Spontaneous and lymphokine-induced cytotoxic activity of monkey intestinal mucosal lymphocytes

We determined the capacity of primate (macaque monkey) intestinal mucosal lymphocytes to mediate natural killer cytotoxicity, and characterized the nature of cells mediating this form of cytotoxicity in the intestine. Isolated macaque monkey intestinal mucosal lymphocytes were found to have intermediate levels of spontaneous cytotoxicity against K562 target cells compared to higher values found in lymphocytes of peripheral blood (PBL) and spleen and low values for mesenteric lymph node (MLN) lymphocytes. Intestinal lymphocytes were similar to PBL in having the same range of target cell specificites, in having augmentation of activity by interferon or interleukin 2, and in demonstrating specificity in cold target inhibition studies. Both intestinal and PBL spontaneous cytotoxic function in primates was mediated predominantly by cells bearing antigens cross-reactive with the anti-human monoclonal antibody Leu-11. The percentage of Leu-11+ lymphocytes was significantly lower in isolated intestinal, spleen, and MLN lymphocytes compared to peripheral blood. Furthermore, isolated intestinal lymphocytes differed from PBL in that intestinal Leu-11+ were predominantly Leu-15-, while Leu-11+ PBL were predominantly Leu-15+. These studies demonstrate that the lower spontaneous cytotoxic function of intestinal mucosal lymphocytes compared to PBL is associated with a lower number of effector cells and with effector cells which differ qualitatively in expression of the Leu-15 antigen.     

Significance of Lymph Node Metastasis in Cancer Dissemination of Head and Neck Cancer

Lymph node metastasis (LNM) in many solid cancers is a well-known prognostic factor; however, it has been debated whether regional LNM simply reflects tumor aggressiveness or is a source for further tumor dissemination. Similarly, the metastatic process in head and neck cancer (HNC) has not been fully evaluated. Thus, we aimed to investigate the relative significance of LNM in metastatic cascade of HNC using functional imaging of HNC patients and molecular imaging in in vivo models. First, we analyzed ¹⁸Fluorodeoxyglucose positron emission tomography (PET) parameters of 117 patients with oral cancer. The primary tumor and nodal PET parameters were measured separately, and survival analyses were conducted on the basis of clinical and PET variables to identify significant prognostic factors. In multivariate analyses, we found that only the metastatic node PET values were significant. Next, we compared the relative frequency of lung metastasis in primary ear tumors versus lymph node (LN) tumors, and we tested the rate of lung metastasis in another animal model, in which each animal had both primary and LN tumors that were expressing different colors. As a result, LN tumors showed higher frequencies of lung metastasis compared to orthotopic primary tumors. In color-matched comparisons, the relative contribution to lung metastasis was higher in LN tumors than in primary tumors, although both primary and LN tumors caused lung metastases. In summary, tumors growing in the LN microenvironment spread to systemic sites more commonly than primary tumors in HNC, suggesting that the adequate management of LNM can reduce further systemic metastasis.     

Tumor infiltration by adoptively transferred T cells is independent of immunologic specificity but requires down-regulation of L-selectin expression.

Adoptive immunotherapy with anti-CD3/IL-2 activated tumor-draining lymph node (LN) T cells is capable of eradicating tumor established at various histological sites. Tumor-specific effector lymphocytes have recently been identified to be LN T cells with down-regulated L-selectin (L-selectin-). Using fluorochrome labeling, the present study determined the early trafficking pattern of systemically transferred cells. In mice with 10-day established pulmonary 3-methylcholanthrene (MCA) 205 metastases, accumulation of cells in tumors was evident as early as 2 h after i.v. cell transfer, and, by 24 h, >50-fold higher numbers of cells were seen in metastases than in normal tissues. Similarly, transferred cells selectively infiltrated s.c. tumors, albeit at a lower rate. Analysis of the transferred cells isolated from recipient mice revealed that tumor-infiltrating cells were mostly L-selectin- (>95%). By contrast, only 24% and 58% L-selectin- cells were found in the LN and spleen, respectively. The ability of L-selectin- cells to accumulate at tumor sites was confirmed by the transfer of purified cell populations. Despite this selective tumor infiltration, the trafficking pattern did not reflect antigenetic specificity, and tumor regression occurred only after the transfer of tumor-specific effector cells. These results, thus, suggest that there are two distinct mechanisms operative in successful adoptive immunotherapy. Early infiltration of tumors by transferred cells is dictated by the physiological properties of cells and is independent on their immunologic specificity. Tumor regression, however, requires immunologically specific interactions at the site of tumor.     

