A population-based atlas and clinical target volume for the head-and-neck lymph nodes

PURPOSE: To develop a population-based three-dimensional lymph node target volume of the head and neck. METHODS AND MATERIALS: The T2 weighted axial magnetic resonance imaging (MRI) images of 35 patients with known head and neck cancer were reviewed. An experienced head and neck radiologist marked each lymph node (LN) electronically. The images were distributed to one of 12 axial levels of the head and neck with each level representing a distinct portion of the neck based on external contours and the presence of anatomic structures. The LNs were marked with five different symbols to distinguish the superior/inferior extent of each LN within each level. With the categorization of each image into a different superior/inferior level of the neck, the registration of the images was limited to two dimensions. Nonlinear transformation accounted for inter-patient differences although no local warping was used. The co-registration used recognizable anatomic landmarks (vertebral body, mandible, maxilla, clivus as well as the sternocleidomastoid muscle, external skin contour, spinal cord) to match the patient anatomy. RESULTS: In total, 503 images were co-registered with the baseline images. The majority of the co-registrations were of good quality; 361, 122, and 20 image co-registrations scored as global, limited, and poor co-registrations respectively. One thousand and fifty seven LNs were marked, with 122 LNs marked as submandibular and submental LN. Among the levels A, B, C, D, E, F, G, H, 22, 44, 206, 199, 196, 175, 63, 35 LN were marked respectively. Noteworthy anatomic variation was observed among the different nodal groups that are summarized in the representative baseline images. CONCLUSIONS: Image registration of a series of head and neck images generates a valuable population-based lymph node map that can be used to guide the three-dimensional delineation of the elective lymph node target volume. Significant variation in the lymph node location was seen in all LN groups. The medial border of the internal jugular vein can be used as an important landmark structure in delineating the jugular LN clinical target volume and, for that reason, intravenous contrast is recommended to improve visualization. The location of the submandibular LN appear to be limited to the space anterior and lateral to the submandibular gland and are found mostly along the inferior edge of the mandible. The location of the retropharyngeal LN does vary but their location does not appear to vary with any other recognizable axial structure. The lymph node map provides another collaborating piece of evidence in defining the head and neck LN clinical target volume.     

结直肠癌单个转移淋巴结分布情况及其临床意义

目的：回顾研究结直肠癌单个转移淋巴结的分布情况,预测结直肠癌中前哨淋巴结（SLN）概念的适用性及分布情况,并为进一步结直肠癌SLN的前瞻性研究提供参考。方法：收集中山大学附属肿瘤医院腹科1998年1月～2003年9月根治术后常规病理检测只有一个淋巴结转移的125例结直肠癌患者有关资料。其中男67例（53．3％）,女58例（46．5％）;平均年龄55．8岁（25～82岁）。结果：125例患者共计淋巴结1065枚,平均每例患者8．52枚（1～32枚）。单个转移淋巴结分布情况结果显示肠旁组淋巴结转移81例（64．8％）,中间组淋巴结转移40例（32．0％）,中央组淋巴结转移4例（3．2％）。非肠旁组织转移的“跳跃”转移44例（35．2％）。结论：大部分结直肠癌SLN分布于肠旁,但相当部分可出现“跳跃”现象。必须进行深入的前瞻性研究,探索理想的结直肠癌SLN示踪方法,全面研究结直肠癌SLN的分布规律。     

远端胃癌淋巴结转移规律及临床意义*

目的：探讨远端胃癌各组淋巴结转移的特点,指导远端胃癌根治手术中淋巴结清扫的范围。方法：回顾性分析2010年2 月至2014年9 月天津医科大学肿瘤医院远端胃癌患者773 例接受D 2（D 2 +）胃次全切除术的临床病理资料,分析其淋巴结转移特点。结果：773 例远端胃癌患者术后病理证实淋巴结转移为423 例（54.72%）,各组淋巴结中发生转移的患者所占比例由高至低依次为NO.6、NO.3、NO.4sb 、NO.5 组淋巴结。N 1 淋巴结转移率由高至低依次为NO.3、NO.6、NO.5、NO.4d 组淋巴结;N 2 淋巴结转移率由高至低依次为NO.8a 、NO.7、NO.1 组淋巴结。50.68% 的患者出现NO.8a 组淋巴结跳跃性转移。结论：远端胃癌根治性手术应注意NO.8a 淋巴结转移的可能性,必要时应适当扩大淋巴结的清扫范围。     

