头颈部鳞癌颈淋巴结隐匿性转移

目的探讨头颈部鳞癌隐匿性颈淋巴结转移的特点和规律。方法对111例头颈部鳞癌N0M0患者的颈淋巴结清扫标本进行切片观察。结果隐匿性转移总体发生率为26．12％(29／111)。其中口腔癌18．75％(15／80)，口咽癌25．00％(1／4)，下咽癌54．54％(6／11)，喉癌43．75％(7／16)。原发癌临床分期、肿瘤细胞分化程度是影响颈淋巴结隐匿性转移的重要因素。111例N0M0患者5年生存率为66．7％，其中pN^-为74．39％(61／82)，pN^ 为44．82％(13／29)。结论对临床T3和T4期、癌组织分化程度低和深度浸润的cN0头颈部鳞癌应行选择性颈清扫术以治疗颈淋巴结隐匿性转移并提高患者的生存率。     

头颈部鳞癌颈部转移淋巴结的评估

头颈部鳞癌的重要生物学特性之一是淋巴转移。而转移淋巴结的临床诊断却一直困扰着耳鼻咽喉头颈外科医生，本文对临床应用ＣＴ、ＭＲＩ等高科技手段对其诊断情况及不同部位原发肿瘤颈部治疗对策进行综述。     

头颈部鳞癌颈淋巴结转移方式的临床病理学研究

为了探讨头颈肿瘤颈淋巴结转移的规律，对３８４侧根治性颈淋巴清扫标本进行连续切片观察。发现颈淋巴结转移病理阳性的总发生率为６０．４％，其中Ｎ０病例颈淋巴结转移率为３１．７％，Ｎ１～３颈转移率为８１．２％；口腔癌主要向Ⅰ、Ⅱ和Ⅲ区转移，口咽癌、下咽癌和喉癌主要向Ⅱ、Ⅲ和Ⅳ区转移。转移的淋巴结主要分布于一个或相邻的三个解剖区。颈淋巴结转移病理阳性和淋巴结包膜破坏的发生率随着临床Ｎ分期的增加而升高，且后者在Ｎ２，３中的发生率明显高于Ｎ０，１。提示对Ｎ０，１的病例可行区域选择性颈清扫并追加术后放疗。对Ｎ２，３的病例应行根治性颈清扫术，以彻底清除转移灶并改善患者预后。     

头颈部鳞癌颈淋巴结隐匿性转移

目的 探讨头颈部鳞癌隐匿性颈淋巴结转移的特点和规律。方法 对111例头颈部鳞癌N_0M_0患者的颈淋巴结清扫标本进行切片观察。结果 隐匿性转移总体发生率为26.12％(29/111)。其中口腔癌18.75％(15/80),口咽癌25.00％(1/4),下咽癌54.54％(6/11),喉癌43.75％(7/16)。原发癌临床分期、肿瘤细胞分化程度是影响颈淋巴结隐匿性转移的重要因素。111例N_0M_0患者5年生存率为66.7％,其中pN~-为74.39％(61/82),pN~ 为44.82％(13/29)。结论 对临床T_3和T_4期、癌组织分化程度低和深度浸润的cN_0头颈部鳞癌应行选择性颈清扫术以治疗颈淋巴结隐匿性转移并提高患者的生存率。     

头颈鳞癌血管生成与颈淋巴结转移相关性研究

目的 :探讨头颈鳞癌血管生成与其颈淋巴结转移的关系以及血管内皮生长因子(VEGF)在头颈鳞癌血管生成中的作用。方法 :应用免疫组化SABC法检测 5 8例头颈鳞癌组织中微血管密度 (IMVD)及VEGF的表达。结果 :5 8例头颈鳞癌组织中IMVD为 2 3.93± 8.77,肿瘤分化程度 ,高与中、高与低间 ,IMVD差异有显著性意义 (均P <0 .0 5 ) ;中与低间 ,差异无显著性意义 (P >0 .0 5 )。颈淋巴结转移组IMVD(2 7.92± 9.11)明显高于非转移组 (2 0 .6 9± 7.0 8) ,其差异有显著性意义 (P <0 .0 1)。癌组织中VEGF表达与瘤内IMVD呈正相关 (rs=0 .4 87,P <0 .0 1)。结论 :瘤内IMVD可作为预测头颈鳞癌颈淋巴结转移的一个重要指标 ;VEGF可促进头颈鳞癌血管生成。     