Tumor Infiltrating PD1-Positive Lymphocytes and the Expression of PD-L1 Predict Poor Prognosis of Soft Tissue Sarcomas

Recently, the possibility of PD1 pathway-targeted therapy has been extensively studied in various human malignant tumors. However, no previous study has investigated their potential application for soft-tissue sarcomas (STS). In this study, we evaluated the clinical impact of intra-tumoral infiltration of PD1-positive lymphocytes and PD-L1 expression in tumor cells in 105 cases of STS. Intra-tumoral infiltration of PD1-positive lymphocytes and PD-L1 expression were seen in 65% and 58% of STS, respectively. Both PD1-positivity and PD-L1 expression were significantly associated with advanced clinicopathological parameters such as higher clinical stage, presence of distant metastasis, higher histological grade, poor differentiation of tumor, and tumor necrosis. Moreover, both PD1-positivity and PD-L1 positivity were independent prognostic indicators of overall survival (OS) and event-free survival (EFS) of STS by multivariate analysis. In addition, the combined pattern of PD1- and PD-L1-positivity was also an independent prognostic indicator for OS and EFS by multivariate analysis. The patents with a PD1⁺/PD-L1⁺ pattern had the shortest survival time. In conclusion, this study is the first to demonstrate that the infiltration of PD1 positive lymphocytes and PD-L1 expression in STS cells could be used as novel prognostic indicators for STS. Moreover, the evaluation of PD1- and PD-L1-positivity in STS is also available as possible criteria for selection of patients suitable for PD1-based immunotherapy.     

Patterns of initial recurrence and prognosis after sentinel lymph node biopsy and selective lymphadenectomy for melanoma

The histologic status of the sentinel lymph node is a highly significant prognostic factor for patients with clinically localized cutaneous melanoma. The patterns of initial treatment failure of patients with positive sentinel lymph node biopsy versus those with negative results have not been well described. The purpose of this study was to determine the relative prognostic importance of sentinel lymph node status and to compare patterns of initial treatment failure and prognosis of node-positive versus node-negative cutaneous melanoma patients staged by sentinel lymph node biopsy and selective lymphadenectomy. The authors reviewed the pertinent demographic and surgical data in a consecutive series of patients with cutaneous melanoma who underwent sentinel lymph node staging of nonpalpable regional nodes. Sentinel lymph node biopsy was performed using a combination of blue dye and radiolocalization. Patients with positive biopsy results underwent selective lymphadenectomy, whereas those with negative results were observed. Site(s) and date(s) of initial recurrence and death were determined, and disease-free and overall survival probabilities were compared between positive and negative groups using the log-rank test and multivariable Cox regression analysis. Between February of 1994 and August of 2000, 408 patients with melanoma underwent sentinel lymph node biopsy to stage 518 regional lymph node basins. Mean Breslow tumor thickness was 2.27 mm (range, 0.2 to 14.0 mm). Eighty-five patients (20.8 percent) had at least one histologically positive sentinel lymph node, and selective lymphadenectomy yielded additional positive lymph nodes in 18 of 84 patients (21.4 percent). Recurrences were noted in 70 patients (17 percent) at a median follow-up period of 31.4 months. Recurrences were more frequent in patients with positive biopsy results (36.5 percent) than in those with negative results (12.1 percent, p < 0.0001). Distant sites of initial recurrence were more likely in the positive group than in the negative group (71 percent versus 49 percent of recurrences, respectively; p = 0.06). The false-negative rate for sentinel lymph node staging was 4.5 percent and overall accuracy was 99 percent compared with clinical follow-up. Disease-free and overall survival correlated significantly with tumor thickness, ulceration, sentinel lymph node status, and the number of tumor-positive lymph nodes (two-sided p < 0.0001 for all comparisons). Multivariable analysis revealed that sentinel lymph node status (p = 0.003), tumor thickness (p = 0.016), ulceration (p = 0.006), and age (p = 0.003) were significant independent predictors of survival for the entire group. Tumor thickness and ulceration were significant predictors of recurrence and survival in sentinel node-negative patients but not in sentinel node-positive patients. Sentinel lymph node histology is possibly the most important negative predictor of early recurrence and survival in patients with American Joint Committee on Cancer stage I and II melanoma. The number of positive lymph nodes provides additional prognostic information. Although sentinel node-negative patients are a prognostically favorable group, various combinations of local and regional recurrences comprise the most common pattern of initial relapse after a negative sentinel lymph node biopsy result.     

