2024_06_20_d067c9192569944f57e5g

Surgical tumour margins and their significance in oral squamous cell carcinoma
手术肿瘤边缘及其在口腔鳞状细胞癌中的意义

Department of Oral and Maxillofacial Surgery, Queen Alexandra Hospital, Portsmouth, UK

英国朴茨茅斯亚历山德拉皇后医院口腔颌面外科

Graduate Program in Oral Biology, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil

巴西圣保罗皮拉西卡巴坎皮纳斯大学牙科学院口腔生物学研究生课程

Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil

坎皮纳斯大学牙科学院口腔诊断系，巴西圣保罗皮拉西卡巴

Department of Head and Neck Oncology, Centre for Academic Research, HCG Cancer Center, Bengaluru, Karnataka, India

印度卡纳塔克邦班加罗尔HCG癌症中心学术研究中心头颈肿瘤科

Department of Oral and Maxillofacial Surgery, Navodaya Dental College and Hospital, Raichur, Karnataka, India

印度卡纳塔克邦 Raichur 的 Navodaya 牙科学院和医院口腔颌面外科

Correspondence 通信

Peter A. Brennan, Department of Oral and Maxillofacial Surgery, Queen Alexandra Hospital, Portsmouth, UK.
Peter A. Brennan，英国朴茨茅斯亚历山德拉皇后医院口腔颌面外科。

Email: Peter.brennan@porthosp.nhs.uk
电子邮件： Peter.brennan@porthosp.nhs.uk

Abstract 抽象

There are many prognostic indicators used to predict tumour recurrence and overall prognosis in oral squamous cell carcinoma (OSCC). Most of these biological factors cannot be directly influenced by clinicians managing these heterogeneous group of tumours. Excision margins can potentially be increased at the time of surgery by including more normal tissue than the commonly accepted resection distance from the macroscopic tumour edge. However, this can lead to poorer quality of life for patients and does not necessarily address microscopic extensions or dicohesive patterns of tumour growth. Surgical margins can be affected by tissue shrinkage immediately following resection and the choice of instrument used for surgery. Currently, most regard a clear resection margin as being , a close margin as more than but and an involved margin . In this article, we provide a brief overview of tumour margins in OSCC, including several recently published large meta-analyses. Based upon these and other studies, there is still conflicting data in the literature about the ideal margin for OSCC. There is a growing body of evidence that suggests a clearance of might be adequate for some cancers. However, adequacy of resection should be considered along with the many other prognostic indicators of OSCC when the multi-disciplinary team considers further treatment for these patients.
有许多预后指标用于预测口腔鳞状细胞癌（OSCC）的肿瘤复发和总体预后。这些生物学因素中的大多数不能直接受到管理这些异质性肿瘤组的临床医生的影响。在手术时，通过包括比普遍接受的与宏观肿瘤边缘的切除距离更多的正常组织，切除边缘可能会增加。然而，这可能导致患者的生活质量下降，并不一定能解决肿瘤生长的微观延伸或二面模式。手术切缘可能会受到切除后立即组织萎缩和手术器械选择的影响。目前，大多数人认为清晰的切除切缘是，紧密切缘是大于但，而累及的切缘。在本文中，我们简要概述了 OSCC 的肿瘤边缘，包括最近发表的几项大型荟萃分析。基于这些研究和其他研究，文献中关于OSCC理想利润率的数据仍然存在相互矛盾。越来越多的证据表明，清除某些癌症可能就足够了。然而，当多学科团队考虑对这些患者进行进一步治疗时，应将切除的充分性与OSCC的许多其他预后指标一起考虑。

KEYWORDS 关键字

oral squamous cell carcinoma, prognosis, surgical margin
口腔鳞状细胞癌、预后、手术切缘

1 | INTRODUCTION 1 |介绍

In oral squamous cell carcinoma (OSCC), several well-known histopathological parameters, including patterns of invasion, tumour thickness, perineural and lympho-vascular invasion (PNI and LVI) and inflammatory response, have been described as prognostic indicators. More recently, tumour budding and tumour-stroma ratio (TSR) have also been included.