头颈部鳞癌颈淋巴结转移方式的临床病理学研究

为了探讨头颈肿瘤颈淋巴结转移的规律，对３８４侧根治性颈淋巴清扫标本进行连续切片观察，发现颈淋巴结转移病理阳性的总发生率为６０．４％，其中Ｎ０病例颈淋巴结转移率为３１．７％，Ｎ１－３颈转移率为８１．２％，口腔癌主要向Ⅰ，Ⅱ和Ⅲ区转移，口咽癌，下咽癌和喉癌主要向Ⅱ，Ⅲ和Ⅳ区转移，转移的淋巴结主要分布于一个或相邻的三个解剖区。颈淋巴结转移病理阳性和淋巴结包膜破坏的发生率随着临床Ｎ分期的增加而升高，且后者     

下咽癌颈淋巴结转移区域探讨

目的研究下咽癌颈淋巴结转移区域的特点及术后治疗策略。方法回顾性分析2004年7月～2008年7月于我科住院治疗的18例下咽癌患者的临床资料,18例患者均行手术治疗,术前未行放疗或化疗,将术中肿瘤原发灶及根治性颈廓清术中的颈淋巴结标本按区域标记逐一进行病理观察,确定肿瘤原发部位及颈淋巴结转移区域。术后随访3～5年,观察淋巴转移与患者的关系。结果 18例下咽癌颈淋巴结转移率为88.9%（16/18）;颈淋巴结转移的主要区域为LevelⅡ区、LevelⅢ区,转移率分别为73.1%、69.2%;其次为LevelⅣ区8.3%,未发现LevelⅠ区、LevelⅤ及LevelⅥ区淋巴结转移。结论下咽癌颈淋巴结转移率较高,转移区域同侧为主,以LevelⅡ、LevelⅢ区常见。颈淋巴结位置的下移和转移淋巴结的直径与患者的预后呈正相关。     

下咽癌颈淋巴结转移区域探讨

目的 研究下咽癌颈淋巴结转移区域的特点及术后治疗策略,改善预后.方法 回顾性分析2002年7月～2008年7月于我科住院治疗的35例下咽癌患者的临床资料,29例患者均行手术治疗,且术前未行放疗或化疗,将术中肿瘤原发灶及颈清扫术中的颈淋巴结标本按区域标记逐一进行病理观察,确定肿瘤原发部位及颈淋巴结转移区域.通过随访3～5年,观察转移及预后.结果 29例下咽癌总的颈淋巴结转移率为86.2％(25/29),颈淋巴结转移的主要区域为Level Ⅱ区、Level Ⅲ区,转移率为73.8％、69.0％,其次为Level Ⅳ区7.7％,未发现Level Ⅰ区、Level Ⅴ及LevelⅥ区淋巴结转移.结论 下咽癌颈淋巴结转移率较高,转移区域同侧为主,以Level Ⅱ、Level Ⅲ区常见.随着颈淋巴结位置的下移及转移淋巴结直径的增大,患者的预后越来越差.     

Soft tissue cervical metastases of squamous carcinoma of the head and neck

Some 497 of 3085 patients with squamous cell carcinoma of the head and neck treated between 1963 and 1990 had a later radical neck dissection at some time after initial treatment. The histological slides were all reviewed, firstly to confirm the presence of squamous cell carcinoma within the neck, and secondly to ascertain whether the metastasis was to soft tissue, to a lymph node or to both. The presence of extracapsular rupture in lymph node deposits was also assessed. Of the 497 patients, 138 had soft tissue deposits only, and 359 had nodal deposits only. Of the patients with nodal deposits 165 had extracapsular rupture and 194 did not. The 5-year survival of the 138 patients with soft tissue metastases was 27% compared with 33% for patients with extracapsular rupture and 50% for patients with no extracapsular rupture. Weighted logistic regression showed that soft tissue deposits were significantly more common in patients in poor general condition, plus poorly differentiated squamous cell carcinoma plus T₄ tumours (P < 0.005), and in patients with poorly differentiated squamous cell carcinoma plus T₄ tumours (P < 0.025). Cox's multivariate analysis with backward elimination showed that gender, histological differentiation, site of primary tumour and age of patient had no statistically significant effect on survival. The number of nodes (P < 0.0001), the presence of extracapsular rupture (P < 0.0001) and the presence of soft tissue free metastases (P < 0.001) were all highly significant. The N-status at recurrence also reached statistical significance (P < 0.0001).     

