Anergy in patients with leukocytosis

To confirm and clarify a previously found association between anergy and leukocytosis, patients with leukocyte counts above 15,000/mm³ were tested with five intradermal antigens, challenged with dinitrochlorobenzene (DNCB) and croton oil, and their lymphocytes studied in vitro. Of 32 patients with leukocytosis, 8 were unresponsive to all antigens; none of these 8 could be sensitized to DNCB, and only 3 had lymphocytes responsive to phytohemagglutinin. Only one was lymphopenic, and croton oil elicited weak or negative responses in five. Concurrent disease included pancreatitis, pneumonia, sepsis, urinary tract infection, abscess and endocarditis. Although quite ill, none had uremia, known malignancy or miliary tuberculosis, and none was taking immunosuppressive medications. Our evidence suggests that the anergy associated with leukocytosis may be an acute defect in lymphocyte function rather than a transient depression of the inflammatory response, and that leukocytosis may be a common clinically significant cause for depressed delay hypersensitivity in acutely ill patients.     

Multiple primary cancers in patients with gastric cancer

BACKGROUND/AIMS: Some gastric cancer patients have multiple primary cancers (MPC). We evaluate the current status of MPC with gastric cancer. METHODOLOGY: 2,109 gastric cancer patients treated between 1987 and 2002 were analyzed. RESULTS: There were 99 MPC with gastric cancer (4.7%). Second cancer (77.8%) was discovered within 5 years before and after the onset of gastric cancer. 34.3% of patients were discovered within 1 year (synchronous tumor). In the 77 male patients, prostate cancer was the most common occurrence (19.5%), followed by cancers of the colon (18.2%) and liver (14.3%). In the 22 female patients, colon cancer was the most common (31.9%) followed by breast and cervix cancers (22.7%). These cancers were the most common diseases in Taiwan in the same period. Gastric cancer patients with MPC had less stromal reaction and better survival than those without. Patients with metachronous secondary tumors had more peritoneal dissemination and worse survival than those with synchronous primary cancer. CONCLUSIONS: Gastric cancer patients may develop second cancer(s), which is often a current prevalent malignancy. Knowledge of time to development and mode of organ association may allow clinicians to detect potentially curable subsequent cancer(s).     

胃癌患者血清中微小RNA分子的特异性表达及其临床意义

目的 探讨胃癌患者血清中微小RNA(miRNA,miR)的表达差异及其与胃癌发生发展的可能关系.方法 用miRNA芯片分析24例胃癌患者及24例健康人血清样本中miRNA表达谱,并采用实时荧光定量聚合酶链反应(qRT-PCR)对差异表达的miRNA在99例胃癌患者及89例健康人血清中进行大样本验证.最后用TargetScan等生物信息学软件分析所筛选miRNA的靶基因.结果 miRNA表达谱芯片分析发现胃癌患者血清中有29条miRNA的表达水平呈现明显变化.qRT-PCR结果表明在胃癌患者血清中miR-27a、miR-370、miR-491-5p和miR-516-3p的表达水平明显下调.生物信息学分析及文献检索发现miR-27a、miR-370、miR-491-5p和miR-516-3p具有肿瘤抑制因子功能,其表达下调与消化道肿瘤的发生发展密切相关.结论 胃癌患者血清中具有特异性miRNA表达谱,miR-27a、miR-370、miR-491-5p和miR-516-3p的表达下调可能在胃癌发生发展中起着重要作用.     

Serial immunological testing in patients with gastric cancer

Summary Standard immunological parameters measuring non-specific cellular immune reactivity were determined in 175 patients with different stages of gastric cancer prior to surgery and during follow-up. Several tests measuring monocyte activity were also employed. The total number of T cells and their subpopulations T_a and T_29° was unchanged except depression of T_29° in stage IV. The blastogenic response of lymphocytes to PHA as assessed by stimulation of protein synthesis was only depressed in stage IV. In contrast the PHA-induced lymphokine production was increased in all patients but the differences were significant for stage III and IV. Monocyte Fc receptor expression was increased in stages II-IV, while nitro blue tetrazolium reduction and antibody dependent cellular cytotoxicity of monocytes was elevated in stage IV. The number of extractable monocytes was not increased. Longitudinal studies suggested that most of the parameters normalized during follow-up. No major long-term impact of chemoimmunotherapy (5-FU+BCG) on the immune parameters was observed except a transient increase in PPD reactivity approximately 1 year after commencement of treatment. In patients with stage III gastric cancer the increased occurrence of suppressor cells (mostly monocytes) and elevated cytostatic activity of monocytes was associated with a longer survival while the increased lymphokine production and Fc receptor expression were seen in the group of patients succumbing earlier. We concluded that most of the changes in immune parameters were seen only in advanced disease and paradoxically disappeared in the course of disease. The determination of monocyte activity seems to be a sensitive indicator of immune system dearrangements in earlier stages of cancer and a useful prognostic factor in gastric cancer.     

