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We report a rare case of chronic expanding hematoma of thorax extended to the neck. An 83-year-old man with a history of Lucite ball plombage and thoracoplasty of bilateral thorax was admitted with numbness of left upper extremity. In 6 months, left supraclavicular fossa was gradually bulged like tumor. The lesion was diagnosed as chronic expanding hematoma. Surgically, Lucite balls were removed with surrounding hematoma debris and fluid, and neck hematoma, which was slightly communicated to the thorax, was extirpated. We discussed the genesis of this hematoma and its extension to the neck.

Summary Objective In the present study, we investigated the relationship between the urinary excretion rate of the oxidized nucleoside 8-hydroxydeoxyguanosine (8-OHdG) and clinical factors in lung cancer patients. Methods The present study included 100 patients, who underwent a lung surgery. The patients included 62 men and 38 women with a mean age of 65.5 years ranging from 35 to 82. The diagnosis included 81 primary lung cancers, 9 metastatic lung cancers and 10 benign lung diseases. Urine samples collected for 24 h were analyzed for the content of 8-OHdG using an ELISA assay. Results The urinary excretion rate of 8-OHdG in smokers was significantly higher than that in never-smokers. Specifically, the 8-OHdG excretion rate of current smokers was higher than that of patients who had quit smoking for longer than 1 month. Excluding current smokers, the urinary excretion rate of 8-OHdG did not relate to age or gender, but to the malignant potential of the disease. The urinary 8-OHdG level increased in the order of metastatic lung cancer, primary lung cancer and benign disease. In lung cancer patients, furthermore, the mean urinary 8-OHdG level of patients with stages II–IV disease was significantly lower than that of patients with stage I disease. Conclusions Smoking significantly increased the urinary excretion rate of 8-OHdG, suggesting that smoking causes an increased rate of oxidative DNA modifications. On the other hand, the capacity to repair oxidative DNA modifications might be impaired to some extent in cancer patients.

Objective— To assess the expression and distribution of a neurotrophic/antiangiogenic factor, pigment epithelium-derived factor (PEDF), related to angiogenesis that is a possibly key event during atherogenesis in human atherosclerotic plaques. Methods and Results— Twenty fresh aortic samples were used for reverse-transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry (IHC). In addition, 80 stocked paraffin blocks of coronary arteries from 40 autopsy cases were also used. IHC revealed divergent staining patterns for PEDF in both the aortas and the coronary arteries tested, ie, “cytoplasmic staining” or “extracellular deposition,” were observed, respectively. In the areas showing cytoplasmic staining, double PEDF was expressed in a majority of the foamy macrophages and in some smooth muscle cells, and the PEDF-positive cell frequency was positively correlated with that of microvessels in a cell-rich area in the coronary arteries ( P P =0.0003). Conclusions— These results suggest that PEDF may function as an antiangiogenic factor when it is deposited onto the extracellular matrix. Thus, PEDF may play a significant role in determining the balance of angiogenesis/ antiangiogenesis during atherogenesis.

Chronic expanding hematoma of the thorax is a rare disease. We report a 60-year-old man with chronic expanding hematoma, which occupied the left entire hemithorax. Its hematoma was extirpated with pleuropneumonectomy. It was performed through posterolateral thoracotomy following median sternotomy, through which left hilar structure including inferior pulmonary vein could be accessed and closed. After the operation, he was discharged without any significant complications.

The aim of the current study was to determine the nvolvement of ABO blood group in clinicopathologic features in squamous cell carcinoma (SCC) of the esophagus, that has not previously been studied fully. Two hundred and eighty four consecutive patients with esophageal SCC were enrolled for the study. The relationship between patients' ABO blood group and the clinicopathologic features was analyzed. The proportion of poorly differentiated SCC among patients with blood group O was significantly lower than in those patients with other blood types (P = 0.001). The mean size of the tumors in patients with blood group AB was significantly larger than those in patients with other blood groups. The proportion of tumors associated with venous invasion was significantly higher in patients with blood type A than those of tumors in other blood types (P = 0.007). The TNM stages of tumors in blood group AB were found to be significantly more advanced (P = 0.036) than other groups. The functional significance of ABO blood group distribution might be associated with biological behavior of SCCs. However, it was found not to be a clinical predictor for the prognosis of the patients with esophageal SCC.

