Novel insights on oral squamous cell carcinoma management using long non-coding RNAs

Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer biomarkers are a relatively advanced concept,and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies.This review underlines the function of long non-coding RNAs(lncRNAs)in the OSCC and its subsequent clinical implications.LncRNAs,a class of non-coding RNAs,are larger than 200 nucleotides and resemble mRNA in numerous ways.However,unlike mRNA,lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA,RNA,proteins,or microRNAs depending on concentration and localization in cells.Upregulation of oncogenic lncRNAs and downregulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers.Targeted inhibition of candidate oncogenic lncRNAs or overexpression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models.The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity.This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival,proliferation,invasion,migration,metastasis,angiogenesis,metabolism,epigenetic modification,tumor immune microenvironment,and drug resistance.Subsequently,we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems,providing details on ongoing research and outlining potential future directions for advancements in this field.In essence,this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.

A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma

Oral squamous cell carcinoma （OSCC） has a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral cavity that freely communicate across the midline, and it can facilitate the spread of neoplastic cells to any area of the neck consequently. Clinical and histopathologic factors continue to provide predictive information to contralateral neck metastases （CLNM） in OSCC, which determine prophylactic and adjuvant treatments for an individual patient. This review describes the predictive value of clinical-histopathologic factors, which relate to primary tumor and cervical lymph nodes, and surgical dissection and adjuvant treatments. In addition, the indications for elective contralateral neck dissection and adjuvant radiotherapy （aRT） and strategies for follow-up are offered, which is strongly focused by clinicians to prevent later CLNM and poor prognosis subsequently.

Neck observation versus elective neck dissection in management of clinical T1/2N0 oral squamous cell carcinoma: a retrospective study of 232 patients

Objective: The management of early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC) remains a controversial issue. The aim of this study was to compare the clinical outcomes of neck observation (OBS) and elective neck dissection (END) in treating patients with cT1/2N0 OSCC. Methods: A total of 232 patients with cT1/2N0 OSCC were included in this retrospective study. Of these patients, 181 were treated with END and 51 with OBS. The survival curves of 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates were plotted using the Kaplan-Meier method for each group, and compared using the Log-rank test. Results: There was no significant difference in 5-year OS and DSS rates between END and OBS groups (OS: 89.0% vs. 88.2%, P=0.906; DSS: 92.3% vs. 92.2%, P=0.998). However, the END group had a higher 5-year RFS rate than the OBS group (90.1% vs. 76.5%, P=0.009). Patients with occult metastases in OBS group (7/51) had similar 5-year OS rate (57.1% vs. 64.1%, P=0.839) and DSS rate (71.4% vs. 74.4%, P=0.982) to those in END group (39/181). In the regional recurrence patients, the 5-year OS rate (57.1% vs. 11.1%, P=0.011) and DSS rate (71.4% vs. 22.2%, P=0.022) in OBS group (7/51) were higher than those in END group (9/181). Conclusions: The results indicated that OBS policy could obtain the same 5-year OS and DSS as END. Under close follow-up, OBS policy may be an available treatment option for patients with clinical T1/2N0 OSCC.

Squamous cell carcinoma of the oral cavity and circulating tumour cells

Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.

An Analysis of the Potential Benefits of Metformin on Disease Recurrence in Oral and Oropharyngeal Squamous Cell Carcinoma

Objective: Diabetes mellitus type 2 has been associated with increased cancer risk and cancer related mortality. Metformin, one of the most widely used anti-diabetic medications, has been found to have important anticancer properties in addition to hypoglycemic effects. The effects of metformin on clinical outcomes in oral cavity (OC) and oropharyngeal (OP) squamous cell carcinoma (SCC) have not been thoroughly analyzed. The purpose of this study was to evaluate the effects of metformin use on cancer recurrence in diabetic patients with oral cavity and oropharyngeal squamous cell carcinoma. Design: Retrospective review. Setting: Academic tertiary medical center. Patients: Seventy-seven patients with diabetes mellitus type 2 and oral cavity or oropharyngeal squamous cell carcinoma were treated and followed at our tertiary academic institution and the Veterans Affairs Greater Los Angeles Healthcare System from 1998 to 2012. Main Outcome Measure: Cox proportional hazards models and Kaplan-Meier curves were constructed to determine if metformin has an effect on disease recurrence after primary cancer treatment. Results: Metformin does not appear to have a significant effect on disease recurrence in patients with OC/OP SCC and diabetes mellitus type 2 (p = 0.53). Even when including only patients with stage I or II disease, metformin still did not decrease recurrence (p = 0.60). Conclusion: Herein, our data suggest that metformin use does not significantly impact time until recurrence for diabetic patients with OC/OP SCC.