乳腺癌组织与腋窝淋巴结中乳腺球蛋白的表达及其临床意义

目的:探讨乳腺球蛋白(MAM)在乳腺癌组织和腋窝淋巴结中的表达及其临床意义。方法:应用免疫组化法和RT-PCR法检测乳腺癌组织、非乳腺癌组织、乳腺癌腋窝淋巴结的MAM和MAM mRNA表达。结果:(1)MAM在乳腺癌组织表达的敏感度为88.8%,特异度为89.3%。MAM在乳腺癌组织和非乳腺癌组织中表达的差别有统计学意义(P<0.01)。(2)MAM的阳性表达与ER、PR状态(P=0.022和0.010)、组织分级(P=0.012)有关,与诊断时肿瘤大小、有无淋巴结转移、C-erbB-2状态、年龄无关。(3)MAMmRNA在乳腺癌腋窝淋巴结表达的灵敏度为90%,特异度为68.7%,阳性预测值为64.3%,阴性预测值为91.7%。结论:MAM是乳腺癌敏感且特异的标志物之一,有助于判断腋窝淋巴结转移存在。     

乳腺癌前哨淋巴结微转移的检测与临床意义

前哨淋巴结(SLN)活检能够准确评估区域淋巴结状态,为乳腺癌患者提供精确的分期,同时也减轻了淋巴结阴性患者的手术并发症.规范前哨淋巴结病理检测手段,充分利用分子生物学检测方法,有助于准确判断微转移.但前哨淋巴结的微转移在乳腺癌预后判断、治疗决策中的意义尚存争议.     

pN1a甲状腺乳头状癌中央区淋巴结清扫数与临床转归的关系

背景与目的:甲状腺乳头状癌(papillary thyroid carcinoma,PTC)常发生颈部淋巴结转移,多见于颈部中央区.该研究旨在探讨转移淋巴结数小于等于5枚的pN1a PTC患者颈部中央区淋巴结清扫数与131I"清甲"治疗后临床转归的关系.方法:回顾性分析2012年2月—2014年12月北京协和医院收治的167例经术后病理证实存在1~5枚淋巴结转移的pN1a PTC患者的临床资料,均行全甲状腺切除或近全甲状腺切除联合中央区淋巴结清扫术.经过131I"清甲"治疗后中位随访26个月,将患者的临床转归根据美国甲状腺协会(American Thyroid Association,ATA)2015年发布的《成人甲状腺结节与分化型甲状腺癌诊治指南》分为:满意(excellent response,ER)、不确切(indeterminate response,IDR)、血清学反应欠佳(biochemical incomplete response,BIR)和影像学反应欠佳(structural incomplete response,SIR).计算不同淋巴结清扫数对应的累计ER率(以ERn表示,n为淋巴结清扫数,ERn为清扫数小于等于n枚淋巴结后达到ER的患者数占清扫数小于等于n枚淋巴结的总人数的百分比),分析中央区淋巴结清扫数与ERn的关系.结果:随着中央区淋巴结清扫数增多,ERn总体呈上升趋势,ER1、ER5、ER10和ER30分别为25.0%、66.7%、74.7%和79.1%,且n由1至10时ERn升高明显.n大于等于10的患者的满意率高于n小于10的患者,差异有统计学意义(85.7%vs 73.3%,P=0.05).多因素Logistic回归分析显示,中央区淋巴结清扫数大于等于10枚(OR=2.720,95%CI:1.052~7.033,P=0.039)、131I治疗前刺激性甲状腺球蛋白(stimulated thyroglobulin,sTg)水平(OR=0.955,95%CI:0.926~0.984,P=0.003)是影响ER的独立预后因素.结论:随着中央区淋巴结清扫数的增多,pN1a PTC患者131I"清甲"治疗后更易达到ER;对于淋巴结转移数小于等于5枚的pN1a PTC患者,中央区淋巴结清扫数大于等于10枚有助于其131I"清甲"治疗后达到ER.     