Salivary gland lymphocytes in primary Sjogren's syndrome lack lymphocyte subsets defined by Leu-7 and Leu-11 antigens

Primary Sjogren's Syndrome (SS) is an autoimmune disease characterized by dry eyes and dry mouth due to lymphocytic infiltration of lacrimal and salivary glands. Biopsies of their salivary glands provided an opportunity to characterize the phenotypic and functional properties of inflammatory site lymphocytes. We found that the salivary gland lymphocytes (SGL) of SS patients differed from the peripheral blood lymphocytes of the same patients because: a) SGL lacked lymphocytes reactive with anti-Leu-7 and anti-Leu-11 monoclonal antibodies; b) SGL lacked natural killer (NK) activity; and c) SGL lacked the ability to suppress polyclonal B cell responses in the presence of complement fragment C3a, a function that requires the presence of Leu-7+ cells. These studies also showed that the SGL of SS patients differed from tonsillar lymph node (LN) lymphocytes of immunologically normal individuals because tonsillar LN contained Leu-7+ T cells, and tonsillar LN could suppress polyclonal B cell responses in the presence of the complement fragment C3a. The absence of this regulatory subset in the salivary glands of SS patients may contribute to pathogenesis, because these cells may be important in the suppression of polyclonal antibody synthesis and in the elimination of neoplastic or viral infected cells.     

Cytology of leukemic lymphadenopathy

OBJECTIVE: To describe the cytomorphologic features of leukemic cells in lymph node aspiration material. STUDY DESIGN: We studied lymph node fine needle aspiration (FNA) smears of 36 leukemic patients. In 23 cases the lymphadenopathy was noticed simultaneously with marrow leukemia, and in the other 13 cases the lymphadenopathy was noticed during a relapse. Special stains, such as periodic acid Schiff, Sudan Black-B, Oil Red-O and nonspecific esterase, were used in special cases. RESULTS: Thirty-three cases were diagnosed as lymphoma, 1 as extramedullary hematopoiesis and 2 as leukemic involvement. CONCLUSION: Leukemic lymphadenopathy can be misdiagnosed as lymphoma on FNA smears. The clinical findings, previous history, hematologic studies and immunocytochemical studies are essential to the differentiation of leukemic smears from lymphoma. However, in some cases the leukemic infiltration can be diagnosed with certainty, provided that the smears show the characteristic findings, such as Auer rods and neoplastic promyelocytes with azurophilic granules.     

