Duodenal ulceration into the cystic artery with massive hemorrhage.

This is a case presentation of a unique cause of intestinal bleeding. A duodenal ulcer eroded into the superficial branch of the cystic artery, causing massive intestinal hemorrhage. The patient, a 76-year-old woman, presented with left upper abdominal and left back pain secondary to cystic lesions in the pancreas body and tail. Stress after operation and complication of leakage of pancreatic juice after distal pancreatectomy with splenectomy and diclofenac sodium administration may have caused a deep peptic ulcer to erode the cystic artery. We performed a transfixing ligation of the bleeding vessel, serosal suture of ulcer of the gallbladder, and simple closure of the duodenal ulcer with covering greater omentum. There were no serious complications after the operation, and the patient made an uneventful recovery.

Factors that control extravascular fibrinolysis.

The physiological and pathophysiological state of tissues determines the exudation of plasma proteins, hemostasis, and fibrinolysis, i.e., inflammation, injury, and malignancy. The physiological controls of extravascular fibrinolysis ultimately rest on a balance between generation of the fibrinolytic enzyme(s), i.e., plasmin, elastase, cathepsins, etc., and inhibitors of the fibrinolytic enzyme(s), i.e., plasminogen activator inhibitors, alpha-2 plasmin inhibitor, alpha 1-protease inhibitors, etc. Moreover, it is the structural modification of fibrin that determines its stability toward proteolytic enzymes and physical duress. The structural modification of fibrin involves factor XIIIa-mediated cross-linking of interfibrin chains and alpha 2-plasmin inhibitor to fibrin. In turn, there are a number of agents that influence factor XIIIa catalytic activity (e.g., sulfhydryl agents, albumin, erythrocytes). The two key proenzymes, factor XIII and plasminogen, are tightly bound with the circulating fibrinogen molecules. Such high selective affinity for fibrin(ogen) provides the reaction specificity in a complex tissue fluid milieu and governs the kinetics of fibrinolysis. Any agents that interfere with such binding reactions, e.g., autoantibodies, may also affect the fibrinolytic reactions. Understanding these unique biochemical controls of factors involved in fibrinolysis may provide an insight into the complex regulatory process of extravascular fibrinolysis.

Endotoxemia and intestinal mucosal dysfunction after the relief of obstructive jaundice by internal and external drainage in rats.

We studied the effects of external and internal biliary drainage on the development of endotoxemia in a rat model of obstructive jaundice. Male Donryu rats were allocated to four groups: sham operation, common hepatic bile duct ligation (BDL), internal or external biliary drainage after BDL, and biliary drainage after BDL with oral endotoxin administration. Portal and systemic blood endotoxin concentrations were measured and the histomorphology of the intestinal mucosa was examined. Portal endotoxemia was observed 7 days after BDL and both portal and systemic endotoxemia were observed after 14 days. Portal endotoxemia was reversed by both internal and external biliary drainage and systemic endotoxemia was prevented. The ratio of villous height to crypt depth in the mucosa of the terminal ileum was decreased in rats with external drainage. Oral administration of endotoxin induced marked disruption of the mucosal epithelium in rats with external biliary drainage, but not in rats with internal biliary drainage. Significant increases in portal and systemic blood endotoxin concentrations were observed only in the external drainage group after oral endotoxin administration. The relief of biliary obstruction effectively relieved portal endotoxemia. External biliary drainage, however, has the potentially deleterious effect of disrupting the intestinal mucosa, which may promote the development of endotoxemia. These findings have implications for the use of biliary drainage procedures to reduce postoperative complications in jaundiced patients.

Carcinoembryonic antigen (CEA) and CEA-related substances in the bile of patients with biliary diseases.

The levels of carcinoembryonic antigen (CEA) in the bile of 10 patients with biliary cancer and 9 patients with cholelithiasis were examined immunochemically by the Western blot analysis. All samples of bile from the patients with biliary cancer showed three bands that corresponded to CEA, nonspecific crossreacting antigen, and biliary glycoprotein 1, respectively. The upper band (CEA) disappeared from the bile of patients who underwent curative operations, but it persisted in the bile of patients who underwent noncurative operations. All samples of bile from the patients with cholelithiasis did not show the upper band (CEA), even in those samples that had high levels of CEA by the conventional enzyme immunoassay. We suggest that, in order to diagnose the presence of tumor, to assess the therapeutic efficacy of surgery, and to detect any residual tumor, not only should the level of bile CEA be measured but also a Western blot analysis of the bile should be performed since it is more reliable.

Superficial spreading type extrahepatic bile duct cancer with lymphatic micrometastasis: report of a case.