Many of these prognostic factors represent markers of tumour biology and behaviour and are therefore outside the surgeons' control during ablative surgery. However, one factor that (to an extent) can be influenced by surgical practice is the excised margin. Increasing surgical margins by removing more normal looking tissue is one option, but the more the tissue that is removed, the larger the surgical defect requiring reconstruction. This can potentially further compromise the patient's quality of life.

Increasingly, there is a move towards more tissue sparing surgery, while not compromising surgical resections. This is even more apparent in the larynx where robotic surgery is being used to excise tumours while preserving as much functional tissue as possible. An unexpected positive margin is often not due to surgical technique
在口腔鳞状细胞癌（OSCC）中，几个众所周知的组织病理学参数，包括侵袭模式、肿瘤厚度、神经周围和淋巴血管浸润（PNI 和 LVI）以及炎症反应，已被描述为预后指标。最近，肿瘤出芽和肿瘤-基质比（TSR）也被包括在内。

这些预后因素中有许多是肿瘤生物学和行为的标志物，因此在消融手术期间不受外科医生的控制。然而，（在一定程度上）可能受外科手术影响的一个因素是切除的边缘。通过切除更多看起来正常的组织来增加手术切缘是一种选择，但切除的组织越多，需要重建的手术缺损就越大。这可能会进一步损害患者的生活质量。

越来越多的人倾向于在不影响手术切除的同时进行更多的组织保留手术。这在喉部更为明显，机器人手术被用来切除肿瘤，同时保留尽可能多的功能组织。意外的阳性切缘通常不是由于手术技术造成的
but occurs as a result of discohesive tumour growth and microscopic extension beyond the macroscopic tumour margin. Most surgeons will include a

margin of surrounding normal looking tissue to give the best chance of a clear margin, while also not removing too much normal tissue.
但由于盘状肿瘤生长和微观肿瘤边缘超出宏观肿瘤边缘而发生。大多数外科医生会在周围正常组织

的边缘，以提供清晰边缘的最佳机会，同时也不会去除太多的正常组织。

2 | CLEAR VS. CLOSE OR INVOLVED MARGINS
2 |清除 VS.接近或涉及的保证金

Achieving clear margins is the main objective in the surgical management of OSCC as this is associated with reduced risk of recurrence and improved survival.

In contrast, an involved margin or one with inadequate adjacent normal tissue (a close margin) has negative prognostic implications and in such cases further resection or adjuvant treatment is often required.

There have been several recent systematic reviews and meta-analysis of tumour margin status and prognosis.

As might be expected, improvement in oncological outcomes improves as the surgical margin progresses from involved to close to clear.

What is clearly apparent in all these large studies is that an involved margin necessitates the need for adjuvant treatment to reduce the likelihood of tumour recurrence at the primary site or more distant disease.
实现清晰的切缘是 OSCC 手术治疗的主要目标，因为这与降低复发风险和提高生存率有关。

相反，受累边缘或邻近正常组织不足（边缘较近）的缘对预后有负面影响，在这种情况下，通常需要进一步切除或辅助治疗。

最近有几篇关于肿瘤边缘状态和预后的系统评价和荟萃分析。

正如预期的那样，随着手术切缘从受累到接近清晰的进展，肿瘤学结局的改善会得到改善。

在所有这些大型研究中，显而易见的是，受累边缘需要辅助治疗，以减少原发部位肿瘤复发或更远疾病复发的可能性。

A recent meta-analysis, the largest of its kind to date, has found a strong association between the positive tumour margin and the risk of overall survival (OS), disease-specific survival (DSS) and recurrence.

eligible studies with pooled analyses of surgical margins were considered. These included 63470 patients ( 31 studies), with OS data, 20680 patients

with DSS data and 15300 patients (25 articles) with data for disease-free survival (DFS).
最近的一项荟萃分析是迄今为止同类分析中规模最大的，发现阳性肿瘤边缘与总生存期（OS）、疾病特异性生存期（DSS）和复发风险之间存在密切关联。

考虑了对手术切缘进行汇总分析的合格研究。这些包括63470名患者（31项研究），有OS数据，20680名

患者有DSS数据，15300名患者（25篇文章）有无病生存期（DFS）数据。

The distance used in millimetres to define a clear surgical margin was variable, but most studies used a

or more of normal tissue from the tumour edge. A recent survey of American Surgeons found that most respondents thought that

more was required for a specimen to be reported as having a clear cancer margin.

