Defective autologous mixed lymphocyte reaction (AMLR) in gastric cancer patients

Autologous mixed lymphocyte reaction (AMLR) is an important reaction regulating the immune system in the various diseases. This is the first report investigating AMLR not only in peripheral blood but also in the spleen of gastric cancer patients. AMLR in the spleen of gastric cancer patients was significantly suppressed compared with that of peripheral blood of gastric cancer patients and patients without cancer. In investigation of AMLR composed of peripheral blood cells and spleen cells of gastric cancer patient, AMLR on splenic non-T cells as a stimulator was significantly suppressed compared with peripheral blood non-T cells as a stimulator. It suggests that abnormalities of non-T cells caused suppression of AMLR in the spleen of gastric cancer patients.     

Autologous mixed lymphocyte-tumor reaction and autologous mixed lymphocyte reaction. I. Proliferation of two distinct T-cell subsets

In patients with carcinomatous pleural effusions blood T lymphocytes proliferated in vitro in response to autologous, freshly isolated effusion tumor cells in the autologous mixed lymphocyte-tumor culture (AMLTC) and to autologous blood non-T cells in the autologous mixed lymphocyte culture (AMLC). Treatment of the stimulator cells with the anti-HLA-DR monoclonal antibody (MAb) abrogated the stimulatory capacity in AMLC, but not in AMLTC. A subset of T cells that formed rosettes with autologous erythrocytes showed proliferative response to autologous non-malignant cells, whereas this subset did not respond to autologous tumor cells. Non-adherent lymphocytes were fractionated by centrifugation on discontinuous Percoll density gradients. Medium-sized T lymphocytes were excellent responders in AMLC, but were weak responders in AMLTC. Small T lymphocytes proliferated preferentially in AMLTC, but responded poorly in AMLC. Large granular lymphocytes (LGL) did not proliferate in mixed cultures of either type. Instead, LGL suppressed the T-cell proliferation in AMLTC. The same suppressor LGL, however, had no inhibitory effect on AMLC. Elimination of the CD4 subset reduced or abolished proliferative response in AMLC in all cases, whereas it was ineffective in diminishing the reaction in 6 of 8 AMLTC. In contrast, removal of the CD8 subset decreased or eliminated T-cell proliferation in 4 of 8 AMLTC, but in none of the AMLC. These results indicate that the autoreactive T lymphocytes detectable in response to tumor cells and non-malignant non-T cells differ in several characteristics. Thus, the reaction in the AMLTC is not due to contaminating non-malignant cells in the stimulator population and may be a tumor-induced proliferative response.     

Langerhans cells and prognosis in patients with gastric carcinoma

Infiltration of Langerhans cells (LC) and macrophages into tumor tissues was investigated using immunohistochemical methods, anti-S-100 protein and anti-lysozyme antibodies in 174 cases of gastric carcinoma. Varying population densities of S-100-positive LC were noted in tumor tissues; lysozyme-positive macrophages, however, were found in almost equal quantities. LC were mainly interspersed among the tumor cells, whereas macrophages were present in the stroma and around the necrotic foci. Although the survival time of patients with Stage I, II or IV gastric carcinoma did not relate to the density of LC, survival time in Stage III patients correlated well with the density of LC. In patients with a marked infiltration of LC, survival time was longer than in cases of only a slight infiltration (P less than 0.001). Therefore, LC in immunological defense mechanisms of the host against the tumor may be clinically effective in a certain phase of tumor development.     

Autologous mixed lymphocyte-tumor reaction and autologous mixed lymphocyte reaction. II. Generation of specific and non-specific killer T cells capable of lysing autologous tumor

The specific and non-specific nature of autotumor cytotoxicity induced in autologous mixed lymphocyte-tumor culture (AMLTC) and autologous mixed lymphocyte culture (AMLC) was studied in patients with carcinomatous pleural effusions. Small- and medium-sized blood lymphocytes that were isolated by centrifugation on discontinuous Percoll gradients did not lyse autologous, freshly isolated effusion tumor cells. In vitro activation of the small lymphocytes, but not of the medium lymphocytes, with autologous tumor cells generated cytotoxic potential restricted to autologous tumor. When stimulated with autologous non-malignant non-T cells, the medium lymphocytes, but not small lymphocytes, were triggered to cytotoxicity that acted not only on autologous tumor cells but also on allogeneic tumor cells, T blasts, and tumor cell lines. Experiments using monoclonal antibodies (MAb) and complement (C') showed that both types of killer cells were CD2+ CD3+ CD16- T cells. Autotumor cytotoxicity developed in AMLTC was mediated by the CD4- CD8+ T cell subset in 6 of 9 cases and the CD4+ CD8- subset in the other 3 cases. In contrast, cytotoxicity induced in AMLC was exerted exclusively by the CD8+ subset. The enrichment of blasts from cultured T cells on discontinuous density gradients enhanced autotumor killing activity, with no reactivity recorded for blast-depleted, resting T cells. Addition of mitomycin-C-treated large granular lymphocytes (LGL) to AMLTC abolished the induction of autotumor killer cells, whereas non-specific killer cells were generated in AMLC irrespective of the presence of LGL. These results indicate that stimulation of autoreactive T cells in AMLTC and in AMLC could induce 2 distinct types of autotumor killer cells.     