经口腔入路腔镜甲状腺肿瘤切除术治疗甲状腺微小乳头状癌患者的优势基于血清甲状旁腺功能和免疫功能

目的探讨基于甲状旁腺功能和免疫功能经口腔入路腔镜甲状腺肿瘤切除术治疗甲状腺微小乳头状癌患者的优势。方法收集2022年2月—2023年4月在南阳市中心医院治疗的甲状腺微小乳头状癌患者90例,随机分为观察组(经口腔前庭入路腔镜手术,n=45)和对照组(颈部开放手术,n=45),分别对比两组患者手术总时长、术中失血量、术后引流量、疼痛评分、甲状旁腺功能和免疫功能指标以及两组患者的并发症发生率。结果观察组的手术总时长明显长于对照组,但术中失血量、术后引流量和疼痛评分均显著优于对照组(P<0.05)。在甲状旁腺功能方面,两组患者的甲状旁腺激素(PTH)和血清钙离子水平在手术后均有不同程度的下降,但观察组患者的PTH水平下降的程度更为轻微,差异具有统计学意义(P<0.05)。在免疫功能指标方面,手术前,两组患者的IgG和IgA水平差异无统计学意义(P>0.05),手术后观察组患者的IgG和IgA水平明显高于对照组患者,差异有统计学意义(P<0.05)。观察组患者的并发症发生率明显低于对照组患者(P<0.05)。结论相对于颈部开放手术,经口腔入路腔镜手术在治疗甲状腺微小乳头状癌方面具有明显的优势。经口腔入路腔镜手术创伤小、手术效果好、术后恢复快,且对甲状旁腺功能和免疫功能的影响更为轻微。因此,经口腔入路腔镜手术可以作为治疗甲状腺微小乳头状癌的首选方法之一。

Histone modifications:Targeting head and neck cancer stem cells

Head and neck squamous cell carcinoma(HNSCC) is the sixth most common cancer worldwide, and is responsible for a quarter of a million deaths annually. The survival rate for HNSCC patients is poor, showing only minor improvement in the last three decades. Despite new surgical techniques and chemotherapy protocols, tumor resistance to chemotherapy remains a significant challenge for HNSCC patients. Numerous mechanisms underlie chemoresistance, including genetic and epigenetic alterations in cancer cells that may be acquired during treatment and activation of mitogenic signaling pathways, such as nuclear factor kappa-light-chain-enhancer-of activated B cell, that cause reduced apoptosis. In addition to dysfunctional molecular signaling, emerging evidence reveals involvement of cancer stem cells(CSCs) in tumor development and in tumor resistance to chemotherapy and radiotherapy. These observations have sparked interest in understanding the mechanisms involved in the control of CSC function and fate. Post-translational modifications of histones dynamically influence gene expression independent of alterations to the DNA sequence. Recent findings from our group have shown that pharmacological induction of posttranslational modifications of tumor histones dynamically modulates CSC plasticity. These findings suggest that a better understanding of the biology of CSCs in response to epigenetic switches and pharmacological inhibitors of histone function may directly translate to the development of a mechanism-based strategy to disrupt CSCs. In this review, we present and discuss current knowledge on epigenetic modifications of HNSCC and CSC response to DNA methylation and histone modifications. In addition, we discuss chromatin modifications and their role in tumor resistance to therapy.

Translational aspects of themodern genetics in head and neck cancers

Oral cancer(OC)is one of the most recurrent cancers in the head and neck squamous cancer(SCCHN)category.Recently,the genome-wide association studies(GWAS)have gained growing interest in the scientific community.GWAS have identified several pathways involved in the interactions among general risk factors and genomic variants affecting SCCHN.This systematic overview aims to critically evaluate the latest data reported within the scientific literature.The aim was to investigate the impact of genetic aspects on SCCHN onset and prognosis,involving other clinical and systemic co-factors.PubMed,Google Scholar,and Cancer Genetics Web databases have been systematically investigated for original articles published in the last two years,reporting studies on the main queries addressed in this work.This review also comparatively describes the impact of environmental and pathological co-factors in different types of cancers,clarifying and updating the role of genetic factors in SCCHN onset and development.The main outcomes reported may be helpful to drive clinicians towards their clinical evaluations for the most appropriate therapeutic approach in SCCHN.