用于定义清晰手术边缘的距离（以毫米为单位）是可变的，但大多数研究使用

肿瘤边缘的一个或多个正常组织。最近对美国外科医生进行的一项调查发现，大多数受访者认为，要报告标本具有明显的癌症边缘，需要

更多。

Most published studies have compared clear margins (

of normal tissue) against a combination of close (

of normal tissue) and involved (

of normal tissue) margins. In the recent large meta-analysis,

studies did not define the margin distance but instead grouped tumour resections as those with either clear margins or close/involved margins. Pooled analyses confirmed that one or more involved resection margins were significantly associated with worse OS, DSS and DFS, irrespective of the amount of normal tissue from the tumour edge in the rest of the specimen.

大多数已发表的研究将清晰边缘（

正常组织）与紧密（

正常组织）和受累（

正常组织）边缘的组合进行了比较。在最近的大型荟萃分析中，

研究没有定义切缘距离，而是将肿瘤切除分为切除边缘清晰或边缘紧密/受累的切除术。汇总分析证实，无论标本其余部分肿瘤边缘的正常组织数量如何，一个或多个受累切除边缘与较差的 OS、DSS 和 DFS 显着相关。

3 | EFFECTS OF SPECIMEN SHRINKAGE ON EXCISION MARGIN
3 |试样收缩对切除边缘的影响

Despite marking a clinical

margin from the edge of the macroscopic tumour, there will be shrinkage of the specimen following resection. This is often most apparent in floor of mouth and ventral tongue cancers where the soft tissue margin can reduce
尽管在宏观肿瘤的边缘标记了临床

边缘，但切除后标本会收缩。这通常在口底癌和腹侧舌癌中最为明显，在这些癌症中，软组织边缘可以缩小

FIGURE 1 Use of a harmonic scalpel to resect a T2 lateral tongue squamous cell carcinoma. After initially marking the excision margins with a monopolar diathermy, the harmonic gives an almost bloodless surgical field
图 1 使用谐波手术刀切除 T2 外侧舌鳞状细胞癌。在最初用单极透热疗法标记切除边缘后，谐波给出几乎不流血的手术区域

upon specimen removal. Various published studies have found that immediately after resection overall specimen shrinkage can exceed

, a property primarily due to the intrinsic tissue characteristics.

As hard tissues bone and cartilage are not affected by this process. Further shrinkage can occur during fixation in formalin, although some have reported this as being less significant that what occurs following tumour excision.

An area which is sometimes overlooked is the surgical method used for resection. A study in pigs found that standard monopolar cutting diathermy and coagulation diathermy both caused significant thermal damage to the resected tissue with denaturing of the underlying muscle.

These methods of excision are widely used by surgeons. Laser excision was not investigated, but it is known that this also causes more thermal damage than using a harmonic scalpel, which operates at around

. In contrast to standard diathermy, less injury and tissue contraction were found when either a Harmonic scalpel or conventional scalpel was used.

The former is a surgical instrument used which simultaneously cuts and cauterizes tissue. In the harmonic scalpel, high frequency ultrasonic energy of approximately

is converted to mechanical energy at the active blade which vibrates longitudinally against an inactive blade over an excursion of

. The vibration disrupts hydrogen bonds in water within the tissue at a relatively lower temperature than conventional diathermy. Furthermore, an advantage of the harmonic scalpel is that bleeding is almost eliminated completely
取出标本后。各种已发表的研究发现，切除后立即整体标本收缩可以超过