Sentinel lymph node biopsy in head and neck squamous cell carcinoma

OBJECTIVES/HYPOTHESIS: Sentinel lymph node biopsy is a minimally invasive method to stage the regional lymphatics that has revolutionized the management of patients with intermediate-thickness cutaneous melanoma. Head and neck surgeons have been encouraged by the accuracy of sentinel lymph node biopsy in cutaneous melanoma and have applied the technique to patients with head and neck squamous cell carcinoma (HNSCC). The objectives of the study were 1) to study the feasibility and accuracy of sentinel lymph node biopsy as a method to stage the regional lymphatics in HNSCC and 2) to determine whether there are qualitative differences between the cutaneous and mucosal lymphatics that would affect the technique used in HNSCC. STUDY DESIGN: Two methods of investigation were employed: a prospective laboratory study using a feline model for sentinel lymph node biopsy and a retrospective review of patients who received lymphoscintigraphy before neck dissection and intraoperative identification of the sentinel lymph node. METHODS: Lymphoscintigraphy and a gamma probe were used in four felines to study the kinetics of technetium-labeled sulfa colloid (Tc-SC) in the mucosal lymphatics. In the second part of the feline study, eight subjects were studied intraoperatively. Tc-SC and isosulfan blue dye were used to study the injection technique for the mucosal lymphatics and to determine the time course of the dye and Tc-SC to the sentinel lymph node. In Part II of the present study, a retrospective review of 33 patients with HNSCC was conducted. Twenty patients (stage N0) whose treatment included elective neck dissection were studied with preoperative lymphoscintigraphy and underwent intraoperative identification of the sentinel lymph node to determine the accuracy and feasibility of sentinel lymph node biopsy. Eight patients with palpable neck disease and five patients with recurrent or second primary disease whose previous treatment included neck dissection were also studied with lymphoscintigraphy before neck dissection. RESULTS: In the feline study, both Tc-SC and isosulfan blue dye traversed the lymphatics rapidly, appearing in the sentinel lymph node in less than 5 minutes. Modification of the injection technique used for cutaneous melanoma was required to depict the sentinel lymph node of the base of tongue. In the human study, the sentinel lymph node was accurately identified in 19 of 20 (95%) N0 patients. On average, 2.9 sentinel lymph nodes (range, 1-5) were identified in 2.2 (range, 1-4) levels of the neck. Sentinel lymph nodes were bilateral in 4 of 19 patients. When the sentinel lymph node was identified, it accurately predicted the pathological nodal status of the regional lymphatics. Three of 20 patients had cervical metastases, and the sentinel lymph node was identified in 2 of 3 patients with pathologic nodes (pN+). Focal areas of radiotracer uptake were identified in seven of eight patients with palpable disease. These areas corresponded to the level with palpable disease in four patients. The lymphatics delineated by lymphoscintigraphy in the five patients with previous neck dissection were outside the levels that had been dissected. Lymphoscintigraphy depicted collateral patterns of lymphatic drainage. CONCLUSIONS: Sentinel lymph node biopsy is technically feasible and is a promising, minimally invasive method for staging the regional lymphatics in patients with stage N0 HNSCC. Lymphoscintigraphy alone may determine the levels that require treatment in patients with disrupted or previously operated cervical lymphatics.     

