头颈部恶性肿瘤嗜神经侵袭临床诊治现状

嗜神经侵袭是肿瘤通过神经扩散与转移的一种独特的生物学行为,与复发、转移、预后密切相关。随着研究的不断深入,人们普遍认识到嗜神经侵袭的临床意义。但由于头颈部肿瘤发病率相对较低,不同解剖部位、不同病理类型嗜神经发生率各不相同,故缺乏高级别的循证医学证据。目前嗜神经侵袭的病理学机制尚未完全阐明,也无针对神经侵犯的特异性治疗手段,因此头颈部肿瘤嗜神经侵袭的治疗对于临床医师是一个巨大的挑战。本文就头颈部恶性肿瘤中嗜神经侵袭的临床诊治现状做一综述。     

肿瘤嗜神经侵袭机制的研究进展

肿瘤嗜神经侵袭（perineural invasion，PNI）被认为是一种新的恶性肿瘤转移方式，与多种肿瘤不良预后相关。神经与肿瘤细胞之间的相互作用主要包括细胞形态的改变和分子间作用。肿瘤微环境中的多种分子包括神经营养因子、趋化因子、黏附分子及神经递质等在肿瘤PNI形成过程中发挥重要作用。探究神经与肿瘤的相互作用，可为揭示肿瘤形成或转移的机制及优化临床诊疗提供帮助。     

肿瘤嗜神经侵袭和肿瘤微环境研究进展

肿瘤嗜神经侵袭易引起患者疼痛以及肿瘤的复发,越来越受到重视.肿瘤微环境与肿瘤嗜神经侵袭密切相关,微环境中有多种因子参与了肿瘤嗜神经侵袭,肿瘤嗜神经侵袭也会改变微环境.本文从二者的相互作用,作一综述.     

非神经源性恶性肿瘤嗜神经侵袭机制研究进展

部分非神经源性恶性肿瘤除具有浸润、复发及转移的一般特性外,还有一个较为特殊的临床表现就是嗜神经侵袭。肿瘤细胞嗜神经侵袭可能是多种因素参与、共同作用的复杂过程,而肿瘤细胞发生雪旺细胞分化、神经营养因子及其受体、神经细胞黏附分子则是该机制研究的热点。同时,整合素、细胞间黏附分子、ECM、MMP及TIMP等因素在肿瘤细胞侵袭神经的过程中所起的作用也不容忽视。随着肿瘤嗜神经侵袭机制研究工作的不断发展,我们对恶性肿瘤NI的分子机制将会有更多的认识。在与肿瘤细胞NI有关的因素中,便于检测的指标被筛选并运用到恶性肿瘤的临床诊治实践中,必将推动肿瘤临床诊治策略的进一步完善。     

GDNF和ARTN及其受体与消化系统肿瘤嗜神经侵袭的关系

肿瘤嗜神经侵袭(PNI)被认为是一种新的恶性肿瘤转移方式,也是某些肿瘤病人术后复发率高和预后差的重要原因之一。研究发现,神经胶质源性神经生长因子(GDNF)和ARTN的表达与某些肿瘤的侵袭呈正相关,能够促进肿瘤组织与其周围神经的相互移行,在肿瘤PNI的发展进程中起着非常重要的作用。本文综述了GDNF和ARTN及其受体在消化系统肿瘤PNI中的表达和作用机制,以期为消化系统肿瘤的临床治疗以及预后判断提供新的研究思路。     

APE/Ref-1和HIF-1α在头颈部肿瘤中表达的临床意义

APE／Ref-1和HIF—1α是与肿瘤的发生、进展、侵袭、转移及放射反应性密切相关的两个因子。本文从APE／Ref-1和HIF—1α的生物学特性、与头颈部肿瘤发生发展的关系以及与头颈部肿瘤放射反应性关系三方面概述APE／Ref-1和HIF—1α在头颈部肿瘤的诊断、临床分期、预后判断以及开展合理规范的个体化治疗的应用前景等方面的临床意义。     