Natural cytotoxicity of lymphocytes from lymph nodes draining breast carcinoma and its augmentation by interferon and OK432

Summary Lymphocytes isolated from axillary lymph nodes draining breast carcinoma were tested for natural killer (NK) activity against K562 in a 4-h ⁵¹Cr-release assay, and the in vitro effects of interferon (IFN) and OK432 (a streptococcal preparation) on their cytotoxicity were examined in comparison with NK activity of autologous peripheral blood lymphocytes (PBL). The levels of NK activity were lower in lymph node lymphocytes (LNL) than in PBL of the same patients. Significant levels of LNL-mediated lysis were recorded in 14 of 42 (33%) lymph node samples and in nine of 14 (64%) patients. Purification of large granular lymphocytes (LGL) from lymph node cells by discontinuous Percoll density gradient centrifugation resulted in an induction or enhancement of cytotoxic activity, with no reactivity in LGL-depleted, small T-lymphocyte populations. Positive reactions were observed with 10 of 13 (77%) LGL samples. The low reactivity of LNL was not attributable to coexistent suppressor cells for NK function, since lymph node cells failed to suppress NK activity of normal PBL. Partially purified human IFN and OK432 augmented NK activity of patients' PBL in approximately 70% and 90% of the cases, respectively, while LNL-mediated lysis was augmented in only 7% and 36% of the lymph node samples by IFN and OK432, respectively. These results indicate that K562-reactive NK cells and/or their precursors may frequently be present at subthreshold levels in the lymph nodes draining breast carcinoma, and that the augmentation of LNL-mediated cytotoxicity by OK432 might provide a local potentiation of natural immune function at the host-tumor interface rather than IFN.     

Prognostic significance of DNA ploidy determined by high-resolution flow cytometry in breast carcinoma

OBJECTIVE: To assess the prognostic value of DNA ploidy in breast carcinoma and its relation to other established prognostic factors. STUDY DESIGN: We evaluated DNA ploidy in 303 breast carcinoma patients with a median follow-up of 63 months. Flow cytometry was performed on frozen tumor material, yielding histograms with narrow peaks (median coefficient of variation of 2.08). DNA ploidy pattern was classified as either diploid versus nondiploid, euploid (diploid and tetraploid) versus aneuploid or diploid/near-diploid (DNA index < 1.2) versus other, and correlated with relapse-free (RFS) and cancer-specific survival (CSS) along with tumor size, histologic grade and type, axillary lymph node involvement, menopausal and steroid receptor status, age and type of treatment. RESULTS: Seventy-one percent of tumors were DNA nondiploid (14% tetraploid and 57% aneuploid). There was a strong association between DNA ploidy and histologic grade. Histologic grade, lymph node status, tumor size and DNA ploidy (regardless of the classification used) were all significantly associated with RFS and CSS in multivariate analysis. CONCLUSION: These results suggest that DNA ploidy, at least when determined from frozen tumor tissue, is an independent prognostic factor in breast carcinoma; however, its prognostic power seems to be inferior to that of histologic grade, with which it strongly correlates.     

Ubiquitin-Specific Peptidase 22, a Histone Deubiquitinating Enzyme,Is a Novel Poor Prognostic Factor for Salivary Adenoid Cystic Carcinoma

Salivary Adenoid Cystic Carcinoma (SACC) is characterized by a high rate of local recurrence and infiltration, strong invasion to peripheral nerves or late distant metastasis. Our aim was to investigate the expression of Ubiquitin-specific protease 22 (USP22) in SACC patients and its possible relationship to the outcome of the disease. A total of 135 SACC tissues and adjacent non-cancerous tissues which were diagnosed between 2002 and 2007 were enrolled in this study. Immunohistochemistry was used to compare the expression pattern of USP22 in SACC and adjacent non-cancerous groups, and the prognostic significance was assessed by Kaplan-Meier analysis and Cox proportional hazards regression in SACC patients. The rate of high expression of USP22 was significantly higher in SACC group than that in adjacent non-cancerous group. High expression of USP22 was significantly correlated with histological subtype, lymph node metastasis, grade, Ki-67 and SOX2 expression. Furthermore, USP22 acts as an oncogene by regulation the BMI-1 pathway and c-Myc pathway. SACC patients with high USP22 expression showed the poorer overall survival (OS) and disease-free survival (DFS) than those patients with low USP22 expression. In multivariate analysis, only lymph node metastasis and USP22 expression were the independent prognostic factors for OS and DFS in SACC. Our study provides evidence that USP22 expression is an independent prognostic factor for SACC patients.     