We report herein the case of a 69-year-old woman with extrahepatic bile duct cancer which had developed superficially along the ductal mucosa without penetrating the fibromuscularis. She underwent a pancreatoduodenectomy; however, micrometastases were found histologically in the regional lymph nodes and she died with involved para-aortic lymph nodes and bone metastases 14 months after the operation.

Effect of activated protein C on impaired fibrinolysis in rats with obstructive jaundice.

We studied the effect of activated protein C (APC) on impaired fibrinolysis using a rat model in which disseminated intravascular coagulation (DIC) is induced by the intravenous injection of endotoxin in rats with obstructive jaundice. An intravenous injection of endotoxin in rats with obstructive jaundice resulted in pulmonary hemorrhages and a marked increase in the plasma levels of tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor activity. Prophylaxis with APC before the injection of endotoxin resulted in a decrease of the number of lung hemorrhages and an accelerated release of t-PA antigen. Thus, DIC in obstructive jaundice may be due to impairment of fibrinolysis and an increased susceptibility of endothelial cells to endotoxin. APC may be effective as a treatment for patients with obstructive jaundice associated with DIC.

[A case of gastric cancer with multiple liver metastasis treated with transarterial and transportal chemoembolization of tegafur/lipiodol and epirubicin].

A 56-year-old woman was admitted for advanced gastric cancer (S3H3N3P2 Stage IV). She underwent subtotal gastrectomy, left ovariectomy, and catheterization of the hepatic artery. Pre- and postoperative adjuvant chemotherapies consisting of tegafur, epirubicin, mitomycin C and cisplatin were performed. Two months after surgery, combination of transhepatic arterial and transportal chemoembolization with tegafur 400 mg/lipiodol 3 ml and epirubicin 20 mg was especially effective for this patient. The metastatic lesions of the liver regressed by 85% on computed tomography and the CEA level in the plasma decreased from 51.3 to 5.1 ng/ml. The response was judged partial response (PR), and the patient is now in good general condition.

Surgical indication and significance of portal vein resection in biliary and pancreatic cancer.

Tumor and vascular resection was carried out in 27 patients with biliary and pancreatic cancer. Vascular resection included resection and reconstruction of the both the portal vein and hepatic artery in two of the patients. Portal vein resection only was carried out in 23 patients, and resection of the side wall and plasty of the portal vein was carried out in the other two patients. The technical limit of portal vein resection without graft was 4 cm in the hepatic hilus and 7 cm after total pancreatectomy or pancreatoduodenectomy without grafts. On temporary occlusion of the portal vein between resection and reconstruction, simple occlusion was sufficient if it occurred within 30 minutes. In occlusion of more than 30 minutes, simultaneous occlusion of the superior mesenteric artery is better to prevent congestion of the intestine. If occlusion of more than 60 minutes is anticipated, a bypass between the superior mesenteric vein and the femoral vein with Anthron tube is recommended. The postoperative course was uneventful in 20 of the 27 patients. Two patients died within 1 month after surgery. The mortality rate for this aggressive surgery was 8.4%. Minor complications such as hydrothorax, small bile leakage, and localized abscess were observed but soon subsided in five patients. Fourteen of 27 patients survived or are alive after more than 1 year, and 9 of 14 patients survived or are alive after 2 years. Forty-seven percent of the patients who had no lymph node metastasis or peritumor lymph node metastasis without cancerous invasion of the portal vein intima survived more than 2 years. The longest length of survival of a patient with nonfunctioning islet cell carcinoma of the pancreatic head was 5 years 9 months. The longest surviving patient with ductal cell carcinoma of the pancreas is still living after 4 years. This approach is recommended in certain patients with vascular involvement but without lymph node metastasis or those patients with only peritumor lymph node involvement. Frozen section of mesenteric and paraaortic nodes should be standard practice before this aggressive resection.

Endotoxin-induced lung hemorrhages in obstructive jaundiced rats.

Endotoxemia in patients with biliary obstruction contributes to the high morbidity and mortality rates following surgery. We developed an animal model of disseminated intravascular coagulation (DIC) in rats on which bile duct ligation was performed following an injection of endotoxin (200 micrograms/kg bw). Macroscopic hemorrhages and microthrombi in the lung were found in jaundiced rats 6 hours after the injection of endotoxin and yet these phenomena were not found in non-jaundiced rats following an injection of the same amount of endotoxin. Coagulation studies also revealed characteristic findings of DIC in the jaundiced rats following the injection of endotoxin. This study confirms that obstructive jaundice is one of the main predisposing factors in the course of endotoxin-induced DIC.

Interaction of fibrinogen with murine melanoma cells: covalent association with cell membranes and protection against recognition by lymphokine-activated killer cells.

B16/F10 melanoma cells, in a medium containing fibrinogen, form a coating of fibrin(ogen) on their surfaces. This coating is cross-linked in a manner characteristic of catalysis by cellular transglutaminase. The fibrin(ogen) coating on the surface of these tumor cells provides protection against the lytic effect of autologous lymphokine-activated killer cells.