，这一特性主要是由于内在组织特征。

由于硬组织、骨骼和软骨不受此过程的影响。在福尔马林固定期间可能会发生进一步的收缩，尽管有些人报告说这不如肿瘤切除后发生的情况那么重要。

一个有时被忽视的领域是用于切除的手术方法。一项针对猪的研究发现，标准的单极切割透热疗法和凝血透热疗法都会对切除的组织造成严重的热损伤，并导致下层肌肉变性。

这些切除方法被外科医生广泛使用。没有研究激光切除，但众所周知，这也比使用谐波手术刀造成更多的热损伤，谐波手术刀在

.与标准透热疗法相比，使用谐波手术刀或传统手术刀时，损伤和组织收缩更少。

前者是一种同时切割和烧灼组织的手术器械。在谐波手术刀中，大约

的高频超声波能量在有源刀片处转换为机械能，该机械能在偏移期间

对非活动刀片纵向振动。振动会破坏组织内水中的氢键，温度比传统透热疗法低。此外，谐波手术刀的一个优点是几乎完全消除了出血
making for a much cleaner and precise resection (Figure 1). It is easily able to seal the

lingual artery during tongue resections. For these reasons, and for at least the last 5 years, our practice is almost exclusively to use the harmonic scalpel for intra-oral resections.
使切除更干净、更精确（图1）。在舌头切除术期间，它很容易密封

舌动脉。由于这些原因，至少在过去 5 年中，我们的做法几乎完全是使用谐波手术刀进行口内切除术。

We recently audited 112 oral cancer resections, performed over a 3-year period. The specimens comprised 91 soft tissue (tongue

patients) and 16 bone resections, with a clinical margin of

marked before excision.

of cases (90/112) were excised, with a histological excision margin of

(16/112) had a margin of more than

but

and

(5/112) had at least one positive margin (

). All patients were discussed at the head and neck cancer multi-disciplinary team (MDT) meeting, and for patients with involved margins, all had further treatment. Our approach has been to consider close margins at the MDT, in the context of other adverse prognostic features including primary tumour depth of invasion, extra nodal extension and the presence of PNI and/or LVI. If a margin of

is accepted as being adequate, our own series of 112 oral cancer resections has a

complete excision rate.
我们最近审核了 112 例口腔癌切除术，历时 3 年。标本包括 91 例软组织（舌

患者）和 16 例骨切除术，切除前的临床边缘为

标记。

的病例（90/112）被切除，组织学切除边缘为

（16/112）的边缘大

于 but

和

（5/112）至少有一个阳性边缘（

）。所有患者在头颈癌多学科团队（MDT）会议上进行了讨论，对于边缘受累的患者，所有患者都接受了进一步治疗。我们的方法是考虑 MDT 的近距离切缘，以及其他不良预后特征，包括原发性肿瘤浸润深度、额外的淋巴结延伸以及 PNI 和/或 LVI 的存在。如果一个边缘

被认为是足够的，我们自己的 112 个口腔癌切除系列具有

完全切除率。

4 | THE CONTINUING CONTROVERSY OF CLOSE SURGICAL MARGINS
4 |手术切缘紧密的持续争议

Despite large studies and meta-analyses, many of which have been included here, there is still controversy about the implications of the close surgical margin. The proximity of an excision margin is dependent on many factors including both tumour biology and operator expertise. A large recent study of 699 patients with clinically early OSCC found that only resection margins of

independently affected survival outcomes.

Another large study of 432 patients has questioned the commonly used

cut-off for close margins. Invasive tumour found within

of the specimen margin was associated higher local recurrence rate, though no significant difference was identified for margins with greater distances.

Others have found that each millimetre increase in excised margin provided a 3.67 months survival advantage from

Given the increasing evidence that margins of greater than

might be adequate for predicting outcomes, particularly in small tumours,

this could influence both surgical resection and outcome data. In our own recent oral cancer excision audit, an adequate margin of

would change the 'complete excision' rate from

to over

.
尽管进行了大量研究和荟萃分析，其中许多已纳入本文，但关于手术切缘紧密的影响仍然存在争议。切缘的接近程度取决于许多因素，包括肿瘤生物学和操作者的专业知识。最近一项针对 699 例临床早期 OSCC 患者的大型研究发现，只有