COVID-19 and oral cancer:Critical viewpoint

The outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has marked the beginning of a new pandemic named coronavirus disease 2019(COVID-19). The World Health Organization has announced it as a health emergency that is of international concern. The disease has been reported to cause respiratory illness, pneumonia and even hinder the immunity of an individual. Individuals with disturbed immune responses have been found to be quite susceptible to this viral infection. Oral cancer patients are also at high risk in this pandemic situation and might encounter severe detrimental outcomes. Angiotensin receptors, documented in studies as the path of entry of this virus, are highly expressed in the epithelial cells of oral mucosa, making the group of individuals with oral cancers even more vulnerable. Extracellular matrix metalloproteinase inducer is another potential target for SARS-CoV-2. An exhaustion of angiotensin converting enzyme 2 cell receptors leads to protumoral effects, whereas a downregulation of extracellular matrix metalloproteinase inducer leads to antitumoral effects. Thus, it causes a variation of the biological behavior of the tumor. This article focusses on the molecular mechanisms, effects and pathophysiology of COVID-19 in oral squamous cell carcinoma patients. The different molecular changes in oral squamous cell carcinoma in the background of COVID-19 will modify various environmental factors for this pathology and have an effect on the carcinogenesis process. Understanding the behavior of the tumor will help plan advanced treatment strategies for oral squamous cell carcinoma patients in the background of COVID-19.

Primary small cell neuroendocrine carcinoma of the right posterior tongue

Small cell neuroendocrine carcinoma(SNEC)is an extremely aggressive tumor and mainly occurs in the lung.Primary extra-pulmonary SNEC is rare.To date,only 11 primary SNECs occurring in the oral cavity have been reported in the English literature.We describe a case of primary SNEC of the right posterior tongue in a 46-year-old man.The patient had stage IVA disease and received adjuvant chemotherapy,followed by radical surgery and radiotherapy.He remained tumor-free for 20 mo before death due to gastrointestinal metastasis.The relevant literature on the 11 previously reported patients was reviewed,and the clinical features,histopathological characteristics,differential diagnosis and therapeutic strategies of this rare tumor were analyzed.

A Six-Year Review of Head and Neck Cancers at the Komfo Anokye Teaching Hospital, Kumasi, Ghana

Background: In Ghana, information on the prevalence and pattern of Head and Neck Cancers (HNCA) is scarce. There are few publications based on specific sub-sites of the head and neck, however, literature on the prevalence and pattern of HNCA in general is lacking. The present study aimed to describe the pattern of HNCA among patients seen at the multidisciplinary HNCA clinic of Komfo Anokye Teaching Hospital. Methods: This is a retrospective review of all consecutive patient records seen at the multidisciplinary clinic from 2004 to 2009. Results: There were 149 males and 103 females giving a male to female ratio of 1.45:1. The age range was 2 - 95 years with a mean of 48.1 years. The commonest type of HNCA in this review is cancers of the oral cavity (29.4%), followed by accessory sinuses (13.9%) and larynx (13.5%). Nasopharyngeal cancer affected young people, with 34.5% of affected patients aged between 10 and 19 years. The commonest histopathological type was squamous cell carcinoma (49.6%). Majority (47.6%) of patients presented at stage IV. Conclusion: The commonest HNCA is oral cancer. Majority of patients with HNCA are presenting late calling for public health education to raise awareness and promote early detection.

