Immunomorphologic study of regional lymph nodes in cancer: Response of regional lymph node cells from gastric and colorectal cancer to PHA stimulation

To obtain information regarding the immunologic capacity of uninvolved regional lymph nodes (RLNs) draining tumor, the in vitro response of regional lymph node cells (RLNCs) to PHA was investigated in lymph nodes from 55 patients with gastric or colorectal cancer, and gastric ulcer. Evaluation of data relative to cancer progress demonstrated that, in gastric cancer patients, the response of stimulated RLNCs from patients with middle stage carcinoma was significantly higher compared with those of cells from patients with early or late stage carcinoma, such being similar to the response of RLNCs from control patients with gastric ulcer. The results from colorectal cancer patients were also similar to those from patients with gastric cancer. Our results suggest that RLNs without metastasis contain cells capable of responding to PHA despite the presence of growing tumors in these cancer patients. In the results of PHA stimulation in relation to the lymph node morphology, we observed in both groups of patients with gastric or colorectal cancer that, regardless of the extent of the cancer lymph nodes with lymphocyte predominance there was a high PHA response while lymph nodes with lymphocyte depletion and unstimulated nodes exhibited a low PHA response. These results show a close relationship between this lymph node morphology and immunologic status of nodes.     

进展期胃癌淋巴结清扫范围的研究进展

一个多世纪以来,胃癌的手术治疗存在诸多争议,尤其是进展期胃癌的淋巴结清扫范围是争论的焦点问题.本文就当前国内、外有关胃癌淋巴结清扫范围的研究报道及最新进展做一综述和分析.     

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目的探讨甲状腺微小癌(TMC)颈淋巴结转移规律,指导TMC颈淋巴结的恰当处理。方法回顾性分析济南军区总医院1999年1月至2010年5月行颈淋巴结清扫的117例TMC病人颈淋巴结转移情况,分析TMC局部淋巴结转移的特点、影响因素、诊断方法及处理意见。结果淋巴结转移发生率53.8%(63/117)。常见颈部淋巴结转移部位依次为Ⅵ区(47.9%)、Ⅲ区(20.9%)、Ⅳ区(16.5%)、Ⅱ区(6.1%)。随Ⅵ区淋巴结转移个数增多,侧方淋巴结转移递增。肿瘤数目、大小不同淋巴结转移发生率差异有统计学意义(P=0.000,P=0.014)。超声检查判断淋巴结有无转移的敏感性、特异性和准确性分别为19.0%、98.1%和55.5%。术中淋巴结快速病理检查有13.8%假阴性。全组无复发、转移和死亡。结论 TMC区域淋巴结转移发生率较高,应重视术前评估和术中快速活检,掌握TMC淋巴结转移特点,有助采取恰当手术方式,有选择的预防性区域性颈淋巴清扫可为可使病人获益。     

Analysis of tissue lymphocytes by double fluorescent staining —Gastric cancer tissue and regional lymph nodes—

An immunohistochemical study was perforrmed on human lymphocytes in the tissue of gastric cancer, and also in the regional lymph nodes, by double fluorescent staining, using monoclonal antibodies. Leu3a⁺8⁺ cells (induct T cells) which consist about 30 per cent of Leu 3a⁺ cells were seen in the tissue surrounding the gastric cancer. The other 70 per cent Leu 3a⁺ cells were Leu3a⁺8⁻ cells (helper T cells). In the lymph nodes they were noted in T cell areas in almost the same proportions, while in germinal centers, only Leu3a⁺8⁻ cells were found. On the other hand, OKT8⁺Leu15⁻ cells (cytotoxic T cells) were noted in a large number, while OKT8⁺Leu15⁺ cells (suppressor T cells) were few. Further, an increase of OKT8⁺Leu15⁻ cells was seen around gastric cancer or metastatic cancer in lymph nodes. These immunohistochemical findings suggest that cytotoxic T cells are the main component in the tissue of gastric cancers and the regional lymph nodes. Increases in inducer T cells and helper T cells are probably required to induce cytotoxic T cells around the cancer tissue.     