RNA干扰技术抑制涎腺腺样囊性癌的研究进展

涎腺腺样囊性癌是头颈部常见的恶性肿瘤之一,具有早期易血行转移,嗜神经侵袭,术后易局部复发及远处转移等特点。目前,对丧失手术机会的患者尚缺乏有效的治疗手段。RNA干扰作为一种可高效、特异性沉默目的基因的手段已被广泛应用于各种肿瘤研究。通过利用RNA干扰技术沉默腺样囊性癌的癌基因、抗凋亡因子及黏附、迁移相关因子等基因的表达后,腺样囊性癌的发展受到了明显的抑制。本文拟对涎腺腺样囊性癌的RNA干扰治疗进展进行综述。     

Neuropilin-1在消化道恶性肿瘤发生发展中的生物学作用

消化道肿瘤是最常见的恶性肿瘤,发病率高,死亡率亦高。神经纤毛蛋白-1（Neuropilin-1）在消化道恶性肿瘤发生发展中的作用成为近年来研究的热点,其调控恶性肿瘤血管生成过程,介导肿瘤细胞的增殖与侵袭,从而促进肿瘤进展与转移。本文就Neuropilin-1在肿瘤血管生成、肿瘤增殖与侵袭、转移及肿瘤治疗靶标中的作用作一综述。     

肾上腺外嗜铬细胞瘤

伴有肾上腺素释放过多症状的高血压,应引起临床医生对肾上腺髓质瘤和肾上腺外嗜铬神经系统肿瘤的警惕。嗜铬神经分布广泛,包括肾上腺體质、化学感受器(颈动脉体和主动脉体)、迷走神经和少部分与颈、胸、腹部交感神经有关的神经细胞。功能性的嗜铬神经肿瘤又叫功能性嗜铬神经瘤或肾上腺外嗜铬细胞瘤。泌尿外科医生必须熟悉本病的诊断、定位和处理。嗜铬神经系统的胚胎学基础嗜铬神经实质细胞伴随其他自主神经细胞来源于神经脊,分布于:①动脉和头颈部的颈神经节附近;②颈、胸、腹和盆腔的交感神经     

鼻咽癌侵袭与转移相关基因的研究进展

0引言鼻咽癌是头颈部常见恶性肿瘤之一,其局部复发及远处转移一直是影响鼻咽癌患者长期存活的主要因素。而肿瘤的侵袭与转移是受多种因素调控的复杂过程,涉及肿瘤细胞增殖、肿瘤新血管形成、肿瘤细胞黏附、细胞凋亡以及肿瘤细胞迁移运动等一     

Expression of neural cell adhesion molecule in salivary adenoid cystic carcinoma and its correlation with perineural invasion

The expression of neural cell adhesion molecule (NCAM) was analyzed in immunohistochemical preparations from adenoid cystic carcinoma. The goal was to evaluate whether NCAM expression could be used as a biological marker for the perineural invasion of adenoid cystic carcinoma in the head and neck. The presence of perineural invasion and NCAM expression was evaluated in samples from 49 patients. Perineural invasion was identified in 33 of them (67%). A high incidence of perineural invasion was found in adenoid cystic carcinoma in the parotid, hard palate, maxillary sinus and oral cavity. Positive NCAM staining was observed in 28 of 49 patients (57%). Of the 28 patients with NCAM staining, perineural invasion was identified in 24 (86%). In contrast, only 9 (43%) of the 21 tumors without NCAM staining had perineural invasion. The difference in NCAM expression between cases with and without perineural invasion was statistically significant (p<0.01). When positive NCAM staining was used to estimate the presence of perineural invasion, the sensitivity was 73 and the specificity 75%. Histopathologic nodal involvement was found in 6 of 18 cases in which neck dissection had been performed. All 6 cases displayed positive NCAM staining, and 5 displayed perineural invasion in the primary adenoid cystic carcinoma. In conclusion, NCAM expression can, to a certain extent, be used as a predictor of perineural invasion in adenoid cystic carcinoma. Moreover, lymph node metastases could serve as a clinical indicator for perineural invasion and for NCAM expression.     

High-risk non-melanoma skin cancer of the head and neck

High-risk non-melanoma skin cancer (NMSC) of the head and neck is difficult to manage, given its propensity for regional metastasis, perineural invasion, direct parotid invasion, and bony destruction. Management of these tumors demands awareness of the characteristics contributing to their recurrence. Recent studies emphasize the importance of treatment of the parotid gland and cervical lymph nodes to improve locoregional control. A multidisciplinary approach to the assessment and treatment of high-risk NMSC is required to provide comprehensive care. This review also covers recent advances in the understanding of NMSC biology and new approaches in chemoprevention.     