The number and ratio of positive lymph nodes are independent prognostic factors for patients with major salivary gland cancer: Results from the surveillance,epidemiology, and End Results dataset

IntroductionTo investigate whether the positive lymph node number (PLNN) and positive lymph node ratio (PLNR) could predict the prognosis of patients with major salivary gland cancer (MSGC) and to identify the optimal cutoff points for these variables that stratify patients according to their risk of survival.MethodsWe used the Surveillance, Epidemiology, and End Results (SEER) database to identify all patients with MSGC between 1988 and 2014. A logistic regression analysis was carried out to evaluate the risk factors for lymph node metastasis (LNM) in MSGC. The X-tile program was used to identify the cutoff values for the PLNN and PLNR in MSGC patients with LNM. Cox proportional hazards regression models were performed to identify the predictors of cancer-specific survival (CSS).ResultsIn the SEER database, 8668 eligible patients were identified and 3046 of them had LNM. The logistic regression analysis indicated that older age, male sex, larger tumor size, higher grade, tumor extension and high-risk pathology were associated with LNM. The X-tile program showed that a PLNN>4 and a PLNR>0.15 were prognostic indicators of CSS. A multivariable analysis indicated that, after the factors that might potentially affect the prognosis were adjusted for, the PLNN and PLNR were still associated with CSS.ConclusionsOur Results demonstrated that the PLNN and PLNR were independent prognostic indicators for MSGC patients with lymph node metastasis.     

Defining the incidence and clinical significance of lymph node metastasis in soft tissue sarcoma

Introduction

The incidence and clinical significance of lymph node metastasis (LNM, N1) in soft tissue sarcoma (STS) is unclear. Recent studies have focused on extremity/trunk STS (ETSTS). We sought to define the subgroup of patients with LNM at sarcoma diagnosis across all disease sites and histologies.

Dye- and gamma probe-guided sentinel lymph node biopsy in breast cancer patients: using patent blue dye and technetium-99m-labeled human serum albumin

BACKGROUND: Sentinel lymph node (SLN) biopsy is a promising method for the diagnosis of the axillary nodal status. We examined the availability of the SLN biopsy using two mapping procedures: the dye- and gamma probe-guided method, and preoperative lymphoscintigraphy by gamma camera imaging. METHODS: We enrolled 48 patients with breast cancer. Technetium-99m-labeled human serum albumin was injected into the subdermal tissue above the primary tumor or biopsy cavity, and preoperative gamma camera imaging was performed. After induction of general anesthesia, patent blue dye was injected into the peritumoral area prior to the surgical procedure. A handheld gamma-detection probe was used to assist in SLN detection. Careful dissection was performed to identify blue-stained afferent lymphatic vessels and nodes. An SLN was defined as any blue and/or radioactive node, and was excised. After SLN biopsy, axillary lymph node dissection of level I, II, and III was completed, in order to confirm the diagnostic ability of the SLN biopsy. RESULTS: Intraoperative SLN identification of axillary lesions was successful in 43 of 48 patients (90%). The dye- and gamma probe-guided method was successful in 25 patients (52%), the dye-guided method alone succeeded in 11 patients (23%), and the gamma probe-guided method alone succeeded in 7 patients (15%). Preoperative lymphoscintigraphy revealed axillary focal accumulations in 29 of 48 patients (60%). All patients who underwent successful preoperative SLN identification by lymphoscintigraphy had successful intraoperative SLN identification. A diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100% were achieved in the diagnosis of axillary metastasis. Internal mammary SLNs were identified in four patients intraoperatively, but we could not detect cancer metastasis in the internal mammary SLNs. CONCLUSIONS: The dye-guided and gamma probe-guided methods were complementary. Preoperative lymphoscintigraphy was useful to predict intraoperative SLN identification. Further study is necessary to assess the role of SLN biopsy of the internal mammary lymph nodes.     