Effects of the oral or intratumoral administration of OK432 on the immuno-reactivities of regional lymph nodes in gastric cancer patients

The effects of OK432, a streptococcal preparation, administered either orally (PO-OK432) or intratumorally (IT-OK432) on the immuno-reactivities of regional lymph nodes were investigated in gastric cancer patients. Although native lymph node lymphocytes (LNL) from untreated patients did not show any cytotoxicities against K562 and Raji cells, enhanced activities were found in LNL from patients administered OK432. Augmenting effects on the cytotoxicities of LNL byin vitro additional OK432, interleukin 2 or γ-interferon were remarkable in the patients given IT-OK432. Moreover, the cytotoxicities of peripheral blood lymphocytes were augmentedin vitro more strongly in patients given IT-OK432 than in those given PO-OK432. Flow cytometric analysis of LNL revealed a decrease in CD4⁺ cells by PO-OK432 and an increase in CD8⁺ cells by IT-OK432. An increase in CD4⁺2H4⁺ cells and a decrease in CD4⁺2H4⁻ cells were observed in the patients given OK432, though CD8⁺CD11⁺ cells decreased by PO-OK432 while CD8⁺CD11⁺ cells increased by IT-OK432. Thus, it is suggested that LNL reactive to OK432 immunotherapy may differ between PO- and IT-OK432, and that the immunoreactivities of local lymph nodes and systemical immuno-reactivities may be highly potentiated by IT-OK432 rather than PO-OK432.     

Analysis of regional lymph nodes in periprostatic fat following robot-assisted radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? A few publications have reported on the presence of lymph nodes in the anterior prostate lymphofatty tissue. This is important as increasing emphasis is placed on extending the overall limits of lymph node dissection in prostate cancer. For a large group of patients treated with robotic prostatectomy we continue to routinely remove and examine this tissue in order to provide additional staging information for patients. In a comprehensive cancer centre, the long‐term oncologic ramifications of excising tumour containing lymph nodes will continue to be studied.

OBJECTIVE

? To determine the incidence and significance of lymph nodes in the anterior prostatovesicular lymphofatty tissue.

PATIENTS AND METHODS

? One hundred and twenty patients with clinically localized prostate cancer underwent robot‐assisted laparoscopic radical prostatectomy with excision of anterior prostatovesicular tissue at a single institution over a 6‐month period. ? Tissue was sent for pathological analysis. ? Separate pelvic lymph node dissection was carried out in moderate‐risk and high‐risk patients.

RESULTS

? A total of 20 out of 120 patients (16.7%) had lymph nodes in the anterior lymphofatty tissue. ? Average lymph node number when present was 1.5 (one to three). ? Pathological assessment of the lymph nodes revealed metastatic prostate cancer in 3 out of 120 (2.5%) patients, each of whom had adverse pathological features. ? Patients with metastatic lymph nodes in the anterior tissue did not have cancer involvement of the pelvic lymph nodes. ? Patients with lymph nodes found in the anterior lymphofatty tissue were slightly younger but were otherwise similar with respect to other demographics, prostate‐specific antigen, biopsy Gleason score, clinical stage, pathological stage, pathological Gleason score, seminal vesicle invasion, and margin status.

CONCLUSIONS

? Anterior lymphofatty tissue overlying the prostate occasionally contains lymph nodes that can harbour malignant disease and routine excision may eradicate regional tumour burden. ? Of patients with nodes, 15% were found to have malignant involvement. ? The long‐term impact on progression‐free and overall survival requires further study.     