Associated primary tumors in patients with gastric cancer

GOAL: To determine the prevalence of associated primary tumors in patients with gastric cancer. STUDY: Retrospective study of 2,668 patients with gastric cancer observed at our department between July 1974 and December 1999. Associated tumors were diagnosed using Warren and Gates criteria, and included tumors that were not considered to be a metastasis, invasion, or recurrence of gastric cancer. RESULTS: Of all, 3.4% (n = 78) had primary tumors other than gastric cancer, 27% of which were synchronous (n = 21) and 73%, metachronous (n = 57). The mean follow-up time was 4 years (range, 1-13 years), and the male-to-female ratio was 1:1. The median age at diagnosis of gastric cancer was 67 years (range, 37-84 years), 69 years for patients with synchronous tumors versus 60 years for those with metachronous (p = 0.050). For at least half the patients the median time interval to metachronous cancer was 3 years (range, 1-22 years). Seventy-eight percent (n = 61) had two cancers; most were colonic (19%), uterine and ovarian (16%), and breast tumors (13%). Seventeen percent (n = 13) had three tumors: colon (46%), breast (23%), and skin (23%). Four percent (n = 3) had four tumors. One case with seven tumors was also observed [colon, breast (two tumors), uterus, skin, and stomach (two tumors)]. No statistically significant differences were found between synchronous and metachronous with regard to sex, gastric cancer location, and staging (TNM). Sixty-three percent (n = 49) died while under observation. CONCLUSIONS: We found associated tumors in 3.4% of patients with gastric cancer. The most frequent associated tumors were breast and colon cancer. Surveillance for these tumors would be appropriate, at least in first years, after diagnosis of gastric cancer.     

Alterations of serum cholinesterase in patients with gastric cancer

AIM:To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance. METHODS:The velocity method was adopted to detect the activity of serum CHE in patients with gastric cancer and in patients with non-malignant tumor as controls. RESULTS:The serum CHE activity in the treatment group was significantly lower than that in the control group with a very significant difference between the two groups (83.3:113.1,P=0.0003). Age was significantly associated with the incidence of gastric caner. CONCLUSION:Serum CHE activity has a close relation with the incidence of gastric cancer.     

Postoperative chemotherapy in elderly patients with advanced gastric cancer

BACKGROUND/AIMS: The definitive efficacy of postoperative chemotherapy in elderly patients with advanced gastric cancer has not been established. The aim of this study is to evaluate prognosis in elderly patients with advanced gastric cancer and the effect of postoperative chemotherapy on prognosis. METHODOLOGY: Fifty-three patients, 75 years of age or older who underwent curative surgery for advanced gastric cancer were divided into 14 patients with postoperative chemotherapy (chemotherapy group) and 39 patients without postoperative chemotherapy (control group). Chemotherapy regimens were as follows: oral 5-FU alone (n = 11), intravenous mitomycin plus 5-FU: MF (n = 2), and MF plus oral 5-FU (n = 1). No prior chemotherapy or radiation was given. RESULTS: There were no significant differences of clinical and pathological backgrounds between the two groups. The rate of death due to recurrent carcinoma was 50.0% in the chemotherapy group and 43.6% in the control group, the difference being insignificant. Although the median survival time of the chemotherapy group (40.4 months) was longer than in the control group (31.7 months), a significant difference did not exist between the groups. The 1-, 3-, and 5-year survival rates did not significantly differ between the chemotherapy group versus the control group, 85.7% versus 82.1%, 42.9% versus 51.3%, and 35.7% versus 46.2%, respectively. CONCLUSIONS: Postoperative chemotherapy did not contribute to prolong survival in elderly patients with advanced gastric cancer mainly because the incidence of recurrent carcinoma was not reduced.     

