cancer, and the possible therapeutic application of a glycosylation inhibitor. SW1990 cells revealed a high metastatic potential (90%) in the intrasplenic injection model, and this metastatic ability was correlated with its high carbohydrate expression (sialy-Le^a & Le^x) and high adhessiveness to HUVECs and ELAM-1. By coculture of SW1990 cells with peripheral mononuclear leukocytes, high production of TNF-αand IL-1β occurred in the medium, and this medium could induce expression of ELAM-1 on HUVECs. A glycosylation inhibitor (BZN) inhibited carbohydrate expression, ELAM-1 binding and liver metastasis of SW1990. These findings suggest a possible new therapeutic application of BZN for metastasis.

View full abstract

Sialyl Lewis-X antigen (sLe^x) and sialy Lewis-a antigen (sLe^a) are expressed in colorectal carcinomas and were recently shown to be a Iigand for endothelial adhesion molecule E-selectin. In order to determined whether expression of cell surface sLex and sLe^a is associated with the metastatic potential of human colorectal carcinoma (CRC), we examined sLe^x and sLe^a expression in tissue samples obtained from 159 CRC patients to investigate whether this antigen expression could serve as a prognostic parameter, and examined metastatic phenotypes in variant CRC cell lines for high and low cell surface levels of sLe^x (KM12HX and KM12LX, respectively). Clinical records showed that the disease-free survival rate for CRC patients with high levels of sLex was significantly poorer than for patients with low levels of this antigen. Cox's multivariate analysis revealed that the sLex expression level was one of the significant discriminants of recurrence in colorectal cancer patients. KM12HX showed a higher metastatic potential in nude mice and greater adhesive ability in vitro than KM12LX cells. This increased adhesiveness of KM12HX was inhibited by anti-E-selectin antibody, an inhibitor of carbohydrate synthesis, benzyl-N-acetyl-α-D-galactosaminide, and sialidase. These results suggest that sLe^x expression could be involved in colon cancer metastasis and that sLe^x might prove to be a potent marker of recurrence in CRC patients. Also, they suggest the possibility of regulation of the metastatic potential of CRC by inhibition of carbohydrate antigen synthesis.

View full abstract

Messenger RNA expression of matrix metalloproteinase (MMP) 2, 7, 9 was examined in surgical specimens of colorectal cancers. OnIy MMP-7, matrilysin, mRNA was limitedly expressed in cancer, but not in surrounding tissue. Its expression was associated with progression of colorectal tumors with the maximum in liver metastatic tumors. Antisense oligonucleotides for matrilysin suppressed matrilysin mRNA expression in a matrilysin-producing rectal cancer cell line, CaR-1, resulting in inhibition of cell proliferation and the invasiveness of this cell line dose dependently. We conclude that matrilysin is a promising candidate as a new clinical diagnostic and prognostic marker of colorectal cancers as well as antisense oligonucleotide therapy.

View full abstract

In order to determine the role of cell adhesion molecules in the process of cancer invasion and metastasis, we administered the cell-binding domain to a mouse liver metastasis model, and assessed the prevention of cancer metastasis resulting from inhibition of adhesive interaction with cancer cells. A liver metastasis model was created by injecting 1×10³ colon 26/TC11 cells into the anterior mesenteric vein of CDFI mice. The cell-binding domain was obtained by extracting and purifying fibronectin from human plasma, and partially purifying only the domain which includes RGD. A fibronectin-treated group, a fibronectin binding domain-treated group, and a control group were established, The animals were sacrificed four eeks later, and the metastatic liver nodules were courlted. The results showed that metastasis was more advanced in the fibronectin group than in the control group, and about 50% inhibition was observed in the fibronectln binding domain-treated group (10μ of fibronection per ml). These findings suggest that, as a metastasis-inhibiting substance, the binding domain may become an effective means of anti-adhesion therapy by competing with native adhesiorl molecules on the cancer cell surface uring the metastatic rocess, and blocking adhesion.