Relationship between area of serosal invasion and prognosis in patients with gastric carcinoma

We examined the relationship between the spatial extent of invasion of the gastric serosa in patients with gastric carcinoma and their postoperative 5-year survival rate. At the time of surgical resection of gastric cancer, intraperitoneal free cancer cells were detected by lavage of the Douglas cavity in 135 of 309 (44%) patients with gross evidence of serosal invasion. Examination of the relationship between the presence of intraperitoneal free cancer cells and serosal area invaded by the tumor revealed that only 22% of cases with an area of serosal invasion 10 cm2 or less were positive for free cancer cells, but such cells were found in 72% of cases with an area of serosal invasion greater than 20 cm2. The 5-year survival rate was 31% in patients with an area of serosal invasion of less than 10 cm2, whereas the rate was only 8% in patients with an area of serosal invasion greater than 20 cm2. Not only the presence of serosal invasion by a tumor but also the spatial extent of the invasion are significant factors that influence the prognosis of patients with gastric carcinoma.     

65例可切除老年胃癌临床病理特征和预后分析

目的:分析65例可切除老年胃癌患者的临床病理特征和预后。方法:回顾性分析病理证实的65例年龄≥65岁老年可切除胃癌患者的临床病理特征和预后。60例(92.3%)患者行R0切除。62例(95.4%)患者行D2术。18例(27.7%)患者行术后辅助化疗。Kaplan-Meier法分析生存率,Log-rank检验比较组间生存差异。结果:65例患者中,男49例,女16例。60例(92.3%)患者为腺癌。TNM分期为I-II和III期患者分别为15例(23.1%)和50例(76.9%)。32例(49.2%)患者伴有合并症,6例(9.2%)伴有1个以上合并症。全组患者2年总生存率(overall survival,OS)、无进展生存率(progression-free survival,PFS)和癌症特异生存率(cancer-specific survival,CSS)分别为42.6%、28.4%和49.0%。单因素分析发现,N0-1患者的预后明显优于N2-3的患者,2年OS、PFS和CSS分别为77.9%和31.6%(P=0.010)、78.6%和16.3%(P=0.002)以及83.1%和37.3%(P=0.023)。死亡原因分析发现,33例死亡患者中,肿瘤相关死亡25例(75.8%),治疗相关或合并症相关死亡8例(24.2%)。结论:可切除老年胃癌的合并症多见,治疗相关或合并症相关死亡多见,N分期是最重要的临床预后因素。     

Preoperative cell-mediated immune function and the prognosis of patients with gastric carcinoma

The cell-mediated immune function of 83 patients with gastric carcinoma was assessed preoperatively and the results were compared to that of 52 patients with benign lesions. The data were subjected to an analysis in order to evaluate their prognostic significance. The abilities to induce allogeneic cytotoxicity and to produce interleukin 2 (IL 2) in patients with stage IV carcinoma were significantly depressed, as compared to those in patients with benign lesions, whereas natural killer (NK) cell activity was not significantly impaired. There was no significant correlation among these immune functions. When the patients were stratified into two groups, those who had high (greater than the mean value in patients with benign lesions) and low (less than the same value) values of these immune reactivities, the survival of patients with high NK activity (?43%) was significantly better, as compared to that of patients with low cytotoxicity (< 43%). However, there was no correlation between the survival and allogeneic cytotoxicity in these patients. The high ability to produce IL 2 (?1.3 U/ml) correlated with the better survival in the patients, but not in the group of patients who underwent curative resection.     