Increased ischemia-modified albumin levels in patients with gastric cancer

Reactive oxygen species (ROS) are found in the development stages of carcinogenesis. Fifty two patients with gastric cancer and 35 controls were enrolled in this trial. IMA, MDA, Total Oxidant Status (TOS), Total Antioxidant Status (TAS) and Oxidative Stress Index (OSI) were evaluated. There was a significant increase in IMA and MDA levels in the patient group (0.405±0.111, 0.271±0.066; p= 0.0001 and 0.207±0.251, 0.077±0.103; p= 0.004 respectively). TOS was also higher in the patient group but it was not statistically different. TAS was statistically lower and there was significant difference in OSI (0.621±0.394, 0.996±0.37; p=0.0001 and 9.68±18.2, 2.9±3.85; p=0.001 respectively). The areas under receiver operating characteristics curves for the determination of gastric cancer were 0.842 for IMA and 0.708 for MDA. Increased levels of IMA, MDA and oxidative stress index were detected and this condition is associated with the impairment of oxidant-antioxidant balance.     

Pre- and postoperative electrogastrography in patients with gastric cancer

BACKGROUND/AIMS: To investigate the changes of electrogastrography (EGG) after stomach resection, fasting and postprandial EGG were recorded in 10 volunteers and 23 gastric cancer patients who had undergone total or subtotal gastrectomy. METHODOLOGY: EGG signals in patients were recorded before and after surgery and were analyzed by power spectrum. RESULTS: The power spectrum components at three cycles/minute (cpm) as normal subject, had completely disappeared in all patients after total gastrectomy, and irregular powers, especially under 9 cpm, had increased. These results suggest that the activity of the 3-cpm component is specific for the stomach. In subtotal gastrectomy patients, 3-cpm power peaks were clearly observed in seven of twelve patients, but it was not recorded in the remaining five patients, who showed irregular powers similar to that in patients after total gastrectomy. Therefore, it was speculated that the area containing the "pacemaker" of gastric electric potentials was removed during gastrectomy in these five patients. The postprandial dip, which is considered to reflect autonomic nervous function, was not observed in six of seven subtotal gastrectomy patients who demonstrated the 3-cpm component in their EGG, and it was speculated that the gastric branch of the vagus nerve in these six patients might have been partially removed by surgery. CONCLUSIONS: These findings suggest that EGG is available as a non-invasive method to evaluate the motility and autonomic function of the remnant stomach after gastrectomy.     

Elevated cyclooxygenase-2 expression in patients with early gastric cancer in the gastric pylorus

Background Duodenogastric reflux after surgery increases the risk of gastric carcinoma. To determine whether bile reflux influences the development of gastric cancer in patients who have not had surgery, we compared cyclooxygenase-2 (COX-2) immunoreactivity in early gastric cancer originating from the gastric pylorus and that originating from other locations. We also examined the effects of bile acids on the expression and activity of COX-2 in gastric cells in vitro.Methods Tumor sections from 79 patients who underwent endoscopic mucosal resection for early intestinal-type gastric carcinoma were stained using a COX-2-specific monoclonal antibody. Immunoblotting of COX-2 was used to assess the effects of bile acids on COX-2 expression and activity in human gastric cell lines.Results Among the 79 early gastric cancer lesions studied, 13 (16%) arose in the gastric pylorus. In this group, COX-2 immunoreactivity was negative to weak in 38% (5 of 13 lesions) and moderate to strong in 62% (8 of 13 lesions). In the control group, COX-2 immunoreactivity was negative to weak in 70% (46 of 66 lesions) and moderate to strong in 30% (20 of 66 lesions). COX-2 expression was significantly elevated in early gastric cancer located in the gastric pylorus, compared with that in the other locations. In human gastric cell lines, bile acids induced COX-2 expression, mediated by the ERK 1/2 mitogen-activated protein kinase pathway.Conclusions COX-2 expression is elevated in early gastric cancer of the gastric pylorus, a common site of gastric cancer. Bile acids induced COX-2 expression in human gastric cell lines, suggesting a role of bile reflux in gastric carcinogenesis.     