View full abstract

The potential for hepatic metastasis in nude mice was studied by the intrasplenic implatation method with three human pancreatic cancer cell lines, Capan-1, BxPC-3, and MIAPaCa-2, especially in relation to serine protease expression. The inhibitory effect of a protease inhibitor agent, FOY-305, on hepatic metastasis was also assessed. In addition, we examined these cell lines, for expression of he vacuolar type proton pump (V-type ATPase), and determined the effect of its inhibitor agent, bafilomycin Al, on the cancer cell invasion in vitro by chemoinvasion assay using a MATRIGEL invasion chamber. The potential for hepatic matastasis was well correlated with expression of trypsinogen I (cationic isoform) in these cell lines, and the incidence of metastasis was significantly decreased by FOY-305. In addition, the potential for invasion in vitro in these cell lines was also significantly suppressed by bafilomycin Al. These findings suggest that pharmacologic inhibition of the activity of serine protease and V-type ATPase may be a new strategy for the therapy of pancreatic cancer invasion and metastasis.

View full abstract

For examining the pathway of hepatic metastasis of gastointestinal cancer, we established rat models of simple mesenteric lymphagiectomy and mesenteric lymph vessel obstruction. With these models, we carried out mesenteric lymphangiography and examined them for morphological changes in lymph vessels and lymph flow. In the model of simple mesenteric lymphagiectomy, the contrast material filled the intestinal lymph trunks and the thoracic duct in 3 of 5 animals on the 4th postoperative day and in all 5 animals on the 6th postoperative day, indicating lymph vessel recanalization. In the model of lymph vessel obstruction, we carried out mesenteric lymphangiography on the 6th postoperative day and obtained images of the mesenteric vein, the portal vein and the liver in all 5 animals. These images revealed lyphatico-venous communication induced by the mesenteric lymph vessel obstruction. In clinical cases of multiple hepatic metastasis of colonic cancer, carbonic particles injected into the paracolic lymph node were immediately detected in the portal blood. The lymphatico-venous communication is considered to be induced by lymph vessel obstruction, lymph retention and elevation of endolymphatic pressure. The presence of lymphatico-venous communication could be an important factor in the mechanism of hepatic metastasis of gastrointestinal cancer. This communication suggests the possibility of hematogenous metastasis via the lymphatic system.

View full abstract

The purpose of this study was to evaluate the problems and to estimate the possibility of living related liver transplantation (LRLT) from the viewpoints of complications and prognosis. One adult and 11 pediatric patients, including 8 with biliary atresia, 2 with Alagille syndrome, one with fulminant hepatitis and the one with primary sclerosing cholangitis, have received LRLT in Nagoya City University hospital. Three pediatric patients and the one adult were ABO-incompatible, one was ABO-compatible, and the remaining 8 were identical. Operations included 11 elective and one relative emergency operation, and were performed at intervals of 3 to 6 months. Five patients died within one month, whereas 7 cases could be followed alive for periods of 9 months to 4 years. The successfully treated patients were free from any liver damage due to administration of a single immunosuppressive drug: 4 treated with cyclosporine and 3 treated with FK506. The fatalities were due to massive infections related to hepatic decompensation from portal or hepatic arterial thromboses. The results of our LRLT were considered to depend upon the preoperative condition of the patients. Two of the 7 survivors were maintained on low doses of drugs. Two successful ABO-incompatible cases that were ABO group O, had markedly decreased anti-donor antibody titers, whereas they showed no marked changes in non anti-donor titers. We conclude that LRLT should be attempted as early as possible and before development of pronounced hepatic decompensation in those cases where it is indicated.

View full abstract

We report our experience with patient registration and care, and describe requirements for establishing a cadaveric liver transplantation protram in Japan. Since June 1991, 26 candidates have been evaluated for liver transplants (LTx) in our program. Of these, five patients had one or two concomitant hepatocellular carcinomas (HCCs) 1-2.5 cm in diameter, for which four were treated by ethanol injection. Five patients died waiting, and three underwent LTx abroad, while another received an ABO incompatible LTx from a non-heart beating donor in our program and died of multi-organ failure. Another patient lost candidacy for resuming drinking, leaving three waiting. Donor referral remains rare in Japan, where we encourage early patient registration in anticipation of long waiting, and now exclude malignancies other than a solitary HCC less than 2 cm, complicating non-B and Child C cirrhosis. Other requirements for a cadaveric liver transplant program were detailed.