独立切缘会影响生存结局。

另一项针对 432 名患者的大型研究质疑了常用

的紧密切缘临界值。在

标本边缘内发现的浸润性肿瘤与较高的局部复发率相关，尽管对于距离较远的边缘没有发现显着差异。

其他人发现，切除切缘每增加一毫米，就有 3.67 个月的生存优势

，

鉴于越来越多的证据表明，切缘大于

可能足以预测结果，尤其是在小肿瘤中，

这可能会影响手术切除和结果数据。在我们自己最近的口腔癌切除审计中，足够的余量

将“完全切除”率从

更改为超过

。

Most of the evidence surrounding the 'adequacy' of surgical margins relates to that gained from analysis of soft tissue (mucocal) specimens which have been fixed and analysed following soft tissue shrinkage as discussed above. For oral SCC involving bone, in the UK, at least

bony margins (guided by staging radiology and intraoperative appearance) are included, even though tissue shrinkage is not an issue.

However, in our experience, surgical resection margins

are often indicated simply to allow optimal bony reconstruction with free-tissue transfer and patient-specific implants. Regardless, there is currently a paucity of evidence in the literature relating specifically to what defines adequate surgical bony margins in oral SCC. Medullary invasion appears to be a negative prognostic factor (constituting what is described as 'true' bony invasion) whereas cortical erosion alone does not.

围绕手术切缘“充分性”的大多数证据都与从软组织（粘液）标本分析中获得的证据有关，这些标本在软组织萎缩后被固定和分析，如上所述。对于累及骨骼的口腔鳞状细胞癌，在英国，即使组织萎缩不是问题，也至少

包括骨缘（根据放射学分期和术中表现指导）。

然而，根据我们的经验，手术切除切缘

通常只是为了通过游离组织移植和患者特异性植入物实现最佳骨重建。无论如何，目前文献中缺乏专门关于口腔鳞状细胞癌手术骨缘的定义的证据。髓质浸润似乎是一个负面的预后因素（构成所谓的“真正的”骨浸润），而皮质侵蚀本身则不是。

5 | ADJUNCTS TO INTRAOPERATIVE ASSESSMENT OF EXCISION MARGINS
5 |术中切缘评估的辅助手段

The use of intraoperative frozen section has failed to elicit a diseasefree or overall survival benefit in patients being treated for oral SCC.

A recent systematic review of frozen section (FS) and other intraoperative adjuncts for the assessment of surgical excision margins suggests that this evidence is based upon the more traditional (and increasingly historical) technique of defect-driven sampling for FS. The uptake of tumour specimen-driven FS (where the pathologist him/herself takes samples from the margins of the main tumour specimen) has been associated with a three times greater intraoperative detection of positive margins when compared with defect-driven FS.

Considering the importance of obtaining negative surgical margins on overall and DSS, specimen-driven FS warrants ongoing consideration in the management of oral SCC. Mohs micrographic assessment has been used by one group for oral SCC with a reduction in 5 -year local recurrence rate in their institution.

However, the technique is limited by the suitability of the specimen to be placed on a pathology slide in the necessary manner (for example, precluded by certain anatomical changes in the soft tissue or the presence of bone in the specimen). Furthermore, the process of serial margin assessment might considerably prolong the duration of surgery. Therefore, a significant amount of evidence is required to demonstrate its suitability and feasibility in surgery for oral SCC. Other approaches that are gathering an increasing evidence base include molecular analysis of tumour margins (detecting genetic markers to determine the risk of tumour recurrence in surrounding areas of field-cancerization), wide-field analysis (using fluorescent/nonfluorescent dye or autofluorscent imaging) and narrow-field analysis (using elastic-scattering/Raman spectroscopy, optical coherence tomography, confocal microscopy and high-resolution microendoscopy), all of which have been building an evidence base within the last decade.