Facial nerve palsy as a result of squamous cell carcinoma of the skin

Perineural invasion is increasingly recognized as a significant mode of tumor spread in squamous cell carcinoma (SCC) of the skin. Clinically, it is very difficult to diagnose perineural involvement in the majority of patients due to the lack of symptoms. The occasional propensity for perineural invasion from SCCs of the skin of the head and neck region is well documented and, although SCCs arising from actinically damaged skin reportedly have a low incidence of metastasis or deep invasion, failure to recognize this potential mode of spread could result in fatal consequences.     

Perineural Invasion of Head and Neck Skin Cancer: Diagnostic and Therapeutic Implications

Perineural invasion of head and neck skin cancer is a poorly understood and often misdiagnosed pathological entity. Incidental or microscopic perineural invasion is identified by the pathologist and often leads to confusion as to how the patient should be further treated. The less common but more aggressive clinical perineural spread presents with a clinical deficit, which is too commonly misinterpreted by the clinician. This review will try to clarify the terminology that exists in the literature and explore the mechanisms of invasion and spread. It will look at the recent advances in diagnosis and comment on the limitations inherent in current classification schemes. A review of outcomes will be included and current treatment strategies utilized discussed.     

ACR appropriateness criteria® adjuvant therapy for resected squamous cell carcinoma of the head and neck

Locoregional recurrence following surgical resection alone for stage III/IV head and neck cancer is common. Adjuvant radiotherapy has been shown to improve post-operative locoregional control when compared to pre-operative radiotherapy for head and neck cancers. Following surgical resection, adverse pathological features determine the need for adjuvant therapy. High-risk pathologic features include extranodal tumor spread and involved surgical margins. Other adverse pathologic features include T 3-4 tumors, perineural invasion, lymphovascular space invasion, low neck adenopathy, and multiple tumor involved cervical lymph nodes. The standard adjuvant therapies are post-operative radiation therapy or post-operative chemoradiotherapy. Post-operative chemoradiotherapy yields superior locoregional control, progression-free survival, and in some studies, overall survival compared to post-operative radiotherapy for high-risk patients in multiple randomized studies. Pooled analyses of randomized data demonstrate that post-operative concurrent chemoradiotherapy is associated with overall survival benefits for patients with involved surgical margins as well as those with extranodal tumor spread. Post-operative radiotherapy concurrent with cisplatin at 100 mg/m(2) every 21 days is the current standard chemoradiotherapy platform adjuvant head and neck cancer treatment. Post-operative radiotherapy and post-operative chemoradiotherapy radiation treatment volumes are not standardized and should be designed based on the risk of recurrence and clinically occult involvement of head and neck subsites and nodal regions. Evidence supports a post-operative radiotherapy and chemoradiotherapy radiation dose of at least 63 Gy for high-risk patients and at least 57 Gy for low risk patients.     

The Value of Periodic Follow-up in the Detection of Recurrences after Radical Treatment in Locally Advanced Head and Neck Cancer

AimsTo determine the value of routine follow-up in detecting and salvaging recurrence after radical treatment of locally advanced head and neck squamous cell carcinoma and to identify clinical or pathological prognostic factors that predicted for survival.Materials and methodsA retrospective medical chart review was conducted at the Odette Cancer Centre between January 2000 and May 2006. Two hundred and twenty-three patients with advanced (stage III or IV) squamous cell carcinoma of the head and neck who were treated with curative intent were reviewed. Recurrences were divided into local, regional or distant recurrences. The detection method for each recurrence was categorised as self or physician detected. A self-detected recurrence arose from symptoms that led to investigations that confirmed a recurrence (even if initiated at the time of a routine visit), whereas a physician-detected recurrence was found during the routine follow-up examination and was asymptomatic.ResultsThere was no evidence to suggest a significant improvement in disease-free or overall survival in the physician-detected versus patient-detected groups. Regional and distant recurrences were only detected by physicians in one-fifth of cases and, overall, patients self-detected their own recurrence in two-thirds of the cases that experienced disease progression within the sample. Of the 12 clinical/pathological variables considered, only the response to treatment and perineural invasion were associated with survival.ConclusionsCurrent surveillance methods do not appear to improve cancer control in the stage III/IV head and neck squamous cell carcinoma population. However, technological advances and biomarker development may lead to surveillance technique enhancements. Also, post-treatment follow-up remains important for the evaluation of treatment results, emotional support and management of late complications. Among the clinical and pathological factors considered, only the treatment response and perineural invasion predicted survival.     