淋巴结转移度与结直肠癌预后关系研究

目的 探讨淋巴结转移度（LNR）与结直肠癌术后5年无病存活率和总存活率的关系。 方法 对2000年1月至2004年4月北京大学人民医院胃肠外科行根治性手术治疗的124例结直肠癌进行分析。将124例Ⅲ期结直肠癌依据LNR分为3组: LNR＜0.167、LNR≥0.167~＜0.562、LNR≥0.562,比较组间预后差异。分析诸临床病理因素与结直肠癌预后之间的关系。 结果 LNR和转移淋巴结数目均与结直肠癌术后5年无病存活率和总存活率相关,而LNR是总存活率的独立相关因素。对淋巴结病理检查数目未超过12枚的病例,LNR与5年无病存活率相关。 结论 LNR与Ⅲ期结直肠癌的预后相关;对伴淋巴结转移的结直肠癌,特别是淋巴结病理检查数目相对较少的病例,应考虑将LNR作为临床病理分期的补充。     

结直肠癌前哨淋巴结转移相关蛋白的蛋白组学研究

目的 筛选前哨淋巴结(SLN)中与结直肠癌早期转移相关的蛋白质.方法 术中取43名结直肠癌早期患者的SLN及对应的正常淋巴结(NLN).提取SLN和NLN两组总蛋白后行双向凝胶电泳和质谱法对差异蛋白进行筛选和鉴定.用蛋白质印迹法和免疫组织化学法对其中的转移相关蛋白行进一步研究.结果 两组间检测出40种差异表达的蛋白质,SLN中表达升高且与转移相关的蛋白分别为核不均一核糖核蛋白A1( hnRNP A1)、埃兹蛋白(Fzrin)、微管蛋白β-2C (tubulin β-2C)和膜联蛋白A1(Annexin A1).蛋白定量结果显示两组间4种蛋白表达差异有统计学意义(P＜0.05).结论 结直肠癌SLN与NLN蛋白表达存在差异.筛选出的4种转移相关蛋白可能成为结直肠癌早期淋巴转移的标志物.     

肺癌淋巴结廓清程度对手术根治性的评价

作者近９年来，对３８６例肺癌患者施行了手术切除。术中按成毛韶夫肺癌淋巴结分布图对肺门和同侧纵隔淋巴结进行了广泛廓清。共清除淋巴结２６０３组，平均每例清除６．７４组。淋巴结转移率为４９．２％（１９０／３８６）。单纯Ｎ１４３例，占１１．１％；Ｎ２（包括Ｎ１＋Ｎ２）１４７例，占３８．１％。Ｎ２转移率在鳞癌、腺癌、小细胞癌及大细胞癌分别为３０．１％、４４．１％、４８．０％及５０．０％。肺癌淋巴结转移具有跳跃性和多发性。作者强调只有广泛清除了肺内和纵隔淋巴结才有可能达到根治，否则应被视为非根治术。     

The clinical relevance of positive sentinel nodes only versus positive nonsentinel lymph nodes in breast cancer patients

BACKGROUND: The purpose of this study was to determine the difference in clinical outcomes for patients with histologically positive sentinel lymph nodes (SLN+) compared with patients with histologically positive nonsentinel second echelon lymph nodes (NSLN+). METHODS: Eight hundred thirteen node positive patients from a prospectively accrued database of 3200 patients who underwent sentinel node mapping were evaluated. In all, 506 of the 813 patients (62%) were SLN+ only and 307 of the 813 patients (38%) were SLN+ plus at least one NSLN+. Patients' overall survival and disease-free survival were obtained and statistical analyses performed comparing the two groups. RESULTS: As the number of NSLN+ increased, there was a significant difference in disease-free survival (P = 0.001) and overall survival (P = 0.003) between those patients who had 0 to 4 NSLN+ and those who had 5 or more NSLN+. The SLN+ only patients did not show significant differences with respect to survival, based on the number of SLN+ (overall survival, disease-free survival; P = 0.742). CONCLUSIONS: The survival (overall survival, disease-free survival) for patients with 3 or more SLN+ was not statistically different than for patients with 1 or 2 SLN+ (P = 0.742). However, an alteration of biologic behavior was observed when multiple NSLN+ contain metastatic breast cancer. Involvement of 5 or more NSLN+ portends a significantly (P = 0.001) worse prognosis, regardless of the number of SLN+.     