Patterns of bone metastases from head and neck squamous cell carcinoma

ObjectiveTo report clinical features of bone metastases (BM) from head and neck squamous cell carcinoma (HNSCC).MethodsAmong 772 patients with HNSCC diagnosed at our hospital over 9 years, 30 patients (3.9%) had clinical evidence of BM (24 men and 6 women; mean age: 63 years). We assessed the time interval from the primary diagnosis to BM development, symptoms attributable to BM, presence of distant metastases to other organs, number of BM, sites of BM, morphologic changes on computed tomography (CT) images, treatment for BM, and overall survival (OS).ResultsBM at the initial stage were found in 9 patients with HNSCC (30%), and in 21 patients (70%) with HNSCC during the course of the disease. In the later patients, the median time interval from the primary diagnosis was 11.5 months. Nineteen patients (63%) did not have BM-related symptoms, 6 (20%) had pain, 3 (10%) had neurologic symptoms resulting from vertebral or skull metastases, and 2 (7%) had hypercalcemia. Seventeen patients (57%) showed bone-exclusive metastases, and 13 (43%) had distant metastases in other organs. Eleven patients (37%) had monostotic metastases (solitary BM), and 19 patients (63%) had polyostotic metastases (multiple BM). When combined, 9 patients (30%) showed bone-exclusive and monostotic metastases. The most commonly affected site was the thoracolumbar spine, accounting for 34% of total BM, followed by the pelvis (24%), shoulder and thorax (21%), and the extremities (17%). Notably, metastases to bones above the clavicle (craniofacial bones and cervical spine) accounted for only 3% of all bone lesions. CT images showed variable morphologic patterns with osteolytic type in 17 patients (57%), intertrabecular in 7 (23%), osteoblastic in 4 (13%), and mixed in 2 (7%). Systematic chemotherapy for BM was performed in 19 patients and radiotherapy in 18. The median survival time for patients with bone-exclusive and monostotic metastases was significantly longer than that for patients with multi-organ metastases or polyostotic metastases at 18.2 months vs. 5.7 months (p = 0.02). Neither chemotherapy nor radiotherapy extended OS.ConclusionThirty percent of BM cases from HNSCC showed bone-exclusive and monostotic metastases. These patients tended to show a more favorable prognosis than patients with multi-organ metastases or polyostotic metastases.     

Detection of occult cervical micrometastases in patients with head and neck squamous cell cancer

OBJECTIVE: The incidence of occult nodal metastases associated with head and neck squamous cell carcinoma (HNSCC) and the clinical significance of nodal micrometastases by cytokeratin immunohistochemical analysis are examined. STUDY DESIGN: In all, 1012 lymph nodes from 50 patients treated between 1992 and 2001 at the University of Colorado Health Sciences Center (Denver, CO) were evaluated retrospectively for micrometastases. METHODS: Serial sectioning in 5-to 6-microm interval specimens stained either with hematoxylin and eosin (H&E) or immunostaining for cytokeratins using the monoclonal antibody cocktail AE1/AE3 was performed in 21 N0, 11 N1, and 14 N2 patient cases. Cases that showed scattered cells with suspect staining qualities but without morphological features consistent with HNSCC were further evaluated by epithelial membrane antigen (EMA) immunohistochemical analysis. RESULTS: H&E-stained and cytokeratin-stained sections revealed occult nodal micrometastases in 3.8% of N0 and 5% of N1 cases. Overall, 26 micrometastases were identified in N0 and N1 patients, causing 29% of N0 patients and 45% of N1 patients to be upstaged. Cytokeratin immunostaining detected micrometastases in eight cases that were negative on H&E serial sectioning. Serial sectioning by H&E alone identified three additional micrometastases. Negative EMA immunostaining confirmed the absence of malignant cells in lymph node sections that were equivocal on cytokeratin staining. CONCLUSIONS: The use of serial sectioning with H&E and cytokeratin immunohistochemical analysis increases the detection of micrometastases that are often elusive by routine processing in patients with HNSCC. Improved methods of detecting micrometastases may provide a basis for improved planning of postoperative therapy for patients already at risk for tumor recurrence.     

前哨淋巴结检测在头颈部鳞状细胞癌中的应用

目的　评价前哨淋巴结 (sentinellymphnode ,SLN)检测在N0头颈鳞状细胞癌 (简称鳞癌 )中的可行性以及SLN对微小转移灶的诊断价值。方法　分析研究中国医学科学院肿瘤医院头颈外科 2 0 0 1年 8月～ 2 0 0 2年 2月收治的 10例头颈鳞癌患者 ,为未经治疗临床诊断为N0的患者。所有患者术前均在肿瘤周围的黏膜下注射锝标记的右旋糖酐胶体 (technetium 99m preparedwithdextrancolloid ,99mTc DX) ,约 30min后行单光子发射计算机断层显像术扫描 ,在相应的颈部皮肤上标记显像“热点” ;术中翻开皮瓣后用手提探测仪探测术野 ,以高于背景计数 4倍以上确定为SLN。将确定的SLN送病理学检查 ,并借助淋巴结连续切片和免疫组化法检测微小转移灶。结果　术前淋巴结显像及术中探测仪探测所识别的SLN行病理学检查 ,10例N0患者有 3例发现隐性转移 ,其隐性转移率为 30 % (3/ 10 ) ,SLN的阳性率为 2 2 .7% (5 / 2 2 ) ,非SLN的阳性率为 0 .4 % (1/ 2 4 7)。经病理证实为SLN阴性的患者的非SLN无阳性发现。结论　头颈鳞癌颈部N0的SLN检测对发现临床隐性转移灶是可行的。SLN检测技术可缩小手术范围 ,减少手术的创伤及并发症 ,该技术的进一步推广还需更多的研究。     