View full abstract

Organ xenotransplantation is an attractive method to compensate for the cadaveric donor shortage. However, hyperacute rejection is a great barrier to successful organ xenotransplantation. In this study, the authors examined the effect of in vitro gene engineering with regulator of complement activation (RCA) molecules such as DAF and HRF20, and the possibility of applying in vivo gene enginerring to the xenogeneic liver and kidney using an adenoviral vector. It was concluded that complement activation is inhibited by the gene engineering with RCA molecules against the xenogeneic cells, and that an adenoviral vector is a useful method for in vivo gene engineering to the xenogenic organs.

View full abstract

Pancreatic islets were microencapsulated in an agarose hydrogel as a semipermeable membrane to prevent their xenorejection. We evaluated this bioartificical pancreas in discordant xenografting with or without administration of 15-deoxyspergualin (DSG). A 5% agarose suspension containing purified canine islets was emulsified in paraffin oil and solidified by cooling in an ice-bath. Canine islets were xenotrasplanted intraperitoneally in to BALB/c mice and NOD mice rendered diabetic with streptozotocin (220mg/kg body weight ip) and cyclophosphamide (200 mg/kg body weight ip), respectively. Graft survivals in BALB/c mice (37±28 days) and NOD mice (31±21 days) with microencapsulation were significantly longer than those without microencapsulation used as controls. With the combination of DSG (2.5mg/ kg per day) and microencapsulation, the islet xenograft survival (76±24 days, 75±27 days) could be extended much longer and indefinite graft survival was observed in two of seven, respectively. Regardless of whether, were low doses of DSG adminisered or not, mouse anti-dog antibody titer levels of BALB/ c were elevated to more than 50% two and four weeks after xenotransplantion of microencapsulated islets; however, their plasma glucose levels remained normal. Antibody-mediated damage to microencapsulated islet could not be detected. Combined therapy by agarose-microencapsulation and administration of DSG might be a promising strategy for clinical application to prevent rejection in discordant islet xenotransplantation.

View full abstract

Relationships between preservation injury and mucosal recovery of the graft intestine were investigated histologically, immunohistochemically and by computer morphometry. Rat graft intestines (n=9) were preserved with cold lactated Ringer's solution for 0, 6 and 12 hours and then used for orthotopic small bowel transplantation with pulse labeling of bromodeoxyuridine (BrdU) in the reperfusion period. Samples of the graft intestine were collected 1, 24 and 48 hours after transplantation and examined histologically and immunohistologically with anti-BrdU antibody. Histological examination showed that the grades of tissue damage after reperfusion were related to the duration of the graft cold ischemia. Morphometric analysis of labeled cells with NIH image on Macintosh computer revealed that both the labeling index 1 hour after surgery and the migrating velocity of the labeled cells 24 and 48 hours after surgery were higher in the order of 6, 12 and 0 hour preservation. these results indicate that preservation injury to the graft intestine would stimulate the proliferating activity of crypt cells resulting in the immediate recovery from the mucosal barrier damage, while the excessive injury suppressed the regenerative reaction. We conclude that our new methods of computer morphometry and analysis should be applicable to transplantation pathology.

View full abstract

Extrinsic denervation is inevitable after a conventional intestinal transplantation procedure and leads to poor intestinal function. In this study, reinnervation by extrinsic sympathetic nerves was investigated in rats morphologically by a glyoxylic acid fluorescence histochemical method. Further, a new intestinal transplantation procedure, in which extrinsic sympathetic nerves are preserved and transplanted with the intestinal graft, was developed. Reinnervation began in the arterial anastomosis 3 weeks after transplantation and extended from proximal to distal following the course of the mesenteric arteries. Reinnervation by fairly dense sympathetic nerve fibers, about 70 to 80% of the control, was found up to distal portion of the mesenteric arteries 1 year after transplantation. However, in the intestinal wall itself, although reinnervation began 15 weeks after transplantation, the density of reinnervating fibers was rather low even 1 year after transplantation. These results indicate that innervation of the intestinal wall, which plays an important role in graft function, remained poor, while sufficient reinnervation of the mesenteric arteries took place. In contrast, in our new experimental method, in which sympathetic postganglionic nerves remain attached to the intestinal graft, about 75 to 90% of control sympathetic nerve fibers were preserved and transplanted in the mesenteric arteries 3 weeks after transplantation and innervation of arteries in the intestinal wall was almost identical to the control level from 1 week after transplantation. Recovery of the sympathetic function may be achieved early on, if the grafted sympathetic nerves become appropriately connected to the recipient's nervoussystem.

View full abstract