Prognostic significance of microscopic and macroscopic extracapsular spread from metastatic tumor in the cervical lymph nodes

It has been established that the presence or absence of cervical node metastases in patients with head and neck squamous cell carcinoma (HNSCC) is a powerful prognostic indicator. This report reviews the evolution of thinking over the past 70 years with regard to the import and detection of cervical nodal metastases which exhibit spread of tumor beyond the confines of the original encompassing nodal capsule. In the process, this discussion touches upon clinical examination, gross and microscopic pathologic examination, and radiographic imaging studies. In particular, the distinction between gross nodal extracapsular spread of tumor and microscopic nodal extracapsular spread of tumor has been drawn in recent reports; this raises the possibility that identification of microscopic breaching of the node capsule by tumor might provide clinically significant information which is not provided by the gross observation of an intact lymph node capsule. While it remains to be seen whether microscopic extracapsular spread alone will prove to be an important prognostic factor, it is recommended that selective neck dissection continue to be offered even in those patients with clinically negative necks; further studies should aid in defining the import of microscopic extracapsular tumor spread in patients with positive cervical nodes.     

Molecular signatures of lymph node status by intrinsic subtype: gene expression analysis of primary breast tumors from patients with and without metastatic lymph nodes

Background

Identification of a gene expression signature in primary breast tumors that could classify patients by lymph node status would allow patients to avoid the morbidities of surgical disruption of the lymph nodes. Attempts to identify such a signature have, to date, been unsuccessful. Because breast tumor subtypes have unique molecular characteristics and different sites of metastasis, molecular signatures for lymph node involvement may vary by subtype.

Methods

Gene expression data was generated from HG U133A 2.0 arrays for 135 node positive and 210 node negative primary breast tumors. Intrinsic subtype was assigned using the BreastPRS. Differential gene expression analysis was performed using one-way ANOVA using lymph node status as the variable with a False-discovery rate <0.05, to define significance.

Results

Luminal A tumors were most common (51%) followed by basal-like (27%), HER2-enriched (14%) luminal B (7%) and normal-like (1%). Basal-like and luminal A tumors were less likely to have metastatic lymph nodes (35% and 37%, respectively) compared to luminal B or HER2-enriched (52% and 51%, respectively). No differentially expressed genes associated with lymph node status were detected when all tumors were considered together or within each subtype.

Conclusions

Gene expression patterns from the primary tumor are not able to stratify patients by lymph node status. Although the primary breast tumor may influence tumor cell dissemination, once metastatic cells enter the lymphatics, it is likely that characteristics of the lymph node microenvironment, such as establishment of a pre-metastatic niche and release of pro-survival factors, determine which cells are able to colonize. The inability to utilize molecular profiles from the primary tumor to determine lymph node status suggest that other avenues of investigation, such as how systemic factors including diminished immune response or genetic susceptibility contribute to metastasis, may be critical in the development of tools for non-surgical assessment of lymph node status with a corresponding reduction in downstream sequelae associated with disruption of the lymphatics.

     

TC-1在非小细胞肺癌的表达及与淋巴结转移的关系

目的：探讨TC-1蛋白在非小细胞肺癌（NSCLC）组织中的表达及其在病理分类、分级、TNM分期中的差异性,为进一步研究TC-1在NSCLC中的作用及其机制提供依据。方法：采用免疫组化EnVinsion法检测TC-1蛋白在95例非小细胞肺癌中的表达,统计学分析其在病理分类、分级及临床TNM分期及淋巴结转移与否的差异性。结果：免疫组化结果显示TC-1阳性表达主要位于胞浆中和部分胞核。肺鳞癌和腺癌总阳性率分别为63.46%、72.09%,差异性不显著（P=0.154）。鳞癌高、中、低分级阳性率分别为20.00%、65.51%、72.22%,经Kruskal-Wallis H检验无明显差异性（P=0.075）。腺癌的高、中、低分级的阳性率分别是33.33%、65.21%、88.23%,差异性非常显著（P=0.005）。NSCLC（鳞癌、腺癌）的TNM分期Ⅰa、Ⅰb、Ⅱa、Ⅱb、Ⅲa、Ⅲb的表达强度经检验差异性显著（P=0.029）。有淋巴结转移者原发灶阳性率为90.57%（48/53）、无淋巴结转移者原发灶阳性率为38.09%（16/42）,经Mann-Whitney U秩和检验差异性非常显著（P=0.000）。53例伴淋巴结转移的NSCLC原发灶与淋巴结转移灶阳性表达相关性用Spearman检验,有相关性（r=0.39,P=0.000）。结论：TC-1在非小细胞肺癌（NSCLC）组织中高表达,TC-1表达与病理分型、鳞癌分级无关,与腺癌分级、NSCLC TNM分期、淋巴结转移与否相关。提示TC-1在肺癌组织中表达高低与淋巴结转移密切相关。     