We analysed data on 1117 patients with gastric cancer who were treated by curative resection. Attention was focused on invasion and a recurrence of the cancer. Based on a univariate analysis, death following a recurrence and prognosis were related to age of the patients, size of the tumour, tumour location, tumour tissue differentiation, growth pattern, depth of invasion, lymphatic and vascular invasion and lymph node metastasis. In proportion to the growth potential, determined by the level of proliferating cell nuclear antigen (PCNA) labelling, the death related to a recurrence was increased and the prognosis was poorer. Multivariate analysis showed that the three factors of serosal invasion, PCNA labelling index and lymph node dissection were independent prognostic factors. When sites of recurrence were analysed regarding each depth of invasion, haematogenous recurrence, in particular in the liver, occurred even in cases of an early invasion and many types of recurrences, including peritoneal recurrence, were noted in patients with an advanced state of invasion.

Direct evidence of tumour seeding in distant organs at the time of surgery for gastric cancer is not available. An immunocytochemical assay for epithelial cytokeratin protein may fill this gap since it is a feature of epithelial cells that would not normally be present in bone marrow. The bone marrow of 46 patients with primary gastric cancer was examined for tumour cells, using immunocytochemical techniques and antibody reacting with cytokeratin, a component of the intracytoplasmic network of intermediate filaments. The monoclonal antibody CK2 recognises a single cytokeratin polypeptide (human cytokeratin no. 18) commonly present in epithelial cells. The expression of tumour-suppressor genes p53 and RB for the primary lesion was also determined using the monoclonal antibodies PAb 1801 and 3H9 respectively, and the proliferating activity was determined by the Ki-67 antigen labelling index for MIB-1 antibody staining. Of these 46 patients, 15 (32.6%) presented with cytokeratin-positive cells at the time of primary surgery. The positive findings were related to the undifferentiated tissue type and to the prominent depth of invasion, but not to other clinicopathological factors. In 2 of 15 (13.3%) patients, the depth of invasion was limited to the mucosa. The metastatic potential to bone marrow did not relate to expressions of p53 and RB genes, or to the proliferating activity of MIB-1 staining for the primary lesion of gastric cancer. As tumour cells in bone marrow are indicative of the general disseminative capability of an individual tumour, this technique may be useful for identifying patients at high risk of metastasis from a gastric tumour. Images Figure 1

We have found that elevation of preoperative serum sialyl-Tn antigen (STN) levels is associated with a poor prognosis for gastric cancer patients, and these high levels remain in the advanced stage of the disease. We have now examined findings with the combined assay of STN and carcinoembryonic antigen (CEA) levels with regard to prediction of the prognosis of gastric cancer patients. Serum CEA levels and STN levels were determined preoperatively in 349 Japanese patients with gastric cancer. The patients were divided into four groups: (A) the CEA (-) STN (-) group (CEA < or = 5 ng ml-1, STN < or = 45 U ml-1, n = 286); (B) the CEA (-) STN (+) group (CEA < or = 5 ng ml-1, STN > 45 U ml-1, n = 31); (C) the CEA (+) STN (-) group (CEA > 5 ng ml-1, STN < or = 45 U ml-1, n = 17); and (D) the CEA (+) STN (+) group (CEA > 5 ng ml-1, STN > 45 U ml-1, n = 15). Clinicopathological features and the prognosis of these groups were examined. The distribution of two markers showed no significant correlation. The patients in the CEA (+) STN (+) group (group D) had more advanced disease than the patients in CEA (-) STN (-) group (group A); tumour size was larger, serosal invasion was prominent, lymphatic and vascular involvement was frequent and the tumour was more infiltrative. Lymph node metastasis and hepatic metastasis were more common. Total gastrectomy was usually performed, and the non-curative rate was higher. The 5-year survival of patients in the CEA (+) STN (+) (group D) was 14.5 +/- 9.5%, that is lower than that of patients in any other group [CEA (+) STN (-) (group C) 44.1 +/- 12.7% (P < 0.05); CEA (-) STN (+) (group B) 60.1 +/- 9.5% (P > 0.05); CEA (-) STN (-) (group A) 77.6 +/- 9.5% (P < 0.05)]. This combined assay of these markers will aid in estimating the prognosis and selecting appropriate drugs and care for gastric cancer patients.