Relationship between Langerhans cells and prognosis of patients with gastric carcinoma]

Langerhans cells (LCs) in 73 cases of gastric carcinomas (GC) were quantitatively investigated by ABC immunohistochemical method using anti-S-100 protein antibody. The mean density of LCs (cell numbers/mm2) infiltrating the carcinomas showed an intimate relationship with the prognosis (P < 0.01) and the status of lymph node (LN) metastasis (P < 0.05). The density of LCs in patients without LN metastasis was significantly higher than that with LN metastasis. In 73 cases of GC, there were 35 cases of LCs(+) and 38 of LCs(++) groups. The mean survival times were 29.81 months in the former and 52.21 months in the latter. A significant relationship (P < 0.05) between the survival and degree of the density of LCs was showed by Student's t test and life table method. There were no correlation among the density of LCs and gross appearance, depth of invasion, histologic type and patients' sex. The fact indicated that LCs may play an important role in immunological defense mechanisms of host against the tumor. Patients with dense infiltration of LCs survived longer and showed less LN metastasis than those without such an infiltration. It is considered that measurement of LCs in specimens of GC may be taken as one of criteria of prognosis.     

胃癌患者术前贫血与术后并发症及预后的相关性

目的:探讨术前贫血和贫血程度与胃癌并发症及预后的关系.方法:对2008年10月至2016年11月期间空军军医大学西京医院消化外科3692例行胃癌根治术患者的临床资料进行分析.探索术前贫血和贫血程度对胃癌术后并发症和预后的影响.结果:3692例患者中,男性2889例(78.3％),女性803例(21.7％).贫血患者14...     

早期舌鳞状细胞癌患者术后预后的影响因素分析

目的 探讨早期舌鳞状细胞癌患者术后预后的影响因素.方法 收集90例接受手术治疗的早期舌鳞状细胞癌患者的病历资料,所有患者术后随访3年,统计患者的生存情况.采用Cox比例风险回归模型分析早期舌鳞状细胞癌患者预后的影响因素.结果 90例早期舌鳞状细胞癌患者随访3年未出现失访病例,病死率为27.78％(25/90),3年生存率为72.22％(65/90).不同性别、吸烟情况、饮酒情况、肿瘤部位、肿瘤类型、临床T分期、颈部淋巴结清扫情况、术后化疗情况的早期舌鳞状细胞癌患者的3年生存率比较,差异均无统计学意义(P﹥0.05);不同年龄、组织分化程度、肿瘤复发情况、颈部淋巴结转移情况、术后放疗情况的早期舌鳞状细胞癌患者的3年生存率比较,差异均有统计学意义(P﹤0.05).Cox多因素回归分析结果显示,年龄≥60岁、低分化、肿瘤复发、颈部淋巴结转移及术后未放疗均是早期舌鳞状细胞癌患者预后的独立危险因素(P﹤0.05).结论 早期舌鳞状细胞癌患者术后预后的影响因素较多,临床可根据具体影响因素进行针对性改善,重视术后复发、转移监测和辅助治疗,降低患者术后复发、转移风险,进而改善其预后.     

术后PNI在胃癌患者预后评估中的临床价值

目的 探讨术后PNI在胃癌患者预后评估中的临床价值。方法 回顾性分析术后胃癌Ⅲ期患者91例,根据术后、首次化疗前的外周血液指标计算出PNI、外周血中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）、全身炎症指数（SII）等营养综合指标,通过ROC曲线计算出PNI最佳截断值。根据PNI最佳截断值将其分为低PNI组（PNI<42.3）和高PNI组（PNI≥42.3）,根据PNI分组预测胃癌患者的预后。应用Cox回归模型进行单因素回归分析和多因素分析。结果 多因素分析结果显示术后PNI（P=0.004）及分期（P=0.009）是影响胃癌患者总生存时间的独立预后因素。结论 术后PNI是预测胃癌患者预后的独立因素,且低PNI和高分期与患者预后不良相关。     

胃癌合并腹水患者预后因素的Cox回归分析

目的 探讨影响胃癌合并腹水患者生存的预后因素。方法 回顾性分析2011年10月至2013年10月于本院住院治疗且随访资料完整的58例晚期胃癌合并腹水患者的病例资料,采用Kaplan-Meier法进行生存分析,Log-rank法进行单因素分析,Cox比例风险模型进行多因素分析。结果 58例胃癌合并腹水患者的中位生存期为14.0月。单因素分析显示分化程度、浸润深度、肝脏转移情况、KPS评分和治疗方法 与患者预后有关,而性别、年龄和腹水量则与预后无关。经Cox多因素回归分析,分化程度、浸润深度、肝脏转移情况、KPS评分及治疗方法 是影响胃癌合并腹水患者预后的独立危险因素。结论 分化程度、浸润深度、肝脏转移情况、KPS评分及治疗方法 是影响胃癌合并腹水患者预后的强相关因素,可作为独立预后指标指导胃癌合并腹水患者的治疗。     

Putative risk factors for postoperative pneumonia which affects poor prognosis in patients with gastric cancer

Background and objectives

Several recent studies identified that postoperative infectious complications contribute to recurrence and poor outcome in patients with gastric cancer. This study was designed to investigate the prognostic impact of postoperative pneumonia, and to identify the putative risk factors for its occurrence.