舌体鳞癌颈淋巴结转移的规律和治疗策略

背景与目的:目前,对临床颈淋巴结阴性(cN0)的舌癌病例是否需行颈淋巴清扫术治疗仍存争议。本研究目的在于探讨舌体鳞癌的颈部淋巴结转移规律和分区性颈淋巴结清扫术应用于cN0舌癌病例的理论依据和应用原则。方法:回顾性分析1991年至1997年214例手术治疗的舌体鳞癌患者的临床资料;分析cN0pN+(病理检查淋巴结阳性)病例和cN+pN+病例的颈部转移淋巴结分布规律;比较不同分组的远期疗效;Cox回归分析法筛选影响舌体鳞癌患者预后的因素。结果:pN+病例69例,颈淋巴结转移率32.2%,其中同侧Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ区各占22.3%、33.5%、22.3%、4.6%、1.0%;对侧Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ区各占6.6%、3.6%、3.0%、2.0%、0.5%。pN+组和pN0组5年生存率各为47%、83%(P<0.001);Cox回归分析显示影响舌体鳞癌患者预后的独立因素为T分期、N分期。结论:舌体鳞癌淋巴结转移最常见于同侧颈部Ⅰ、Ⅱ、Ⅲ区;分区性颈淋巴结清扫术对cN0病例既可起治疗的作用,又可用于评价颈部淋巴结转移状况以决定是否行全颈淋巴结清扫术。     

Initial metastatic, including micrometastatic, sites of lymph nodes in esophageal squamous cell carcinoma

BACKGROUND AND OBJECTIVES: It is important to identify the initial lymph node metastasis when performing less invasive surgery. The purpose of the present study was to analyze locations of solitary lymph node metastasis and micrometastasis in esophageal carcinoma. METHODS: We retrospectively analyzed the initial sites of lymph node metastasis in esophageal cancer. Sixty-five consecutive patients with solitary lymph node metastasis, and 33 pN0 patients with only lymph node micrometastasis detected by immunohistochemistry, were classified according to tumor location and tumor depth. RESULTS: The location of lymph node metastasis in the 22 patients with superficial cancer was limited to recurrent nerve nodes (RN) in the upper thoracic esophagus; RN, paraesophageal nodes (PE), or perigastric nodes (PG) in the middle or lower thoracic esophagus. Thirty-six patients with advanced cancer had lymph node metastasis at RN, PE, or PG locations, while in the remaining seven, lymph node metastasis was found in areas far from the primary tumor. Regarding the 33 patients with lymph node micrometastasis, the locations of micrometastasis were similar to those of solitary metastasis. CONCLUSIONS: Although less invasive surgery, such as reduction of lymphadenectomy, may be suitable for superficial cancer, it should be performed with special care in advanced cancer.     

TC-1在非小细胞肺癌的表达及与淋巴结转移的关系

目的:探讨TC-1蛋白在非小细胞肺癌(NSCLC)组织中的表达及其在病理分类、分级、TNM分期中的差异性,为进一步研究TC-1在NSCLC中的作用及其机制提供依据。方法:采用免疫组化EnVinsion法检测TC-1蛋白在95例非小细胞肺癌中的表达,统计学分析其在病理分类、分级及临床TNM分期及淋巴结转移与否的差异性。结果:免疫组化结果显示TC-1阳性表达主要位于胞浆中和部分胞核。肺鳞癌和腺癌总阳性率分别为63.46%、72.09%,差异性不显著(P=0.154)。鳞癌高、中、低分级阳性率分别为20.00%、65.51%、72.22%,经Kruskal-Wallis H检验无明显差异性(P=0.075)。腺癌的高、中、低分级的阳性率分别是33.33%、65.21%、88.23%,差异性非常显著(P=0.005)。NSCLC(鳞癌、腺癌)的TNM分期Ⅰa、Ⅰb、Ⅱa、Ⅱb、Ⅲa、Ⅲb的表达强度经检验差异性显著(P=0.029)。有淋巴结转移者原发灶阳性率为90.57%(48/53)、无淋巴结转移者原发灶阳性率为38.09%(16/42),经Mann-Whitney U秩和检验差异性非常显著(P=0.000)。53例伴淋巴结转移的NSCLC原发灶与淋巴结转移灶阳性表达相关性用Spearman检验,有相关性(r=0.39,P=0.000)。结论:TC-1在非小细胞肺癌(NSCLC)组织中高表达,TC-1表达与病理分型、鳞癌分级无关,与腺癌分级、NSCLC TNM分期、淋巴结转移与否相关。提示TC-1在肺癌组织中表达高低与淋巴结转移密切相关。     