淋巴结转移率对胃癌预后价值的评价

目的:评价淋巴结转移率(MLR)对胃癌术后患者预后的预测价值。方法:回顾性分析2004年至2006年间在我院就诊,临床资料完整的363例胃癌术后患者。按照第七版UICC/TNM(pN分期)及淋巴结转移率两种方法对淋巴结进行分期,比较两种方法评价胃癌预后的准确性及适用性,确定MLR分期方法的特点及优势。结果:363例胃癌术后患者按单变量生存分析方法将淋巴结转移率(MLR)分为四期:MLR0(0.0%)、MLR1(0-30%)、MLR2(30-70%)、MLR3(≥70%),其5年生存率分别为84.9%、58.3%、28.7%、12.9%,有显著性统计学差异(P<0.001)。pN分期分为pN0、pN1、pN2、pN3a、pN3b,其5年生存率分别为84.9%、60.8%、32.0%、21.9%、6.8%,有显著性统计学差异(P<0.001)。单因素COX生存分析后显示,MLR分期越高,预后越差(HR:MLR1,MLR2,MLR3/MLR0=1.589,4.455,9.900,P<0.001)。按清除淋巴结个数将所有病例分成两组:group1(≤15个)、group2(>15个),在该两组中比较pN及MLR分期的预后,结果显示pN3a在group1组中的5年生存率明显低于group2组(6.2%vs.38.4%,P<0.001),而MLR分期与清除淋巴结个数无统计学生存相关差异(P>0.05)。COX比例风险模型多因素分析表明,pN分期、MLR分期、肿瘤浸润深度、肿瘤分化程度均为影响预后的独立因素,以pN及MLR分期风险比最高。结论:MLR分期是评价胃癌术后患者预后的独立因素,该方法不受淋巴结清扫个数的影响,与pN分期方法相比,实用、准确、简单,可以降低pN分期因淋巴结清扫不足造成的期别转移现象。     

The therapeutic effect of OK-432-combined adoptive immunotherapy against liver metastases from gastric or colorectal cancers

Twenty-four patients with liver metastases from gastric or colorectal cancer were treated with OK-432-combined adoptive immunotherapy (AIT). Lymphocytes isolated from regional lymph nodes or peripheral blood were cultured with medium containing T cell growth factor and sonicated tumor extract antigen (SE-Ag) for 9–13 days. The cultured lymphocytes were transferred mainly through the hepatic artery after the administration of OK-432, a streptococcal preparation. Sixteen of the 24 patients received a low dose of anti-cancer agents between the OK-432 injection and cell transfer. When cultured without SE-Ag, regional lymph node lymphocytes (RLNL) showed significantly (P<0.05) higher cytotoxic activity against autologous tumor cells and, on the contrary, lower cytotoxic activity against K562 than peripheral blood lymphocytes (PBL). When cultured with SE-Ag, cytotoxicity of RLNL against autologous tumor cells was nearly equivalent to that of PBL. The blastogenesis of fresh PBL to SE-Ag was significantly (P<0.05) augmented after the OK-432-combined AIT. Two patients showed complete response and 4 patients showed partial response among 19 patients who had evaluable lesions. Five patients whose liver metastases were resected were treated with OK-432-combined AIT as an adjuvant therapy. To date they are alive without recurrence in the liver.Abbreviations AIT adoptive immunotherapy - RLNL regional lymph node lymphocytes - SE-Ag sonicated tumor extract antigen     

老年宫颈癌50例临床及预后分析

目的：探讨老年宫颈癌的临床病理特征及预后影响因素。方法：对50例老年宫颈癌患者的临床特点及生存情况进行回顾性分析。结果：鳞状细胞癌45例（90．0％）,腺癌4例（8．0％）,透明细胞癌1例（2．0％）;≤Ⅱa期占16．0％,≥Ⅱb期占84．0％;主要临床症状为绝经后不规则阴道流血,全组1、3、5年生存率分别为82．0％,66．0％,54．0％。多因素分析结果显示病理类型、临床分期及淋巴结转移情况是老年宫颈癌患者预后的独立影响因素（均P〈0．05）。结论：KPS评分≥70分、鳞癌、临床分期为Ⅰ期、Ⅱ期,无淋巴结转移的患者预后较好,病理类型、临床分期及淋巴结转移情况是老年宫颈癌患者预后的独立影响因素。     