Methods

We retrospectively analyzed 1,415 consecutive patients who underwent curative gastrectomy for gastric cancer between 1997 and 2013.

Results

A total of 31 (2.2 %) patients developed postoperative pneumonia (Clavien–Dindo classification ≥II). Patients with postoperative pneumonia showed a significantly poorer prognosis than patients without (P < 0.001). Concerning the occurrence of postoperative pneumonia, univariate and multivariate analyses identified older age (≥65 years; P = 0.010; odds ratio [OR] 3.59), lower nutritious status (albumin <3 0; P = 0.029; OR 4.51), advanced stage (pStage ≥II; P = 0.045; OR 2.35), concurrent hypertension (P = 0.042; OR 2.21) and total gastrectomy (P = 0.026; OR 2.42) as independent risk factors.

Conclusions

Postoperative pneumonia was shown to be associated with long-term poor outcome in patients with gastric cancer. Care should be taken for patients with clinical factors such as older age, lower nutritional status, advanced stage, concurrent hypertension, and total gastrectomy.

     

Systemic inflammation score predicts postoperative prognosis of patients with clear-cell renal cell carcinoma

Background:

Growing evidence indicates that inflammation has a crucial role in the development and progression of cancer. We developed a novel systemic inflammation score (SIS) based on preoperative serum albumin and lymphocyte-to-monocyte ratio (LMR), and examined its prognostic value for patients with clear-cell renal cell carcinoma (ccRCC) after surgery.

Methods:

The study comprised 441 ccRCC patients undergoing nephrectomy between 2008 and 2009 in a single centre. The SIS was developed and its associations with clinicopathological features and overall survival (OS) were evaluated.

Results:

The SIS consisted of serum albumin and LMR that were both retained as independent indicators adjusting for other haematological and laboratory markers of systemic inflammation responses and traditional clinicopathological features. A high SIS was significantly associated with aggressive tumour behaviours and served as an independent prognostic factor of reduced OS. Furthermore, the SIS could significantly stratify patient prognosis in different tumour stages and Mayo Clinic stage, size, grade and necrosis scores. Incorporation of the SIS into a prognostic model including TNM stage, Fuhrman grade and lymphovascular invasion generated a nomogram, which predicted accurately 3- and 5-year survival for ccRCC patients.

Conclusions:

The SIS as a potentially powerful prognostic biomarker might improve traditional clinicopathological analysis to refine clinical outcome prediction for ccRCC patients after surgery.     

Association of depressed mixed lymphocyte reactivity with the development of bladder carcinoma in patients with papillomas

Patients with bladder papillomas have an excellent overall prognosis, although approximately 10% of such patients develop frank bladder cancer. It is therefore important to devise methods for subclassifying bladder papillomas in an attempt to identify those patients at high risk for progression to carcinoma. The lymphoproliferative responses in 27 patients with bladder papillomas were tested in the mixed lymphocyte reaction (MLR). Patient responses were compared to those of normal individuals tested simultaneously. A relative proliferation index (RPI) was defined as a percent response relative to the mean normal response. A RPI less than 0.5 was defined as a depressed MLR and greater than 0.5 as a normal MLR. All patients were followed at three-month intervals for at least five years for the development of superficial or invasive bladder carcinoma. Of the 27 patients, 12 had a depressed MLR and 10/12 (83%) developed cancer within five years. Of the 15 patients with a normal MLR, only three developed bladder carcinoma. The number of papilloma patients surviving free of bladder carcinoma at five years was 12/15 (80%) with a normal MLR and 2/12 (17%) with a depressed MLR (P less than 0.01). Measurement of the MLR appeared to offer a useful adjunct in the evaluation of staging and biologic potential of bladder papilloma.     