术中冰冻切片的使用未能为接受口服鳞状细胞癌治疗的患者带来无病或总生存获益。

最近对冷冻切片（FS）和其他术中辅助药物评估手术切除切缘的系统评价表明，该证据基于更传统（且越来越具有历史意义）的缺陷驱动取样技术。与缺陷驱动的 FS 相比，肿瘤标本驱动的 FS（病理学家自己从主要肿瘤标本的边缘采集样本）的摄取与术中阳性边缘的检出率高出三倍相关。

考虑到在整体和 DSS 上获得阴性手术切缘的重要性，在口腔鳞状细胞癌的管理中需要持续考虑标本驱动的 FS。一组患者已使用莫氏显微影像学评估治疗口腔鳞状细胞癌，其机构的 5 年局部复发率降低。

然而，该技术受到标本以必要方式放置在病理载玻片上的适用性的限制（例如，由于软组织中的某些解剖学变化或标本中存在骨骼而排除）。此外，连续切缘评估的过程可能会大大延长手术时间。因此，需要大量证据来证明其在口腔鳞状细胞癌手术中的适用性和可行性。其他正在收集越来越多的证据基础的方法包括肿瘤边缘的分子分析（检测遗传标记以确定周围区域癌变区域肿瘤复发的风险）、宽场分析（使用荧光/非荧光染料或自发荧光成像）和窄场分析（使用弹性散射/拉曼光谱、光学相干断层扫描、共聚焦显微镜和高分辨率显微内窥镜），所有这些都在建立过去十年的证据基础。

6 | CONCLUSION 6 |结论

A positive margin following oral SCC excision is associated with a poorer prognosis but should always be considered in relation to other pathological indicators of aggressive disease. The actual margin of reported normal soft tissue around a completely excised cancer can be influenced by site, the instrumentation used for surgical excision and formalin fixation. There is increasing evidence to suggest that a 'close margin' which currently is taken to be

clearance from the tumour edge, may be appropriate and curative for some oral SCC, but further research is needed in this regard.
口服鳞状细胞癌切除术后切缘阳性与较差的预后相关，但应始终考虑与侵袭性疾病的其他病理指标相关的情况。完全切除的癌症周围报告的正常软组织的实际边缘可能受到部位、用于手术切除和福尔马林固定的器械的影响。越来越多的证据表明，目前被认为是从肿瘤边缘

清除的“紧密切缘”对于某些口腔鳞状细胞癌可能是合适且可治愈的，但在这方面需要进一步研究。

CONFLICT OF INTEREST 利益冲突

None. 没有。

DATA AVAILABILITY STATEMENT
数据可用性声明

The audit data included in this paper is available from the corresponding author upon request.
本文中包含的审计数据可应要求向通讯作者索取。