乳腺癌行腋窝淋巴结清扫规范、争议与共识

乳腺癌的有效治疗方法很多,但外科手术是公认的乳腺癌治疗的基础。手术成功与否的最根本标志是肿瘤手术区域的局部控制。腋窝淋巴结受累的程度是预测乳腺癌术后复发和生存,指导进一步个体化治疗的最为重要指标。规范的腋窝淋巴结清扫和病理检查对乳腺癌的治疗至关重要。术前判断存在腋窝淋巴结转移的乳腺癌病人,腋窝淋巴结清扫是乳腺癌手术的规范和要求。术前临床诊断无腋窝淋巴结转移（cN0）的早期乳腺癌病人,如果前哨淋巴结活检阴性可不做进一步的腋窝淋巴结清扫也已成为共识。对于前哨淋巴结1或2枚阳性的乳腺癌病人可以不行腋窝淋巴结的清扫的观点仍然存在争论。     

The appropriate number of negative lymph nodes dissection for nonmetastatic penile cancer

Negative lymph nodes status has been attached more attention as a prognostic indicator for nonmetastatic penile cancer. We aimed to identify the appropriate number of negative lymph nodes dissection for nonmetastatic penile cancer using the Surveillance, Epidemiology and End Results database. A total of 1,470 nonmetastatic patients with penile squamous cell carcinoma were identified during 2004 and 2013. All patients were categorised according to different risk levels and lymphadenectomy. Univariate and multivariate Cox regression analyses were performed to evaluate the relationship between prognostic risk factors and cancer‐specific survival. The optimal cut‐off value of negative lymph nodes dissection was determined using the X‐Tile program. A total of 1,470 patients were categorised into low‐ (pT1G1), intermediate‐ (pT1G2) or high‐risk (pT1G3 and all higher stages) groups. In multivariate Cox analysis, lymphadenectomy improved the cancer‐specific survival for patients in high‐risk group (p = 0.014). Further, the optimal cut‐off value of negative lymph nodes dissection for high‐risk patients was 5 and patients with >5 negative lymph nodes had a higher cancer‐specific survival (χ² = 9.3676, p < 0.05). Therefore, lymphadenectomy improved survival for high‐risk penile cancer and the removal of more than five negative lymph nodes was correlated with higher cancer‐specific survival for high‐risk patients who underwent lymphadenectomy.     

Non-invasive and minimally invasive staging of regional lymph nodes in penile cancer

Introduction  The management of the regional lymph nodes in penile cancer patients, particularly when these lymph nodes are impalpable, remains controversial. Prophylactic bilateral inguinal lymphadenectomy is associated with high morbidity and is often unnecessary. However, there is no non-invasive or minimally invasive staging technique that can determine the lymph node status of penile cancer patients with 100% accuracy. Methods  We reviewed the current literature to examine the role of non-invasive and minimally invasive techniques for staging regional lymph nodes in penile cancer with particular reference to clinically impalpable disease. Results  Cross-sectional imaging (un-enhanced CT and MRI) modalities have a role in the assessment of patients with palpable inguinal basins and in locating distant metastases, but are unreliable in staging impalpable regional lymph nodes. The spatial resolution of lymphotropic nanoparticle enhanced MRI (LNMRI) and positron emission tomography (PET)/CT are limited to several millimetres and so these modalities cannot reliably detect micro-metastases (<2 mm). Ultrasound (US) and fine-needle aspiration cytology (FNAC) are indicated in staging palpable inguinal basins but are unreliable in isolation in the assessment of impalpable lymph nodes. They are, however, useful as an adjunct to dynamic sentinel lymph node biopsy (DSLNB) in lowering false-negative rates. Conclusions  While we await staging modalities that can equal the results of DSLNB with fewer disadvantages, histological staging in the form of DSLNB remains the best minimally invasive staging modality we can offer at risk patients presenting with clinically node negative groins.     