Proliferative activities in 181 primary Borrmann type 4 gastric carcinomas were investigated using percentage labelling of proliferating cell nuclear antigen (PCNA) and an argyrophilic nucleolar organiser region (AgNOR) count. Tumours with a high proliferative activity often metastasised to lymph nodes (P < 0.01), and these patients had a lower survival rate (P < 0.05). A significant correlation was recognised between the PCNA labelling percentage and AgNOR count (r = 0.452, P < 0.001). Cox's regression analysis showed that PCNA labelling percentage is an independent prognostic factor. These results indicate that estimating proliferative activity may be useful in predicting lymph node metastasis and patients' prognosis in cases of Borrmann type 4 gastric carcinoma. Images Figure 1

The effects of heat on intracellular accumulation of anthracyclines were investigated by laser flow cytometry analysis. Sarcoma-180 cells were exposed to Adriamycin (ADM), epirubicin (EPIR), daunomycin (DM), THP-Adriamycin (THP), ME-2303 (ME) and KRN-8602 (KRN) at 37 degrees C and at higher temperatures. There was a dose-dependent increase in the fluorescence intensity of all drugs at 37 degrees C, but heat varied the fluorescence intensity of each drug. At 43 degrees C the cellular fluorescence of ADM and EPIR increased by approximately 200%, but for DM the increase was 110-130%. The cellular fluorescence of THP and ME was little affected by heat, and heat reduced that of KRN to 80-90%. Each drug showed was unique in the relationship between drug exposure time and the fluorescence intensity at 37 degrees C and 43 degrees C. Cytotoxicity determined by the MTT assay was enhanced with heat in the cases of ADM and EPIR, but not with DM, THP, ME, or KRN. Thus, ADM and EPIR are expected to show enhanced antitumor activities when given in combination with hyperthermia.

We treated a 27-year-old pregnant woman with Borrmann type IV gastric cancer and immunohistochemically detected micrometastasis of cancer cells in the bone marrow. Total gastrectomy combined with splenectomy was followed by postoperative chemotherapy. Despite intensive treatment, she died with tumor progression 6 months later. When malignant cells are present in the bone marrow, the prognosis is poor. The literature on gastric cancer associated pregnancy is reviewed.

Eighty-five patients with gastric cancer invading the serosa following curative resection were analyzed with respect to clinicopathological features and prognosis by staining the argyrophilic nucleolar organizer region (AgNOR). The AgNOR was counted in 200 cancer cells per tissue and the mean number per cell was identified as the AgNOR score. The AgNOR count varied from 1.79 to 5.71, while the mean value was 2.92 +/- 0.74 and the median score was 2.95. The patients were divided into two groups: the AgNOR high group (AgNOR count greater-than-or-equal-to 2.95, n=44) and the AgNOR low group (AgNOR count < 2.95, n=41). There were no differences between the two groups with respect to sex, age, tumor size, location of the tumor, macroscopic appearance, histological differentiation, growth pattern and vascular involvement. The lymphatic advancement of tumor cells was prominent and the rate of lymph node metastasis was higher (p

In an attempts to increase the antitumor effect and to reduce normal tissue toxicity, the combined cytotoxic effect of cis-Diamminedichloroplatinum (II) (CDDP) and cis-diammine(1,1-cyclobutane dicarboxylate) platinum (II) (CBDCA) was investigated using HeLa and colon 26 cell lines and the combination index (CI). Cytotoxicity of the combination of CDDP and CBDCA on 27 surgically resected specimens of human gastric and colorectal adenocarcinomas was also evaluated using the in vitro succinate dehydrogenase inhibition (SDI) test. The CI values varied with the dose ratio examined (1:1-1:6) of CDDP and CBDCA, with findings that CI1, synergy, was obtained at fraction affected (Fa)0.75 for HeLa cells and at Fa0.9 for colon 26 cells in cases of a dose ratio of 1:1 to 1:2. Of all 27 clinical human adenocarcinomas, the succinate dehydrogenase (SD) activity was significantly lower in cancer cells concomitantly exposed to both CDDP and CBDCA than in those exposed to either drug alone. These positive effects of a combination of two platinum analogues on human malignant tissues have heretofore not been reported, which would warrant the clinical application of this combination for human malignant tumors.