Immunophenotyping--a tool for the differential diagnostics of lymphadenomegaly

BACKGROUND: Flow cytometry is a method that enables the automated quantification of a set of parameters for a large number of cells or cell-like particles. It is also possible to analyze solid tissues after reduction to a single cell suspension. One of the applications of fl ow cytometry is immunophenotyping. AIM: The authors try to introduce the basic physical and biological principles of fl ow-cytometry to the broader public and to prove the benefits of method in lymph nodes assessment. METHOD: A common method of immunophenotyping with the help of labeled monoclonal antibodies applied to lymph node cells was used. RESULTS: Flow cytometry revealed the infiltration of the extirpated lymph node with leukemic cells. CONCLUSIONS: The authors demonstrate fl ow cytometry as a relatively less common but efficient way of lymph node assessment in a patient with an anamnesis of acute lymphoblastic leukemia. They also discuss the contribution of immunophenotyping to the process of the differential diagnostics of lymph nodes enlargement.     

Evaluation of extra capsular lymph node involvement in patients with extra-hepatic bile duct cancer

ABSTRACT: BACKGROUND: Lymph node metastasis (LNM) is one of the most important prognostic factors for extra-hepatic bile duct carcinoma (ExHBDC). Extra capsular lymph node involvement (ExCLNI) is the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The prognostic impact of ExCLNI has been shown to be mainly significant in head and neck malignancies. Recently, the prognostic impacts of ExCLNI have been evaluated in gastrointestinal malignancies. However, no data are available regarding the incidence and prognostic significance of extra-capsular lymph node involvement (ExCLNI) in resectable ExHBDCs. The aim of the present study is first to evaluate the incidence of ExCLNI in surgically-treated ExHBDCs and, second, to determine the prognostic impact of ExCLNI in patients with surgically-treated ExHBDCs. METHODS: A total of 228 patients, (110 cases of hilar cholangiocarcinoma and 118 cases of distal cholangiocarcinoma), with surgically-treated ExHBDCs were included in this retrospective study. ExCLNI was defined as the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The existence of ExCLNI and its prognostic value were analyzed as a subgroup of lymph node metastasis. RESULTS: ExCLNI was detected in only 22% of patients with lymph node metastasis of surgically-treated ExHBDC. The presence of ExCLNI correlated with distal cholangiocarcinoma (P = 0.002). On univariate analysis for survival, perineural invasion, vascular invasion, histological grade, and lymph node metastasis were statistically significant factors. On multivariate analysis, only lymph node metastasis was identified as a significant independent prognostic factor in patients with resectable ExHBDC. Subgroups of lymph node metastasis including the presence of ExCLNI, location of lymph node metastasis, and the number of lymph node metastasis had no statistically significant impact on survival. CONCLUSION: ExCLNI was present in only 22% of the LNM (7% of overall patients) in patients with surgically-treated ExHBDCs. And ExCLNI would have no impact on the survival of patients with surgically-treated ExHBDCs.     