REFERENCES 引用

Almangush A, Pirinen M, Heikkinen I, Mäkitie AA, Salo T, Leivo I. Tumour budding in oral squamous cell carcinoma: a meta-analysis. Br J Cancer. 2018;118:577-586.
Almangush A， Pirinen M， Heikkinen I， Mäkitie AA， Salo T， Leivo I. 口腔鳞状细胞癌中的肿瘤萌芽：荟萃分析。Br J 癌症。2018;118:577-586.
Dourado MR, Miwa KYM, Hamada GB, et al. Prognostication for oral squamous cell carcinoma patients based on the tumour-stroma ratio and tumour budding. Histopathol. 2020;76:906-918.
Dourado MR、Miwa KYM、Hamada GB 等。口腔鳞状细胞癌患者基于肿瘤-基质比和肿瘤出芽的预后。组织蛋白。2020;76:906-918.
Mäkitie AA, Almangush A, Rodrigo JP, Ferlito A, Leivo I. Hallmarks of cancer: tumor budding as a sign of invasion and metastasis in head and neck cancer. Head Neck. 2019;41:3712-3718.
Mäkitie AA， Almangush A， Rodrigo JP， Ferlito A， Leivo I. 癌症的标志：肿瘤萌芽是头颈癌侵袭和转移的标志。头颈。2019;41:3712-3718.
Jimenez JE, Nilsen ML, Gooding WE, et al. Surgical factors associated with patient-reported quality of life outcomes after free flap reconstruction of the oral cavity. Oral Oncol. 2021;123:105574.
Jimenez JE、Nilsen ML、Gooding WE 等。与患者报告的口腔游离皮瓣重建后生活质量结果相关的手术因素。口服肿瘤。2021;123:105574.
Lin MC, Leu YS, Chiang CJ, et al. Adequate surgical margins for oral cancer: a Taiwan cancer registry national database analysis. Oral Oncol. 2021;119:105358.
Lin MC， Leu YS， Chiang CJ， et al.口腔癌的充分手术切缘：台湾癌症登记处国家数据库分析。口服肿瘤。2021;119:105358.
Mitchell DA, Kanatas A, Murphy C, et al. Margins and survival in oral cancer. Br J Oral Maxillofac Surg. 2018;56:820-829.
Mitchell DA、Kanatas A、Murphy C 等人。口腔癌的边缘和生存率。Br J 口腔颌面外科杂志 2018;56：820-829。
Hamman J, Howe CL, Borgstrom M, Baker A, Wang SJ, Bearelly S. Impact of close margins in head and neck mucosal squamous cell carcinoma: a systematic review. Laryngoscope. 2022;132:307-321. doi:10.1002/lary. 29690
Hamman J， Howe CL， Borgstrom M， Baker A， Wang SJ， Bearelly S. 头颈部粘膜鳞状细胞癌边缘的影响：系统评价。喉镜。2022;132:307-321.doi：10.1002/lary.29690
Bulbul MG, Tarabichi O, Sethi RK, Parikh AS, Varvares MA. Does clearance of positive margins improve local control in oral cavity cancer? A meta-analysis. Otolaryngol Head Neck Surg. 2019;161:235-244.
Bulbul MG、Tarabichi O、Sethi RK、Parikh AS、Varvares MA。清除阳性切缘是否能改善口腔癌的局部控制？荟萃分析。耳鼻喉头颈外科 2019;161：235-244.
Anderson CR, Sisson K, Moncrieff M. A meta-analysis of margin size and local recurrence in oral squamous cell carcinoma. Oral Oncol. 2015;51:464-469.
安德森 CR、西森 K、蒙克里夫 M.口腔鳞状细胞癌切缘大小和局部复发的荟萃分析。口服肿瘤。2015;51:464-469.
Dolens E, Dourado MR, Amlangush A, et al. The impact of histopathological features on the prognosis of oral squamous cell carcinoma: a comprehensive review and meta-analysis. Front Oncol 2021;11. doi:10.3389/fonc.2021.784924
Dolens E、Dourado MR、Amlangush A 等人。组织病理学特征对口腔鳞状细胞癌预后的影响：综合评价和荟萃分析。前线肿瘤 2021;11。doi：10.3389/fonc.2021.784924
Bulbul MG, Zenga J, Tarabichi O, et al. Margin practices in oral cavity cancer resections: Survey of American Head and Neck SOCIETY Members. Laryngoscope. 2021;131:782-787.
Bulbul MG、Zenga J、Tarabichi O 等人。口腔癌切除术的边缘实践：美国头颈部协会成员调查。喉镜。2021;131:782-787.
Umstattd LA, Mills JC, Critchlow WA, Renner GJ, Zitsch RP 3rd. Shrinkage in oral squamous cell carcinoma: an analysis of tumor and margin measurements in vivo, post-resection, and post-formalin fixation. Am J Otolaryngol. 2017;38:660-662.
Umstattd LA、Mills JC、Critchlow WA、Renner GJ、Zitsch RP 第 3 名。口腔鳞状细胞癌的缩小：体内、切除后和福尔马林固定后肿瘤和切缘测量的分析。我是 J Otolaryngol。2017;38:660-662.