甲状腺乳头状癌颈部淋巴结转移的处理态度和诊疗现状

甲状腺乳头状癌(Papillary thyroid carcinoma,PTC)虽以惰性居多,但颈部淋巴结转移的患者并不少见,而颈淋巴结转移的发生也意味着死亡率增加和复发风险的提高,甲状腺手术前应使用彩超充分评估颈部淋巴结的状态,对直径较大的淋巴结行超声引导下淋巴结细针抽吸(Echo-guided fine needle aspiration of the lymph node,LN-FNA)或联合测定洗脱液的甲状腺球蛋白水平,在怀疑远处转移或肿瘤浸润性生长时可联合CT、PET-CT或磁共振检查。建议临床医生在有技术保证的前提下对术中冰冻为阴性的cN0患者行单侧的预防性中央区淋巴结清扫术(Prophylactic central neck dissection,pCND),对术中冰冻为阳性的cN0患者行双侧的中央区淋巴结清扫术,在降低患者复发率的同时减少术后并发症的发生,应严格按照指南评估患者术后是否需行放射性碘治疗,以减少不必要的放射性治疗,更好地服务于患者,提升患者的生存质量。     

Prognostic significance of the ratio between metastatic and dissected lymph nodes (n ratio) in patients with advanced gastric cancer

BACKGROUND AND OBJECTIVES: To determine the prognostic significance of the ratio between metastatic and dissected lymph nodes (n ratio) in gastric cancer patients. METHODS: We retrospectively reviewed 777 advanced gastric cancer patients who had undergone curative gastrectomy at our hospital. RESULTS: The n ratio was significantly greater in cases with a large tumor, undifferentiated tumor, lymphatic vessel invasion, or blood vessel invasion. Furthermore, the n ratio was significantly correlated with the depth of invasion, level of lymph node metastasis, and number of lymph node metastases. The prognosis for gastric cancer patients correlated well with the n ratio. Multivariate analysis indicated that the n ratio, but not the number of lymph node metastases, was an independent prognostic indicator. Moreover, the n ratio was an independent prognostic factor in N1, N2, and N3 patients defined by the Japanese Classification of Gastric Cancer (JCGC). CONCLUSIONS: The n ratio is useful for evaluating the status of lymph node metastasis in gastric cancer. Therefore, the addition of the n ratio to the N (nodal) category defined by the JCGC may be a useful strategy in the N-staging classification of gastric cancer.     

早期胃癌淋巴结转移及临床意义

淋巴结转移是影响早期胃癌手术方式选择和预后的重要因素,对其转移规律和特点的认识及检测方法的掌握对于合理开展缩小手术至关重要。运用免疫组化和逆转录聚合酶链反应技术对早期胃癌前哨淋巴结检测不仅可以了解淋巴结站的转移特点、规律,而且可以发现微转移,从而指导术中淋巴结清扫范围而选择合理术式,避免标准根治术淋巴结清扫和扩大的手术方式对机体造成不必要的损害,减少手术创伤和术后并发症的出现,提高患者术后生存质量。     

重视甲状腺乳头状癌中胸锁乳突肌-胸骨舌骨肌间淋巴结的处理

目前关于甲状腺乳头状癌中胸锁乳突肌-胸骨舌骨肌间淋巴结（the lymph node between sternocleidomastoid and sternohyoid muscle,LNSS）转移的相关研究较少。文献报道,LNSS在初治甲状腺乳头状癌（papillary thyroid cancer,PTC）中的转移率为7.4%~23.5%,但因其解剖位置隐蔽而易在颈淋巴结清扫中被忽视。LNSS认知的加深对于术中充分暴露相关区域并予以彻底清扫具有十分重要的临床意义,现将针对LNSS概念的提出及目前临床研究现状进行总结,指出PTC患者颈部淋巴结处理中LNSS的重要性及必要性。