Overexpression of the tumour suppressor gene p53 was investigated immunohistochemically in 96 primary gastric carcinomas and 26 corresponding metastatic perigastric lymph nodes. Abnormalities in p53 expression were found in 52 (54%) of the 96 primary carcinomas. Tumours stained positively for p53 frequently metastasised to lymph nodes (the metastatic rate: 85%) compared to findings in those with negative p53 staining (64%, P < 0.05). Ninety-two percent (24/26) of the malignant cells in the lymph nodes stained positively for p53. When the DNA ploidy pattern of the tumour was determined by flow cytometry, the aneuploid tumours in p53 positive and negative groups accounted for 69% and 45%, respectively (P < 0.05). Proliferative activity of the tumour, as measured by Ki-67 labelling, was significantly higher (30.6 +/- 12.0%) in the p53 positive group than that (25.1 +/- 10.7%) in the p53 negative group (P < 0.05). Thus, gastric cancer with a mutant p53 has high proliferative activity and metastasis to lymph nodes will probably occur. Images Figure 1

Alcaligenes faecalis 菌体外に分泌するポリエステル分解酵素[P(3HB)デポリメラーゼ] を用いて,種々の分子構造をもつ11種類のポリエステルについて酵素分解実験を行い,酵素分解速度におよぼすポリエステルの分子構造の影響について調べた。ポリエステルには,ポリ[(R)-3-ヒドロキシブチラートコ(1),ポリ[(3)-3-ヒドロキシブチラート](2),アタクチック構造のポリ[(R,S)-3-ヒドロキシブチラート](3),ポリ[(R)-3-ヒドロキシバレラート](4),ポリ[3-ヒドロキシプロピオナート](5),ポリ[(R)-2-ヒドロキシプロピオナート](6),ポリ(4-ヒドロキシブチラート)(7),ポリ(5-ヒドロキシバレラート(8),ポリ(6-ヒドロキシヘキサノアート)(9),ポリ(エチレソアジペート)(10)およびポリ(1 ,4ブチレンアジペート)(11)を用い,酵素分解反応を37℃,7pH7.4のリン酸緩衝液中で行った。酵素の分解速度は,次の序列で低下した。(1)=(5)>(10)>(3)>(4)=(7)>(2)=(6)=(8)=(9)=(11)=0ポリエステルの分子構造と酵素分解速度との相関性について議論した。

Relationships between in vitro chemosensitivity and cell nuclear DNA content were investigated in malignant cells from 41 patients exhibiting advanced gastric carcinoma. The chemosensitivity was evaluated by measuring the succinate dehydrogenase (SD) activity in drug-exposed cancer cells and the DNA content was microspectrophotometrically determined. Following exposure of malignant tissue to carboquone (CQ) and cisplatin (DDP), the mean SD activity in cells displaying a relatively regular DNA distribution (type II) was significantly higher than that in those exhibiting a widely scattered DNA distribution (type IV; P less than 0.01 in CQ, P less than 0.05 in DDP). A similar tendency was recognized in cells that were treated with aclacinomycin A (ACR), Adriamycin (ADM), and mitomycin C (MMC). Such a decrease in SD activity in cells exhibiting a type IV pattern was remarkable, especially in cases undifferentiated adenocarcinoma. Mitotic counting analysis revealed a significantly higher value for DNA pattern type IV as compared with the findings for type II (P less than 0.01). These results demonstrate that gastric carcinoma displaying a high malignant potentially shows a better response to antitumor drugs. Adjuvant chemotherapy prescribed following drug-sensitivity testing should be effective against such tumors.

Gene transfer to vein grafts has therapeutic potential to prevent late graft failure; however, certain issues, including efficacy and safety, have hindered the clinical application of this treatment modality. Here, we report the successful and efficient gene transfer of plasmid DNA via ex vivo electroporation into veins as well as into vein grafts. Two approaches were used: one involved transluminal in situ gene transfer using a T-shaped electrode (the “Lu” method), and the other was an adventitial ex vivo approach using an electroporation cuvette followed by vein grafting (the “Ad” method). The Lu method was carried out at 10 V, with optimal gene transfer efficiency in the in situ jugular veins of rabbits, and transgene expression was observed primarily in endothelial cells. However, when these veins were grafted into the arterial circulation, no luciferase activity was detected; this effect was probably due to the elimination of the gene-transferred cells as a result of endothelial denudation. In contrast, optimal and satisfactory gene transfer was obtained with the vein grafts subjected to the Ad method at 30 V, and transgene expression was seen primarily in adventitial fibroblasts. Gene transfer of endothelial nitric oxide synthase cDNA to the vein graft via the Ad method successfully limited the extent of intimal hyperplasia, even under hyperlipidemic conditions, at 4 wk after grafting. We thus propose that the Ad method via ex vivo electroporation may provide a novel, safe, and clinically available technique for nonviral gene transfer to sufficiently prevent late graft failure.