Combination of intraoperative radiation with resection of cancer of the pancreas.

The utility of intraoperative radiation therapy (IORT) as an adjuvant to the surgical resection of pancreatic cancer was studied. In 1976, as our first trial with this combined therapy, we applied IORT with 30 Gy of electron beam with 8 MeV to 15 patients to prevent local recurrence around the celiac axis and superior mesenteric artery after standard pancreatectomy. However, the combined therapy did not show an improvement in survival rate as compared to that of 19 patients with standard operation alone. Autopsies of three patients with the combined therapy did not show involved lymph nodes in the radiation field, but did show local recurrence around the aorta outside the radiation field. By comparison, we performed extended operation without IORT on nine patients, with almost complete dissection of the lymph nodes around the aorta, from the diaphragm to the level of the inferior mesenteric artery. This extended surgery did not improve survival time, and autopsy showed local recurrence in spite of the dissection of lymph nodes. Therefore, since 1984, we have performed IORT with a dose of 30 Gy, 9 MeV, and an extended radiation field from the diaphragm above to the inferior mesenteric artery below, following extended operation on 14 patients. The five-year cumulative survival rate of these cases was 33.3%. Four autopsies showed improvement of local control rate. No radiation-related complications were noticed postoperatively in patients who underwent extended IORT following pancreatectomy. We were encouraged to continue this approach for the cure of pancreatic cancer.

[Surgical treatment of chronic pancreatitis without pancreatic duct dilation].

In 11 patients with chronic pancreatitis without dilation of the main pancreatic duct, 4 had segmental lesions of the pancreas and 7 had diffuse lesions of the pancreas. Patients with the segmental lesion had a relatively good pancreatic function and were relieved from pain by surgical treatment for the segmental lesion. On the other hand, patients with the diffuse lesion had far advanced dysfunction of the pancreas and were not improved by drainage operation of the pancreatic duct. For such cases, total or near total pancreatectomy has been indicated to relieve pain at the price of creating insulin dependent diabetes. To control pain and to reserve pancreatic function as long as possible in these cases, we performed the resection of all the pancreatic nervous plexus for such 3 patients and have obtained good results, although follow-up periods are still short. This new approach may offer a means of relieving pain with preservation of endocrine function in selected patients with chronic pancreatitis, especially in patients who have not dilated pancreatic duct.

Biosynthesis of various types of collagen by human hepatoma cells in vitro.

A cloned human hepatoma cell line (HH2-1) produced and formed collagen fibers in vitro. The relative rate of collagen synthesis by the cells was increased with an enhancement of the cell density. An analysis of the components of the collagen using sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the cells synthesized interstitial collagen, types I and III, and other collagenous proteins. Thus, human hepatoma cells may play an important role in the formation of stromal collagen in the tumor.

Facial nerve neurinoma: two cases located in the horizontal portion.

Two small facial neurinomas located in the horizontal portion were presented to demonstrate the clinical features, diagnostic evaluation, and surgical treatment. These two cases show the early state of facial neurinoma and suggest the mechanism of facial paralysis by facial neurinoma. Facial nerve decompression is recommended for Bell's palsy unresponsive to the conservative therapy and recurrent facial palsy.

Immunohistochemical localization of collagens in the ear.

The aim of this work was to prepare specific antibodies to various types of collagen in order to study on immunohistological localization of collagen under normal and pathologic conditions. Human type I and III collagens were extracted from human dura mater and placenta using limited pepsin digestion followed by differential salt precipitation and chromatographic purification. The purity of collagens was assessed by SDS polyacrylamide gel electrophoresis. Antibodies to type I and III were prepared in rabbits, and showed a high reaction with the corresponding human collagens, and these antibodies were tested to determine activity using ELISA. However, antibody to type I also showed some cross-reaction with type III, and antibody to type III, with type I. Using these antibodies, tissue distribution of collagen was examined in the middle ear by peroxidase anti-peroxidase method. In granulation tissue, it was revealed that types I and III co-existed.

Variations in 5'-nucleotidase activity in established mesenchymal cell lines from syngeneic A/J mice.

5'-Nucleotidase activity was analyzed in four different mesenchymal cell lines (F, m, e and SP) established from syngeneic A/J mice. The 5'-nucleotidase activity of fibroblasts was lower in transformed cells (F and m) than in nontransformed cells (e). An increase in cell contact during confluence or during high cell density increased 5'-nucleotidase activity, and a decrease in cell contact caused a decrease in 5'-nucleotidase activity in both fibroblastic (F, m and e) and reticulum (SP) cell lines. These results are evidence that 5'-nucleotidase activity in mesenchymal cells is influenced by intercellular contact as well as transformation.