Keizo Fujii

Impact of the expression of cyclin-dependent kinase inhibitor p27Kip1 and apoptosis in tumor cells on the overall survival of patients with non–Early stage gastric carcinoma

The expression of p27Kip1 and apoptosis have been implicated in tumor aggressiveness and proved to be prognostic predictors for several human malignancies. In this study, the authors sought to investigate the expression of p27Kip1 and apoptosis and their potential significance in determining the prognosis of patients with non–early stage gastric carcinoma.

Surgery for gastric cancer in patients with cirrhosis

To clarify the therapeutic strategies for gastric cancer surgery in the presence of cirrhosis, 39 patients with gastric cancer accompanied by liver cirrhosis were reviewed. Severe postoperative complications developed in 10 patients (25.6%), and there were 4 (10.3%) hospital deaths, 1 (2.6%) of which occurred within 1 month. Although extended lymph node dissection of D2 or more was adopted for low-risk patients, 3 of 19 patients who underwent such extensive operations, most of which involved complete lymph node dissection in the hepatoduodenal ligament, died. Conversely, only 1 of 20 patients who underwent limited lymph node dissection of D1 or less died. Postoperative massive ascites developed in 6 patients, 3 of whom died. The cumulative 5-year survival rate following curative resection was 63.7% for patients with early gastric cancer, and 13.9% for those with advanced gastric cancer. The most frequent cause of death was cirrhosisrelated, such as hepatic failure or hepatoma. In conclusion, extensive lymph node dissection for patients with gastric cancer accompanied by cirrhosis carried a risk of postoperative fatal massive ascites as lymphorrhea. Thus, lymph node dissection in the hepatoduodenal ligament should be avoided, except in patients with evident metastases, and as a rule, aggressive surgery should not be performed in cirrhotic patients.

Multiple early gastric carcinomas: Clinicopathologic features and histogenesis

Multiple early gastric carcinomas were found in 5–15% of patients with early gastric carcinoma. The goals of this study were to clarify the clinicopathologic features of multiple early gastric carcinomas and to investigate their histogenesis.

Evaluation of Treatment Strategies for Gastric Cancer in the Elderly According to the Number of Abnormal Parameters on Preoperative Examination

The treatment strategies in patients with gastric cancer aged 80 years or older have not yet been well defined. We examined the incidence of postoperative complications and hospital mortality regarding the preoperative condition of such patients. A preoperative examination included evaluations of the cardiac, pulmonary, renal, and hepatic functions, the presence or absence of anemia, nutritional status, and blood sugar content. The incidence of postoperative complications and hospital mortality were then studied in relation to the number of preoperative abnormal parameters. The incidence of postoperative complications was 37.0%. The rate of hospital mortality was 11.1%. Among the patients with abnormalities in five or more items, the incidence of complications was 76.9% and the rate of hospital mortality was 23.1%. In the patients with an operative time of 4h or longer, the same incidence was 71.4%. Among the patients who underwent a curative resection, the 5-year survival rate was 92.3%. For elderly gastric cancer patients with abnormalities in five or more items during a preoperative examination and for those showing a poor level of daily life activity, a less invasive treatment modality should be planned. Patients with abnormalities of four or fewer items at a preoperative examination appear to be good candidates for curative resection.

Calcium concentration in hepatocytes during liver ischaemia-reperfusion injury and the effects of diltiazem and citrate on perfused rat liver.

Objective To clarify the role of the calcium concentration in hepatocytes in liver ischaemia‐reperfusion injury in relation to the protective effect of calcium‐related agents. Design Serial calcium concentrations of extramitochondrial cytosolic sites (EMCa) and in mitochondria (MCa) in hepatocytes of isolated perfused rat liver were measured by an electron probe X‐ray microanalyser, and the effects of calcium‐related agents were evaluated. Methods Ischaemia was induced for 2 h, followed by 2 h of reperfusion in group I (without drug), group II (with diltiazem, 9.3 &mgr;m) and group III (with citrate, 5 mm). Results In group I, EMCa increased rapidly after reperfusion (before ischaemia, 2.0 mmol/kg wet weight; 1 min after reperfusion, 4.4 mmol/kg), and MCa increased (before ischaemia, 2.6 mmol/kg; 1 min after reperfusion, 5.07 mmol/kg). Thereafter the levels decreased, but remained high at 120 min after reperfusion in group I (EMCa, 3.2 mmol/kg, MCa 4.1 mmol/kg). At 1 min after reperfusion, EMCa in group III (2.9 mmol/kg) and MCa in groups II (3.4 mmol/kg) and III (4.0 mmol/kg) were significantly lower than in group I. At 120 min after reperfusion, the EMCa and MCa in groups II (2.5 and 3.1 mmol/kg, respectively) and III (2.4 and 3.0 mmol/kg, respectively) remained at significantly lower levels. Mitochondrial function in groups II and III was better preserved than in group I. The levels of hepatic enzymes in the perfused fluid of group III were lower than in group I. Conclusions Calcium concentration in hepatocytes may play an important role in ischaemia‐reperfusion injury. Diltiazem and citrate demonstrated a protective effect by maintaining a low calcium level in hepatocytes. Eur J Gastroenterol Hepatol 12:291‐297

Significance of proliferating cell nuclear antigen (PCNA) expression in gastric cancer in relation to lymph node metastasis.