Significance of extended radical surgical treatment including three-field lymph node dissection for squamous cell carcinoma (SCC) of the esophagus remains debatable. The aim of the current study was to reconsider the merits and demerits obtained by three-field lymph node dissection for esophageal carcinoma and also to attempt to elucidate an appropriate surgical strategy for submucosal SCC of the thoracic esophagus. Thirty-one patients with SCC of the thoracic esophagus who had been treated with esophagectomy and two-field (thoracic and abdominal) lymph node dissection without preoperative therapies were enrolled. Five-year survival rate was 75.0% and the incidence proportion of postoperative complication was 9.7%. These data regarding postoperative outcome of patients were by no means inferior to those in the previous reports referring the prognosis of patients with esophageal carcinoma who had been treated with three-field lymph node dissection. Authors would like to mention that two-field lymph node dissection associated with reduced incidence of postoperative complications might be enough to treat the submucosal SCC of the thoracic esophagus.

Oxidative damage to diverse physiological molecules, including proteins, lipids, and nucleic acids, is an inevitable outcome of various cellular activities in living organisms. In particular, some oxidised forms of nucleotides cause miscoding of genetic information, and have therefore been present as a major threat for cells. Multigene systems to counteract such oxidative damage have evolved in diverse organisms. In E coli , several mutants designated ‘mutator’ have been isolated, and in these cells the mutation rate is significantly elevated, due to disruption of genes regulating the spontaneous mutation rate on the genome. Previous studies using these mutators have identified three genes that function in the system to counteract mutagenic oxidative damage. The mutT− strain is one of the mutators that exhibit the highest spontaneous mutation rate. Maki H et al have shown that the product of the mutT gene hydrolyses an oxidised form of guanine nucleotides, 8-oxo-2′-deoxyguanosine 5′-triphosphate (8-oxo-dGTP).1 8-oxo-dGTP incorporated into the genome stably pairs with adenine as well as cytosine in the template strand, accumulation of this oxidised form of guanine nucleotides leads to an increase in base substitution mutations—that is, A:T to G:C and G:C to T:A transversions. In the mutT− strain, the rate for A:T to C:G transversion is indeed elevated 1000 fold over the wild type level.2 The other two genes that function in cooperation with mutT are mutM (fpg) and mutY , both of which encode a DNA glycosylase to excise deleterious bases on the genome.3 The former excises 8-oxo-guanine in the opposite site of cytosine on the genome, the latter removing adenine that pairs with 8-oxo-guanine. Thus, even in cells lacking MUT , G:C to T:A transversions are suppressed low.4 Multiplicity of cellular anti-mutagenic systems guarantees the spontaneous mutation rate on the genome at an extremely low …

G2/M cyclins including cyclins A and B can exert their biologic functions of mitosis and proliferation of the tumor cells by being combined by protein kinase p34cdc2. The aim of the current study was to elucidate the clinicopathologic significance of immunohistochemical expression of p34(cdc2) in esophageal squamous cell carcinoma (ESCC), which has not been resolved.Immunohistochemical expression of p34(cdc2) was examined for 91 cases of ESCC, and the relationship between the type of p34(cdc2) expression and the clinicopathologic features of the patients and tumors was analyzed.Forty-one ESCCs demonstrated cytoplasm dominant expression of p34(cdc2) and the other 50 ESCCs showed nuclei dominant p34(cdc2) expression. This differential expression pattern of p34(cdc2) did not reflect a prognostic aspect; however, the proportion of keratinizing tumors ESCCs with cytoplasm dominant expression of p34(cdc2) was significantly higher than that among ESCCs presenting nuclei-dominant p34(cdc2) expression (P=0.006).Cellular differentiation in squamous cell carcinoma of the esophagus may be mediated by an intracellular localization of p34(cdc2).