Lymph node ratio as a prognostic factor for survival in patients with head and neck squamous cell carcinoma

Objective

The purpose of this study is to validate the concept of lymph node ratio (LNR) in head and neck squamous cell carcinoma (HNSCC).

CD73 expression in lymph node metastases in patients with head and neck cancer

Introduction: CD73 is an enzyme crucial in the metabolism of immunosuppressive adenosine. In cancer, it has various functions including tumor growth and metastases. Squamous cell carcinoma of the head and neck has an overall poor prognosis, also due to early spread of metastatic cells.

Materials and methods: Tumor and lymph node specimens of 65 patients with HNSCC were subjected to immunohistochemical and H-score analysis of CD73 expression. Demographics, diagnoses, histopathology and subsequent outcome were analyzed.

Results: The primary cancer was squamous cell carcinoma in all patients (male/female 55:10) with the following locations: oral cavity n:16, oropharynx n:28, hypopharynx n:11 and larynx n:10. H-score for CD73 expression in the primary lesion and metastatic lymph nodes was significantly higher in advanced compared to early stages with no significant differences among tumor locations. High CD73 expression was associated with reduced overall survival rates at a mean follow-up of 83.4 months (6–204 months).

Conclusions: CD73 expression in HNSCC correlated positively with tumor stage and was associated with poor prognosis. Therefore, CD73 expression in primary lesions and regional metastases appears to predict HNSCC patients at high risk of all tumor sites. Therapeutic approaches targeting CD73 might seem promising for this patient population.     

头颈部鳞状细胞癌的靶向治疗研究进展

头颈部肿瘤是常见肿瘤之一,超过95%的病理类型是鳞状细胞癌,手术与放化疗结合的综合治疗方案是头颈部鳞状细胞癌(HNSCC)的主要治疗方案,但是总体生存率并不高,主要原因是肿瘤复发和/或转移;同时复发性或转移性HNSCC常无法进行手术治疗,放化疗效果也差。靶向治疗的发现为HNSCC、特别是复发性或转移性HNSCC的治疗提供了新的方法。为了进一步认识靶向治疗的临床治疗作用,就HNSCC的靶向治疗研究进展做一综述。     

Foxp3 expression in lymph node metastases in patients with head and neck cancer

Introduction: The prevalence and activity of regulatory T cells in patients with cancer correlates with poor prognosis. These cells are characterized by their expression of Forkhead box protein-3 (Foxp3). Squamous cell carcinoma is the most prevalent type of cancer in the head and neck region with overall poor survival rates, also due to early spread of metastatic cells.

Material and methods: Primary tumor specimens as well as lymph node specimens harvested during neck dissection of 65 patients with a diagnosis of HNSCC were subjected to immunohistochemical and H-score analysis of Foxp3 expression. Demographics, diagnoses, histopathology and subsequent outcome were analyzed.

Results: The primary cancer was squamous cell carcinoma in all patients (male/female 55:10) with the following tumor locations: oral cavity n?=?16, oropharynx n?=?28, hypopharynx n?=?11 and larynx n?=?10 (Stage III n?=?18; Stage IVA n?=?45; Stage IVB n?=?2). The H-score for Foxp3 expression in the primary lesion as well as metastatic lymph nodes was significantly higher in advanced stages compared to early stages with differences among tumor locations, which were not significant. High Foxp3 expression was associated with inferior overall survival rates at a mean follow-up of 83.4 months (6–204 months)

Conclusions: Foxp3 expression in HNSCC varied from the anatomical site and correlated positively with tumor stage and was associated with poor prognosis. Therefore, Foxp3 expressions in primary lesions as well as lymphogenic metastases appear to predict high-risk HSNCC patients. Novel therapeutic approaches targeting Foxp3⁺ cells might seem promising for this patient population.