Positive sentinel lymph node biopsy predicts the number of metastatic axillary nodes of breast cancer

It remains to be clarified whether a positive sentinel lymph node biopsy (SLNB) can predict the number of metastatic axillary nodes. This study examined a consecutive series of women with unilateral invasive breast cancer who underwent axillary lymph node dissection after an intra-operative positive SLNB. The numbers of positive and negative sentinel lymph nodes (SLNs) were analyzed for a likelihood of pN1a, pN2a, and pN3a diseases as per the UICC TNM classification. Of the 368 study patients, 165 (45%) had one positive SLN and one or more negative SLNs. This result represented the most common combination of positive and negative SLNs. It was also the most predictive indicator (93%) of pN1a disease and the least predictive indicator (7% or 0%) of pN2a or pN3a disease, respectively. The numbers of positive and negative SLNs can predict the number of metastatic axillary nodes in breast cancer patients.     

Cancer biology and necrotic changes in metastatic lymph nodes and survival of colon cancer patients

BACKGROUND: Identifying factors that can contribute to a better understanding of tumor progression in stage III colon cancer patients continues to be an important task. Necrotic changes in metastatic lymph nodes have not been previously analyzed in English literature. METHODS: The study included 48 consecutive colon and rectosigmoid cancer patients with stage III disease who underwent radical surgery. After reviewing the diagnostic slides, a pathologist developed a scale describing the extent of necrotic changes. Results were evaluated using Kaplan-Meier method and log-rank test. RESULTS: Thirty-four (70%) patients had necrotic changes in metastatic lymph nodes. Patients with necrotic changes in metastatic lymph nodes had more risk factors than patients without necrosis. The 5-year survival rate for patients with necrotic changes in metastatic lymph nodes was 85% and for patients without necrosis was 50% (P = 0.02). CONCLUSIONS: The survival of patients with necrotic changes in metastatic lymph nodes was higher (P = 0.02). These necrotic changes can help us to understand body-tumor relations.     

膀胱癌盆腔淋巴结转移的影像学诊断

膀胱癌是泌尿系统最常见的恶性肿瘤,易发生复发、转移。相对于淋巴结转移阴性的患者,淋巴结转移阳性的患者复发、转移概率更高,而且往往是致死性的。准确预测淋巴结转移与否对于患者治疗策略的选择具有重要指导意义。目前诊断淋巴结转移的金标准为术后病理,术前主要依靠影像学,但是准确性不太理想。本文就膀胱癌盆腔淋巴结转移的影像学诊断方法,包括CT、MRI及PET/CT、SPECT/CT及前哨淋巴结显像等作一综述。     

A three-step method for modular lymphadenectomy in gastric cancer surgery: The ability to retrieve sufficient lymph nodes and improve survival

Background

Systematic lymphadenectomy for the resection of sufficient lymph nodes is the most important part of curative resection in gastric cancer surgery. Here, we explore the outcomes of the three-step method for modular lymphadenectomy (TSMML) and determine its safety and efficacy, compared with the conventional method for lymphadenectomy (CML).

Assessing the minimum number of lymph nodes needed at radical cystectomy in patients with bladder cancer

OBJECTIVE

To identify the likelihood of finding one or more positive lymph nodes (LNs) according to the number of LNs removed at radical cystectomy (RC), as the number of LNs removed affects disease progression and survival after RC.

PATIENTS AND METHODS

Between 1984 and 2003, 731 assessable patients had RC and bilateral pelvic lymphadenectomy at three different institutions. ROC curve coordinates were used to determine the probability of identifying one or more positive LNs according to the total number of removed LNs.

RESULTS

Of the 731 patients, 174 (23.8%) had LNs metastases. The mean (median, range) number of LNs removed was 18.7 (17, 1–80). The ROC coordinate‐based plots of the number of removed LNs and the probability of finding one or more LNs metastases indicated that removing 45 LNs yielded a 90% probability. Conversely, removing either 15 or 25 LNs indicated, respectively, 50% and 75% probability of detecting one or more LNs metastases.

CONCLUSIONS

These data indicate that removing 25 LNs might represent the lowest threshold for the extent of lymphadenectomy at RC. Our findings confirm the importance of an extended lymph node dissection.