Evaluation of basic procedures for adoptive immunotherapy for gastric cancer

Peripheral blood lymphocytes (PBL) of gastric cancer patients in advanced stages showed lymphokine activated killer (LAK) activities comparable to those of healthy donors, suggesting potential applicability of LAK cells induced from PBL stimulated with recombinant interleukin-2 (rIL-2) in adoptive immunotherapy (AIT) for gastric cancer. In order to generate a large number of LAK cells from PBL, lymphocytes were cultured with both rIL-2 and phytohemagglutinin (PHA). In this culture, the numbers of cells increased to a greater extent than those in culture with rIL-2 alone but cytotoxic activity did not augment, thus suggesting that this procedure would not afford sufficient clinical effects. On the other hand, a large number of LAK cells with high anti-tumor activities were efficiently induced from spleen cells of the patients by culture of rIL-2; hence clinical usefulness of these LAK cells is anticipated. In regional lymph node lymphocytes (RLNL) cultured with rIL-2, the cytotoxic activities were lower than in those induced in PBL, and a characteristic increase of CD8 + CD11 + suppressor T cells was observed after incubation with rIL-2. Nevertheless, an increase of CD4 + 4B4⁺ helper inducer T cells was also observed in RLNL after the culture with rIL-2. Furthermore, high cytotoxic activities were induced in RLNL in some cases in which metastasis to the regional lymph nodes was not detected. When gastric cancer patients were pretreated with biological response modifiers (BRM), especially with Lentinan, LAK cells from PBL showed higher NK and LAK activities as compared with those of patients without BRM pretreatment.This work was partly supported by a grant from Hokkoku Cancer Research Foundation.     

淋巴结转移阴性的胃癌患者临床病理特征及生存探讨

目的:探讨淋巴结转移阴性胃癌患者的临床病理特征以及预后影响因素。方法:收集2000年1月至2009年1月我院收治的胃癌患者325例,其中经病理检查显示淋巴结转移阴性的105例患者作为阴性组(LN-组),另229例阳性患者作为阳性组(LN+组),比较两组的临床病理特征及临床预后。结果:LN-组的肿瘤直径、浸润深度及术后化疗与LN+组比较差异显著(P0.05);LN-组的5年生存率为76.2%,显著高于LN+组的43.2%(P0.05)。未透浆膜的LN-患者3年、5年生存率显著高于浸透浆膜者,术后化疗的LN-患者5年生存率显著高于未化疗者(P0.05),肿瘤直径5 cm的LN-患者3、5年生存率显著高于≥5 cm者(P0.05)。单因素分析显示浸润深度、肿瘤大小及术后化疗与LN-胃癌患者的预后具有密切关系(P0.05)。COX多因素分析显示浸润深度是影响LN-胃癌患者临床预后的独立因素(P0.05)。结论:淋巴结转移阴性胃癌患者的病灶多位于中下部,男性多于女性,发病年龄多在60岁以内,肿瘤直径多不超过5 cm,浸润深度多未浸透浆膜,临床预后优于淋巴结转移阳性胃癌患者,浸润深度是影响淋巴结转移阴性胃癌患者临床预后的独立因素。     

Limb lymph node response to bone fracture

In previous clinical studies, dilation of afferent lymphatics and enlargement of inguinal lymph nodes (LN) were observed in lymphoscintigrams from patients with persistent posttraumatic edema of lower extremities after fractures and trauma of soft tissues. In this study, changes in rat popliteal and iliac lymph nodes draining lymph from the site of tibial fracture and adjacent soft tissue injury were investigated. The observed parameters were lymph node weight, cell number, phenotype frequency, cell cytokine expression, and reactivity to mitogens. The key observations included: a) increase in the weight and total cell number of the lymph nodes; b) increased autotransformation rate and responsiveness of lymph node cells to mitogen; c) decreased frequency of ED1 macrophages and activated OX8 cytotoxic cells in flow cytometry analysis; d) high expression of OX6 class II-positive, OX7 (stem cells), OX62 (migrating dendritic cells), ED1 (macrophages), and OX12 (B cells) on immunohistochemical sections of LNs with some few HIS48 (granulocytes); e) high expression of NOS3 and TGF beta by lymph node lymphocytes and endothelial cells. In summary, local lymph nodes reacted to internal wounds, such as bone fracture and injury to adjacent tissues, through mobilization of cells from the blood circulation, along with activation of cellular subsets. The molecular mechanism that provides the signal for this reaction remains unknown. The absence of major changes in the frequency of lymph node cell subpopulations indicates that lymph nodes are constitutively prepared for influx of antigens from damaged tissues and react only with increase in cell number and cell activation. The nature of the reaction, including lack of immunization against autoantigens, remains unclear. Further elucidation will require studies on the mechanism of cross-tolerance to self-antigens during wound healing.