Pangare TB, Waknis PP, Bawane SS, Patil MN, Wadhera S, Patowary PB. Effect of formalin fixation on surgical margins in patients with oral squamous cell carcinoma. J Oral Maxillofac Surg. 2017;75:1293-1298
Pangare TB、Waknis PP、Bawane SS、Patil MN、Wadhera S、Patowary PB。福尔马林固定对口腔鳞状细胞癌患者手术切缘的影响。口腔颌面外科杂志 2017;75:1293-1298
George KS, Hyde NC, Wilson P, Smith GI. Does the method of resection affect the margins of tumours in the oral cavity? Prospective controlled study in pigs. Br J Oral Maxillofac Surg. 2013;51:600-603.
乔治 KS、海德 NC、威尔逊 P、史密斯 GI。切除方法会影响口腔肿瘤的边缘吗？猪的前瞻性对照研究。Br J 口腔颌面外科杂志 2013;51：600-603。
Bajwa MS, Houghton D, Java K, et al. The relevance of surgical margins in clinically early oral squamous cell carcinoma. Oral Oncol. 2020;110:104913
Bajwa MS、Houghton D、Java K 等人。手术切缘在临床早期口腔鳞状细胞癌中的相关性。口服肿瘤。2020;110:104913
Tasche KK, Buchakjian MR, Pagedar NA, Sperry SM. Definition of "close margin" in oral cancer surgery and association of margin distance with local recurrence rate. JAMA Otolaryngol Head Neck Surg. 2017;143:1166-1172.
Tasche KK， Buchakjian MR， Pagedar NA， Sperry SM. 口腔癌手术中“近距离切缘”的定义以及切缘距离与局部复发率的关联。美国医学会耳鼻喉头颈外科杂志 2017;143：1166-1172。
Singh A, Mishra A, Singhvi H, et al. Optimum surgical margins in squamous cell carcinoma of the oral tongue: is the current definition adequate? Oral Oncol. 2020;111:104938.
Singh A、Mishra A、Singhvi H 等人。口腔舌鳞状细胞癌的最佳手术切缘：目前的定义是否充分？口服肿瘤。2020;111:104938.
Kerawala C, Roques T, Jeannon JP, Bisase B. Oral cavity and lip cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol. 2016;130(S2):S83-S89.
Kerawala C， Roques T， Jeannon JP， Bisase B. 口腔和唇癌：英国国家多学科指南。J Laryngol Otol.2016 年;130（S2）：S83-S89.
Fried D, Mullins B, Weissler M, et al. Prognostic significance of bone invasion for oral cavity squamous cell carcinoma considered T1/T2 by American Joint Committee on cancer size criteria. Head Neck. 2014;36:776-781.
Fried D、Mullins B、Weissler M 等人。骨浸润对口腔鳞状细胞癌的预后意义美国联合委员会癌症大小标准认为 T1/T2。头颈。2014;36:776-781.
Lubek JE, Magliocca KR. Evaluation of the bone margin in oral squamous cell carcinoma. Oral Maxillofac Surg Clin North Am. 2017;29:281-292.
Lubek JE， Magliocca KR. 口腔鳞状细胞癌骨缘的评估。口腔颌面外科临床北美 2017;29：281-292。
Mair M, Nair D, Nair S, et al. Intraoperative gross examination vs frozen section for achievement of adequate margin in oral cancer surgery. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;123:544-549.
Mair M、Nair D、Nair S 等人。术中大体检查与冰冻切片在口腔癌手术中实现足够的切缘。口腔外科口腔医学口腔病理醇口腔放射剂。2017;123:544-549.
Kain JJ, Birkeland AC, Udayakumar N, et al. Surgical margins in oral cavity squamous cell carcinoma: Current practices and future directions. Laryngoscope. 2020;130:128-138.
Kain JJ、Birkeland AC、Udayakumar N 等人。口腔鳞状细胞癌的手术切缘：当前实践和未来方向。喉镜。2020;130:128-138.
Bergeron M, Gauthier P, Audet N. Decreasing loco-regional recurrence for oral cavity cancer with total Mohs margins technique. J Otolaryngol Head Neck Surg. 2016;45:63.
Bergeron M， Gauthier P， Audet N. 使用全莫氏边缘技术减少口腔癌的局部区域复发。耳喉头颈外科杂志 2016;45：63。

How to cite this article: Brennan PA, Dylgjeri F, Coletta RD, Arakeri G, Goodson AM. Surgical tumour margins and their significance in oral squamous cell carcinoma. J Oral Pathol Med. 2022;51:311-314. doi:10.1111/jop.13276
如何引用本文： Brennan PA， Dylgjeri F， Coletta RD， Arakeri G， Goodson AM.手术肿瘤边缘及其在口腔鳞状细胞癌中的意义。口腔病理医学杂志 2022;51：311-314。doi：10.1111/jop.13276

Surgical tumour margins and their significance in oral squamous cell carcinoma 手术肿瘤边缘及其在口腔鳞状细胞癌中的意义