残胃癌患者的生命质量评价

目的 研究残胃癌患者的健康相关生命质量(HRQoL)及其影响因素.方法 选取因早期胃癌接受胃大部切除术≥10年者130例,根据术后残胃是否发生癌变分为残胃癌组80例和残胃组50例.2组均接受癌症普适性量表生命质量测定量表(QLQ)-C30和胃癌特异性量表QLQ-STO22调查,评价其HRQoL.正态分布数据两组间比较行t检验.非正态分布数据两组间比较行Wilcoxon秩和检验.采用最优尺度回归分析筛选HRQoL相关的临床影响因素.结果 所有研究对象均完成量表调查.与健康对照组比较,残胃癌组总体生命质量评价、躯体功能、角色功能、情绪功能、认知功能、社会功能评分皆较低,差异均有统计学意义(t=-6.678、-7.111、-10.605、-5.748、-4.765、-21.170,P均＜0.01),疲倦、疼痛、腹泻、恶心与呕吐、食欲不振、经济困难、吞咽困难、腹痛、反流症状、饮食受限、焦虑、身体外观、脱发评分皆较高,差异均有统计学意义(t=6.925、4.218、4.728,Z=-5.236、-7.890、-7.698、-10.058、-3.612、-6.914、-9.711、9.940、-7.987、-4.966,P均＜0.01).与残胃组比较,残胃癌组总体生命质量评价、躯体功能、角色功能、情绪功能、认知功能、社会功能评分皆较低,差异均有统计学意义(t=-5.861、-5.821、-7.077、-7.999、-2.808、-5.710,P均＜0.01),疲倦、疼痛、恶心与呕吐、食欲不振、经济困难、吞咽困难、饮食受限、焦虑、身体外观、脱发评分皆较高,差异均有统计学意义(t=9.363、6.842,Z=-2.654、-6.256、-3.266、-4.132、-2.854、-7.996、-4.258、-2.005,P均＜0.01).与健康对照组比较,残胃组社会功能评分较低,差异有统计学意义(t=-9.820,P＜0.01),腹泻、恶心与呕吐、经济困难、吞咽困难、反流症状、饮食受限、身体外观、脱发评分皆较高,差异均有统计学意义(t=3.020,Z=-1.981、-3.775、-6.505、-6.098、-8.032、-3.369、-3.147,P均＜0.05),疲倦和疼痛的症状评分则较低,差异均有统计学意义(t=-2.890、-2.439,P均＜0.05).患者的HRQoL与学历、婚姻状况、家庭收入、残胃病程均正相关.结论 残胃癌患者的HRQoL均有不同程度下降.学历、家庭收入、残胃病程、婚姻状况等因素会影响残胃癌患者的HRQoL.     

Neutrophil functions and cytokine production in patients with gastric cancer

BACKGROUND/AIMS: One of the most important factors in the prevention of postoperative infection is the patient's own capacity to protect against infection. Neutrophils play a major role in this protection through phagocytosis and superoxide generation. Inflammatory cytokines are suitable for estimating the degree of surgical stress. The present study was designed to elucidate whether neutrophil functions are impaired in gastric cancer patients, and are related with cytokine production after surgery. METHODOLOGY: Phagocytosis and superoxide generation by neutrophils was studied in 84 patients with gastric cancer by flow cytometry. IL-6, IL-8 and tumor necrosis factor alpha were studied in 18 patients with gastric cancer by enzyme-linked immunosolubent assay. RESULTS: In gastric cancer patients phagocytosis was not impaired, whereas superoxide generation was lower than benign diseases and it was inhibited relative to the clinical stage. Moreover, superoxide generation was correlated with the nutritional parameters and was more suppressed in 7 patients who suffered from postoperative infection than in 40 patients whose postoperative course were uneventful. The fluctuation of superoxide generation correlated well with the serum cytokine levels in the postoperative course and its correlation was clarified in vitro. Nine patients with gastric cancer received intravenous hyperalimentation, and their superoxide generation was increased. CONCLUSIONS: Superoxide generation by neutrophils was suppressed in gastric cancer patients and it is suggested that nutritional support prevents postoperative infection via the augmentation of superoxide generation.     