Perineural spread of basal cell carcinomas treated with Mohs micrographic surgery

BACKGROUND: Perineural spread is a well-documented feature of cutaneous tumors and may portend a more aggressive course. The incidence of perineural invasion in basal cell carcinoma (BCC) is reportedly 1%. The authors sought to determine whether perineural spread occurs more commonly than previously thought. METHODS: The authors prospectively evaluated 434 patients with BCC treated with Mohs surgery, assessing the presence or absence of perineural inflammation and invasion in tumors requiring more than one stage of surgery. They also documented the demographic features, clinical characteristics, histologic subtype, and operative data in each case. RESULTS: Seventy-eight BCCs required more than one stage of Mohs surgery. Perineural inflammation, perineural tumor invasion, or both were present in 29 of the 78 tumors (37%), or 6.7% of all 434 prospectively evaluated cases. Twenty-one of the 78 tumors (26.9%) exhibited perineural inflammation, 3 (3.8%) demonstrated perineural invasion, and 5 (6.4%) exhibited both. Tumors with perineural invasion required 5.3 surgical stages on average for clearance, in contrast to tumors without perineural invasion, which required 2.2 stages. Tumors with perineural inflammation, inflammation plus tumor invasion, and invasion alone were, respectively, 138%, 149%, and 194% greater in area preoperatively than tumors without perineural involvement, and their mean defect areas after Mohs surgery were, respectively, 151%, 121%, and 605% larger than those of tumors without perineural involvement. CONCLUSIONS: The incidence of perineural invasion among cases of BCC appears higher than previously recognized. Tumor aggressiveness appears to correlate with the presence of perineural invasion. Surgery with horizontal frozen-section margin control enables easy detection of perineural involvement and should therefore be strongly considered for the treatment of high risk BCC patients.     

Skin cancer of the head and neck with perineural invasion

Perineural invasion occurs in 2% to 6% of cutaneous basal and squamous cell carcinomas of the head and neck and is associated with midface location, recurrent tumors, high histologic grade, and increasing tumor size. Patients may be asymptomatic with perineural invasion appreciated on pathologic examination of the surgical specimen (incidental) or may present with cranial nerve deficits (clinical). The cranial nerves most commonly involved are the 5th and 7th nerves. Magnetic resonance imaging is obtained to detect and define the extent of perineural invasion; computed tomography is used to detect regional lymph node metastases. Patients with apparently resectable cancers undergo surgery usually followed by postoperative radiotherapy. Patients with incompletely resectable cancers are treated with definitive radiotherapy. The 5-year local control, cause-specific survival, and overall survival rates are approximately 87%, 65%, and 50%, respectively, for patients with incidental perineural invasion compared with 55%, 59%, and 55%, respectively, for those with clinical perineural invasion.     

Small cell carcinoma of the head and neck: a review

Small cell carcinoma (SCC) has become recognized as a distinct, though relatively infrequent, clinical pathology that occurs in multiple sites throughout the head and neck. Excluding cases that are considered to arise from skin, SCC in the head and neck has been found to develop in nearly all structures associated with the upper aerodigestive tract. Among the head and neck sites, the frequency of SCC is greatest in the larynx, with salivary glands and the sinonasal region comprising the other principle areas of origin. Controversy exist as to whether SCC can develop as a distinct entity in the thyroid, with most tumors that previously would have been considered as SCC now found to be lymphomas or variant forms of other types of thyroid malignancy. While there seems to be some differences among tumors arising from the various subsites, in general all SCC that originate in the head and neck have a tendency for aggressive local invasion and a strong propensity for both regional and distant metastasis. Treatment may include surgical resection, radiotherapy, chemotherapy, or some combination of these modalities. Due to the infrequency of these tumors, it is very unlikely that any large, controlled study will ever be done. For this reason, recommendations for treatment of SCC arising in the head and neck are based primarily on retrospective data from various small case series and on comparative data for treatment of SCC of bronchogenic and other extrapulmonary origin. Although patients with truly limited local disease may enjoy some prolonged survival, most patients with this tumor do poorly despite all current attempts at treatment.