Proliferating cell nuclear antigen (PCNA) in gastric cancer was evaluated in relation to lymph node metastasis. A total of 125 gastric cancer patients who underwent gastrectomy were studied immunohistochemically. The PCNA‐positive rate of the primary lesion with lymph node metastasis (47.6%) was significantly higher than that in those without metastasis (24.3%, P < 0.0001). The PCNA‐positive rate of early gastric cancer was significantly higher in lesions with lymph node metastasis (36.9%) than in lesions without lymph node metastasis (14.7%). However, there was no significant difference between lesions with and without lymph node metastasis in advanced gastric cancer. In addition, the PCNA‐positive rate in metastatic lesions (44.6%) was significantly higher than that in the primary lesion (40.0%, P = 0.001). It is concluded that gastric cancer with higher tumor growth activity has a higher rate of lymph node metastasis. Cancer cells in the metastatic foci of lymph node have a higher proliferating activity than that in the primary lesion.

Clinical problems in the surgical treatment of pancreaticobiliary maljunction

The results of surgical treatment of pancreaticobiliary maljunction at our department are described. The 67 patients who underwent surgery for this disease were divided by age into an adult group (45 patients, aged 16 years and over) and a pediatric group (22 patients, aged less than 16 years). The incidence of concomitant carcinoma before surgery and the incidence and severity of postoperative cholangitis were compared between these two groups. In addition, the cell proliferating activity of the biliary tract epithelium in cancer-free patients was compared between the two groups, using the proliferating cell nuclear antigen labeling index (PCNA LI). Ten patients (all adults) were diagnosed with cancer (gallbladder carcinoma in 7 and bile duct carcinoma in 3) before surgery. The surgical techniques used for reconstruction in the cancer-free patients were: in the adult group, hepaticoduodenostomy in 9 patients, Roux-en-Y hepaticojejunostomy in 17, jejunal interposition in 8, and another technique in 1. In the pediatric group, hepatico-duodenostomy was performed in 17 patients. Roux-en-Y hepaticojejunostomy in 3, and jejunal interposition in 2. Postoperative cholangitis occurred in 6 adults (including 2 with severe form) and 1 child (mild case). The PCNA LI of the biliary tract epithelium was high compared to control findings in the biliary tract epithelium of 10 adult patients without pancreaticobiliary maljunction. In the adult group with dilated extrahepatic bile ducts (n=10 examined) this index was 11.4% for the bile duct epithelium (control, 1.5%) and 12.7% for the gallbladder epithelium (control, 1.4%). In the adult group with non-dilated extrahepatic bile ducts (n=5 examined) it was 5.9% for the bile duct epithelium and 13.1% for the gallbladder epithelium. In the pediatric group (n=10 with extrahepatic bile duct dilatation) it was 7.5% for the bile duct and 9.7% for the gallbladder epithelium. (Differences from control values were all significant.) These results suggest that surgery for this disease should be performed as early as possible and that extrahepatic bile duct excision and biliary reconstruction should be performed whether or not extrahepatic bile ducts are dilated.

Clinical Characteristics and Immunohistochemical Examination of Gastric Adenosquamous Carcinoma. Expression of Proliferating Cell Nuclear Antigen(PCNA), Apoptotic Cell, p53, CD44 and Intratumoral Microvessel Density(CD34).

胃腺扁平上皮癌 (以下, 本症) の特徴を検索する目的で, 本症を対象として一般型進行胃癌症例 (以下, 一般型) と比較検討した. まず両者を臨床的に比較し, PCNA, Apoptotic cell, p53, CD44, CD34の発現状態を免疫組織化学的に検討した. 臨床的に本症では肝転移率が高く, Stageの高い症例の多いことが特徴であり, その予後は一般型に比べて有意に不良であった. 本症のPCNA陽性細胞率は一般型に比べて有意に高値であり, Apoptotic Indexは一般型より有意に低率であった. p53, CD44発現陽性率は本症ではいずれも一般型に比べて有意に高率であり, 発現陽性例では両癌成分ともに同等に発現していた. さらに, 腫瘍内血管密度の検索では, 本症は一般型に比べて有意に高値であった. 今回の検討から, 本症は増殖活性が高く, p53などの遺伝子異常が蓄積され, アポトーシス活性が低く, 進展過程で豊富な新生血管が生じて癌細胞が転移しやすい状況を形成している可能性が示唆された.

Surgery for Gastric Cancer Patients Aged 75 and Over

To analyze the clinicopathological characteristics and surgical results in very elderly gastric cancer patients, we reviewed 129 patients aged 75 years and over (group 1) and 708 patients younger than 60 years (group 2) as controls. There were significant differences between group 1 and group 2 with regard to the preoperative impairment of cardiac, respiratory, liver and renal function. The maximum dimension of the tumor in group 1 was greater than that in group 2, and lymph node metastases were more common in group 1. Although reduced lymph node dissection was performed more frequently in group 1 than in group 2, the operative mortality in group 1 (8.5%) was significantly higher than that in group 2 (2.5%, p = 0.002). Among the causes of operative mortality, anastomotic leakage was the most common in the both groups (group 1 36.3%; group 2 44.4%). With regard to the long-term results, although a significant difference in the cumulative 5 -year survival rate was detected in stage I or II patients (group 1 52.2%; group 2 91.1%; p