Time-dependent relevance of prognostic factors in patients with gastric cancer

BACKGROUND/AIMS: Prognostic factors are useful for establishing a prognosis of patients from the time of operation. However, the value of individual prognostic factors may change dependent on the length of the follow-up period, and it is not clear how long these factors keep their prognostic relevance. METHODOLOGY: Data was used from 233 Japanese patients treated by potentially curative resection for primary gastric cancer, between 1993 and 1998. Survival analysis was done starting at 1-yearly intervals after operation and follow-up in the first analysis started at the time of the operation. RESULTS: Prognostic relevance of tumor size was not evident for total follow-up time but was significantly emphasized 1 year after operation. Serosal invasion lost its prognostic value within one year of operation. The status of lymph node metastases retained its ability to predict survival after 2 years' follow-up whereas after 3 years' follow-up nodal status seemed to be without significance. CONCLUSIONS: A distinct time-dependency with varied patterns was found in the influence of some prognostic factors on survival. Detecting the changing importance of prognostic factors could provide new biological insights that might otherwise be missed, and may help determine the most appropriate clinical use of various factors.     

Prognostic factors and survival in patients with gastric stump cancer

AIM:To elucidate the clinicopathological characteristics and prognostic factors of gastric stump cancer(GSC).METHODS:The clinical data for 92 patients with GSC were collected at Fudan University Shanghai Cancer Center.The prognostic factors were analyzed with Cox proportional hazard models.RESULTS:GSC tended to occur within 25 years following the primary surgery,when the initial disease is benign,whereas it primarily occurred within the first15 years post-operation for gastric cancer.Patients with regular follow-up after primary surgery had a better survival rate.The multivariate Cox regression analysis revealed that Borrmann type?Ⅰ/Ⅱ(HR=3.165,95%CI:1.055-9.500,P=0.040)and radical resection(HR=1.780,95%CI:1.061-2.987,P=0.029)were independent prognostic factors for GSC.The overall 1-,3-,and 5-year survival rates of the 92 patients were78.3%,45.6%and 27.6%,respectively.The 1-,3-,and 5-year survival rates of those undergoing radical resection were 79.3%,52.2%,and 37.8%,respectively.The 5-year survival rates for stages?Ⅰ,Ⅱ,Ⅲ,andⅣwere 85.7%,47.4%,16.0%,and 13.3%,respectively(P=0.005).CONCLUSION:The appearance of GSC occurs sooner in patients with primary malignant cancer than in patients with a primary benign disease.Therefore,close follow-up is necessary.The overall survival of patients with GSC is poor,and curative resection can improve their prognosis.     

The role of surgery in patients with advanced gastric cancer

Surgery remains the mainstay of treatment with curative intent for established gastric cancer. Patient selection is critical to achieving satisfactory outcomes, and involves careful assessment of both patient fitness and disease stage. Staging techniques have multiplied and become much more sensitive in recent years. Current best practice involves a combination of spiral CT scan, Endoscopic ultrasound, PET scanning and laparoscopy. Only a minority of patients progress to potentially curative surgery after staging and fitness assessment in Western centres. Conventional treatment involves a distal subtotal gastrectomy or total gastrectomy depending on the site of the lesion. Innovative techniques include the Merendino operation, and pylorus and nerve sparing gastrectomies for earlier stage disease in the proximal and distal stomach, respectively. There is evidence of nutritional and quality of life benefit in the first 2 years after surgery from formation of a gastric substitute reservoir. Laparoscopic resection is well established in Japan and is developing rapidly elsewhere but its role and outcomes are not yet well defined. Radical lymph node dissection remains controversial: randomised trial evidence of overall benefit is lacking, but expert series have produced excellent results, and there are indications of a sub-group benefit for patients with stage II and III disease. The increased morbidity and mortality associated with radical dissection appear to be largely attributable to pancreatic and splenic resection together with limitations in Unit expertise. Surgical palliation has become less important in recent years as interventional radiology and endoscopy techniques have been developed for the same purposes. Overall mortality and survival results have improved dramatically over the last 20 years, but interpretation of these figures is made difficult by major changes in staging and case selection. The chances of long-term survival are, however, clearly much greater, and those of peri-operative death much less for an individual patient accepted for surgery in 2006 than they would have been in 1986.