A total of 195 patients with node-positive gastric carcinoma who were treated by curative gastrectomy and lymphadenectomy were studied to evaluate the prognostic significance of the number of metastatic lymph nodes. Univariate analysis showed that the number and level of positive nodes, tumour size and depth of invasion, and type of gastrectomy were significantly related to patient survival. Multivariate analysis indicated that the number of positive nodes (up to six versus seven or more; relative risk 2.91), depth of invasion (three levels; relative risk 1.83) and histological type (well versus poorly differentiated; relative risk 0.63) were independently correlated with survival. The results indicate that the total number of positive nodes is the most significant prognostic factor in patients with node-positive gastric carcinoma.

A time trend for characteristics and prognoses of patients with non-small cell lung cancer (NSCLC) who underwent surgical resection was investigated.A series of 1123 consecutive patients with NSCLC who underwent surgical resection from 1975 to 1998 was reviewed with respect to changes in patient profile and surgical outcome among subgroups classified by clinicopathologic factors.With time, the proportion of female, elderly (or =70 years), pathologic stage IA, nonsmoking, and adenocarcinoma patients increased significantly whereas pneumonectomy, incomplete resection, and pathologic stage IIIA patients decreased significantly. Overall survival showed an upward trend with 5-year survival rates of 30.0% in the 1970s, 41.6% in the 1980s, and 50.1% in the 1990s (P.0001). This tendency was similar in every pathologic stage that was observed. The proportion of female patients with adenocarcinoma that exhibited the most favorable prognosis among subpopulations classified by gender and cell types was significantly higher in the 1990s (28.0%) than in the 1970s (14.0%). Multivariate analysis revealed that female gender, adenocarcinoma, complete resection, and early pathologic stage were independently favorable factors whereas advanced age was an unfavorable factor.The improved survival following surgical resection for NSCLC during the study period was associated with an increasing population of female patients with adenocarcinoma, more detection of early disease, and effective elimination of unresectable cases.

The expression or activity of manganese superoxide dismutase (Mn-SOD) is reduced in a variety of malignant tumors and Mn-SOD may act as a new type of tumor suppressor gene. On the other hand, increased expression of Mn-SOD can diminish the cytotoxic effects of several anticancer modalities, including tumor necrosis factor alpha, ionizing radiation, certain chemotherapeutic agents and hyperthermia. Although Mn-SOD expression and its role in various cancers are intensely studied, little is known about its function in gastrointestinal carcinomas. To examine the expression level and significance of Mn-SOD in gastrointestinal carcinomas, Mn-SOD mRNA expression was examined in 53 gastric carcinoma and 38 colorectal carcinoma by reverse transcription-polymerase chain reaction and was compared with those in the corresponding normal mucosal tissues. The tumor/normal (T/N) ratio was calculated and the data were clinicopathologically analyzed. The average T/N ratios of Mn-SOD mRNA expression in gastric and colorectal carcinomas were 2.19 and 3. 72, respectively. Clinicopathologic analyses revealed positive correlation between the Mn-SOD expression level and venous invasion in both gastric and colorectal carcinomas (p

We examined the dThdPase activity in primary gastric cancer and metastatic lymph nodes from human subjects. The dThdPase activities were significantly higher in primary tumors than in the normal gastric wall, particularly in the center of the tumor rather than in the periphery (P

Angiogenesis has an important role in the growth and metastasis of solid tumors. Several angiogenic factors have been identified, one being platelet-derived endothelial cell growth factor (PD-ECGF), which is identical to thymidine phosphorylase (dThdPase). We investigated the activity of dThdPase in 84 samples of 42 human gastric cancers, by liquid chromatography. The dThdPase activity significantly correlated to the microvessel density assessed by immunostaining to CD-31 antigen (P

We compared the survival between 46 patients with hereditary nonpolyposis colorectal cancer (HNPCC) and 1185 cases with sporadic colorectal cancer, who underwent a resection for the disease between 1972 and 1995. In a univariate analysis, the survival correlated well with stage, curability, size and the presence of HNPCC. Patients with HNPCC had a longer survival than those with sporadic colorectal cancer (P=0.0277). A multivariate analysis suggested that stage, curability, age, and HNPCC were the effective combination of factors predictive of survival. The above findings are thus expected to have a major influence on the evaluation of clinical trials in patients with colorectal cancer.

