Ryojin Uchino

Combination of intraoperative radiation with resection of Cancer of the pancreas

SummaryThe 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.

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.

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.

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

SummaryA 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 sulfatepolyacrylamide 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.

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.

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 μg/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.

A Case of Alport-leiomyomatosis Syndrome.

食道の良性腫瘍のうち平滑筋腫が最も多い疾患であるが, 食道全域にわたりその境界が不明瞭なび漫性の平滑筋腫で, 近年1つの独立した症候群として提唱されたAlport-leiomyomatosis症候群の1例を経験したので報告する.症例は23歳の女性で, 昭和60年ごろより嚥下困難と胸部圧迫感を自覚するようになった.平成2年10月に撮影した胸部X線写真で縦隔異常陰影を指摘され, 食道造影像, 胸部computed tomography像およびmagnetic resonance imaging像より胸部食道から胃噴門におよぶび漫型の食道平滑筋腫と診断し手術を行った.手術は食道亜全摘, 胃管による再建を行った.肉眼上食道壁より発生した腫瘤を2カ所認め, 病理組織検査上食道内輪筋由来の平滑筋腫で, 非腫瘤部にも平滑筋腫性病変がみられ, び漫性食道平滑筋腫症と診断した.悪性所見はなかった.本例は陰核肥大やAlport症候群にみられる病変を合併し, Alport-leiomyomatosis症候群と考えられた.