Podoplanin associates with adverse postoperative prognosis of patients with clear cell renal cell carcinoma

Podoplanin, a transmembrane sialomucin‐like glycoprotein, was recently shown to be involved in tumor progression and metastasis, and its potential role in facilitating platelet‐based tumor embolization and promigratory phenotype of cancer cells was also demonstrated. In this study, we assessed the clinical significance of tumoral podoplanin expression in 295 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays and analyzing the staining intensity. Univariate analysis suggested an adverse prognostic effect of high tumoral podoplanin expression on patients' overall survival (OS) and recurrence‐free survival (RFS) (P < 0.001 for both). In the multivariate analysis, high tumoral podoplanin expression (using staining intensity as either a continuous or dichotomous variable) was still an independent adverse prognostic factor for patient survival (OS, P < 0.001, RFS, P < 0.001 for continuous; OS, P < 0.001, RFS, P = 0.002 for dichotomous). Moreover, stratified analysis identified a higher prognostic power in the intermediate/high risk patient groups. After utilizing those parameters in the validated multivariate analysis, two nomograms were constructed to predict ccRCC patients' OS and RFS (c‐index 0.815 and 0.805, respectively), and performed better than existing integrated models (P < 0.001 for all comparisons). In conclusion, high tumoral podoplanin expression could independently predict an adverse clinical outcome for ccRCC patients, and it might be useful in future for clinical decision‐making and therapeutic developments.     

胃癌患者手术前后NK及T细胞的改变

目的：评价胃癌患者手术前、后ＮＫ及Ｔ细胞动态变化。方法：采作单克隆抗体方法及ＭＴＴ法检测Ｔ３６例胃癌患者手术前、后Ｔ淋巴细胞亚群（ＴＣ）及自然杀伤细胞（ＮＫ）活性,并与３０例正常对照进行了比较,结果：术前患者ＣＤ３（＋）、ＣＤ４（＋）、ＣＤ４（＋）／ＣＤ８（＋）比值、ＮＫ细胞活性显著降低（Ｐ〈０．０１。ＣＤ８（＋）细胞增高（Ｐ〈０．０１）。术后２０天,患者细胞免疫功能逐渐恢复。与术前比较除ＣＤ４（＋）外,其余均有显著性意义（Ｐ〈０．０５）。结论：胃癌患者细胞免疫功能与肿瘤的消长有密切关系。ＴＣ亚群和ＮＫ细胞活性可作为判定疗效和预后的一个重要监测指标。     

胃癌淋巴结转移枚数与手术后放射治疗效果的相关性

目的探讨分析胃癌淋巴结转移枚数与术后放疗疗效及相应病理检查结果的相关性。方法 2006年5月至2008年5月收治的胃癌患者,均行胃癌根治性手术治疗,术后诊断为胃癌伴淋巴结转移的患者214例。所有组内淋巴结转移行D2或D3式清扫,且治疗前后均予以放射治疗。结果胃癌患者淋巴结转移枚数与性别、年龄等一般因素无关系,而与肿瘤大小、浸润深度及分期呈正相关。淋巴结转移1⁵个、65个、6⁹个及>9个的胃癌患者,其术后及放疗后5年生存率分别为50%、30%和<10%,三者之间差异有统计学意义(P<0.05)。结论胃癌患者胃周阳性淋巴结转移数与预后有关,结合肿瘤大小及生长浸润方式可以简便而准确地判断胃癌术后患者的预后情况。     

中性粒细胞/淋巴细胞比值血小板/淋巴细胞比值与TACE治疗肝癌患者预后的相关性

  目的  本研究探讨中性粒细胞与淋巴细胞比值（neutrophil to lymphocyte ratio,NLR）和血小板与淋巴细胞比值（platelet to lymphocyte ratio,PLR）与接受肝动脉栓塞化疗（transarterial chemoembolization,TACE）肝癌（hepatocellular carcinoma,HCC）患者术后生存期的相关性。  方法  回顾性分析2007年1月至2015年6月中山大学肿瘤防治中心肝胆胰科确诊为肝癌并行TACE治疗的216例患者。研究患者依照NLR和PLR的界值分成两组。分析并比较NLR和PLR在不同随访时间点的受试者工作曲线（ROC）下面积。单因素和多因素分析用于评价NLR和PLR与TACE术后肝癌患者预后的相关性。  结果  本研究中位随访时间为431.1 d。全体研究对象1、2、3年生存率分别为61.3%、44.2%和40.5%。中位生存时间为410.5 d。术前NLR＜1.77组和术前NLR≥1.77组1、2、3年生存率分别为81.6%、63.0%、45.7%和43.1%、27.0%、19.3%,差异具有统计学意义（P < 0.001）。术前PLR < 94.62组和术前PLR≥94.62组1、2、3年生存率分别为62.7%、47.0%、37.0%和46.8%、29.0%、18.5%,差异具有统计学意义（P=0.002）。多因素分析显示NLR≥1.77与TACE术后肝癌患者较差预后相关,是肝癌患者TACE治疗后的危险因素。  结论  TACE介入术前HCC患者的NLR水平,作为系统炎症的一个反应指标,是影响其预后的危险因素。