The clinicopathological features and prognosis of gastric cancer in 344 patients aged 70 years or older who underwent gastrectomy between 1965 and 1990 were determined. Over the years the mean size of the tumour decreased, differentiated tumour tissue was more common, depth of penetration was less prominent, lymphatic and vascular involvement was less frequent, and the rate of lymph node metastasis and peritoneal dissemination decreased. Extensive lymph node dissection was more frequently carried out and the rate of curative resection rose. Survival rates improved with early detection of gastric cancer and there was no increase in operative morbidity and mortality rates. As age alone is not a contraindication to surgery for patients with gastric carcinoma, early detection of the lesion and surgical treatment are expected to increase the survival of elderly patients with this malignancy.

We report on a case of multiple bone metastasis and disseminated intravascular coagulation (DIG) in a 49-year-old Japanese man. He underwent total gastrectomy for advanced gastric cancer in July 1992, He was diagnosed as a case of multiple bone metastasis in August 1993. Severe anemia, thrombocytopenia, and elevated fibrinogen degradative products were indicative of DIG. He was treated with sequential i.v. administration of methotrexate (MTX) and 5-fluorouracil (5-FU) and continuous i.v. infusion of heparin and gabexate mesilate. After two weeks of treatment with MTX combined with 5-FU, the findings of DIC disappeared and his general condition improved dramatically.

From 1965 to 1987, 126 patients who had gastric cancer invading the muscularis propria (pm) were treated with curative resection in the Department of Surgery II, Kyushu University. We examined the correlation between the proliferating activity of the tumor by staining the tissue for proliferating cell nuclear antigen (PCNA) and the occurrence of lymph node metastasis present in 46.8% (59/126) of the patients. Undifferentiated carcinoma was more frequent in these patients and lymphatic and vascular involvement was prominent. Patients with a lymph node metastasis had a higher level of PCNA staining in the tumors than did those without lymph node metastasis (labeling index: 36.5 +/- 9.6% vs. 25.3 +/- 8.3%) (P < 0.01). The survival rate for patients with lymph node metastasis was lower than that for those without this metastasis (P < 0.01). The 10-year survival rate was 63.6% for the patients with lymph node metastasis and 86.8% for those without lymph node metastasis. Thus, the presence of lymph node metastasis is associated with a high growth potential of tumor cells in pm gastric cancer. Close follow-up and adjuvant chemotherapy in the postoperative period is recommended for these patients.

To clarify the effect of L-histidinol on hyperthermic killing of cells, HeLa and mouse sarcoma-180 (S-180) cells were exposed to heat in vitro in the presence of L-histidinol and the clonogenic surviving fraction of the cells was examined. After pretreating the cells with L-histidinol for 4 h, exposure of the cells to the combination of heat at 43-degrees-C and L-histidinol for various times (30 min to 4 h) reduced the surviving fraction more prominently than heat alone. Optimal concentrations to confer effective enhancement of heat on HeLa and S-180 cells were 9 mM and 3 mM, respectively. Those concentrations showed little toxicity of L-histidinol alone. Enhancement of the effect of heat by L-histidinol was observed only at 43-degrees-C, but not at 41 and 42-degrees-C. Flow cytometric DNA analysis was used to examine the cell cycle transit effect of L-histidinol. L-histidinol alone arrested the HeLa cells in G1-phase. Heat treatment at 43-degrees-C led to an accumulation of the cells in G2/M-phase and a decrease in the G1-phase fraction. The effect of combined treatment with heat and L-histidinol was complementary, in which L-histidinol attenuated the accumulation of the cells in G2/M-phase and prevented a decrease in the G1-phase fraction. Thus, L-histidinol has the capacity to potentiate hyperthermic cell killing in vitro by a mechanism that may be related to the cell cycle transit effect.

We report the late results of resection in 281 patients with gastric carcinoma extending to adjacent organs. In 92 without incurable factors (peritoneal dissemination, liver metastasis and widespread nodal involvement) the 5-year survival rate was 36.7 per cent in those treated by gastrectomy and complete removal of the invaded organ. This value is significantly higher than the 17.4 per cent recorded in those undergoing gastrectomy alone or with incomplete removal of the invaded organs (P < 0.05). In 189 patients with incurable factors, the 5-year survival rates were 5.4 and 2.8 per cent respectively in cases of complete and incomplete excisions. This tendency was similar in patients with a single invaded organ and also in those with plural organ involvement. In potentially curable patients treated by complete excision, the probability of long-term survival was statistically better than that following incomplete excision only when the pancreas was involved (P