延长垂直下斜方肌岛状肌皮瓣修复重建大型头颈部缺损

颈横动脉供血的延长垂直下斜方肌岛状肌皮瓣(extended vertical lower trapezius island myocutaneous flap,eVLTIMF)用于修复重建大型头颈部缺损安全可靠。该瓣制备较简单,成活率高。供区较隐蔽,可直接关闭缝合,并发症少,肩部运动受影响较小;还可制备成折叠瓣,合并其他带蒂瓣或合并肩胛骨骨肌皮瓣修复特大洞穿性缺损或下颌骨缺损。eVLTIMF在头颈部大面积缺损修复,尤其是在晚期复发性头颈部肿瘤挽救手术后巨大缺损修复重建中起着重要作用。本文对斜方肌的临床应用解剖、 eVLTIMF瓣制备及其在颅颌面、口腔颌面和颌颈区缺损修复中的应用作一阐述。

HPV感染在口腔鳞癌中的研究进展

口腔鳞状细胞癌(OSCC)是头颈部最常见的恶性肿瘤,预后较差,整体5年生存率较低,世界卫生组织预计在未来十几年中OSCC的发病率将持续上升。除了烟草、槟榔、饮酒等因素,人乳头瘤病毒(HPV)感染也被确定为危险因素,HPV的感染与OSCC的发生及预后有着密切的关系,目前研究表明,HPV感染逐渐成为OSCC的主要致病因素。HPV感染引起的OSCC可能会成为OSCC中一种发病机制、肿瘤微环境、生物学行为和预后都相对独特的一种类型。笔者通过广泛查阅文献,围绕HPV在OSCC中作用机制、HPV阳性OSCC的特征及HPV与OSCC治疗和预防的相关性的研究进展进行总结。

铁蛋白重链1在头颈鳞癌中的表达及对口腔鳞癌增殖、迁移、侵袭的影响

目的:明确头颈鳞癌(head and neck squamous cell carcinoma,HNSCC)、口腔鳞癌(oral squamous cell carcinoma,OSCC)组织与癌旁组织中铁蛋白重链1(ferritin heavy chain 1,FTH1)的表达差异,分析FTH1表达与HNSCC、OSCC患者预后及临床病理特征之间的关系。在口腔鳞癌CAL-27细胞株中探讨其对OSCC的影响,为临床上OSCC的分子检测与治疗提供新的策略。方法:通过癌症基因组图谱数据库(The Cancer Genome Atlas,TCGA)下载HNSCC转录组数据样本及临床样本信息,使用R软件研究HNSCC肿瘤组织与正常组织中FTH1的表达差异,分析FTH1表达与HNSCC患者临床病理特征之间的关系。收集40例OSCC患者的癌及癌旁组织样本,通过RT-qPCR检测样本中FTH1的表达,明确FTH1在OSCC组织中的差异表达,结合患者临床病理特征进行相关性分析。选取人正常口腔黏膜上皮细胞系OMECs和口腔鳞癌细胞系CAL-27培养,进一步检测并明确FTH1在OSCC中的表达变化。体外实验研究FTH1对CAL-27细胞增殖、侵袭、迁移的影响,利用CCK-8实验观察FTH1对CAL-27增殖活性能力的作用,利用划痕愈合实验(Transwell小室实验)检测FTH1对CAL-27迁移和侵袭的作用,利用Matrigel Transwell实验检测FTH1对CAL-27侵袭的作用。结果:TCGA数据库结果显示,FTH1在HNSCC组织中表达显著高于癌旁组织(P<0.001),其表达与患者不良病理特征和不良预后相关(P<0.05)。FTH1在OSCC组织中的表达显著高于癌旁组织(P<0.001),其表达与患者颈淋巴结转移、病理分级、临床分期有关(P<0.05)。FTH1在CAL-27中的表达显著高于OMECs(P<0.001)。CCK-8实验结果显示,敲减FTH1可抑制CAL-27的增殖能力(P<0.05)。划痕愈合实验和Transwell小室实验结果显示,敲低FTH1可抑制CAL-27的迁移、侵袭能力(P<0.05)。结论:在HNSCC和OSCC中,FTH1基因表达上调,其表达与不良病理特征和不良预后有关。敲低FTH1基因将抑制CAL-27的增殖、迁移及侵袭能力,其在OSCC中可能发挥促癌作用。

颈淋巴清扫术保留胸锁乳突肌与否对晚期口腔鳞癌预后的影响

目的:探讨晚期口腔鳞状细胞癌(advanced oral squamous cell carcinoma,AOSCC)患者颈淋巴清扫术中是否保留胸锁乳突肌(sternocleidomastoid muscle,SCM)对预后的影响。方法:收集2013年1月至2017年6月广西医科大学附属口腔医院口腔颌面外科诊治的235例晚期(临床Ⅲ期和Ⅳ期)口腔鳞状细胞癌且接受颈淋巴清扫术患者的资料信息并进行回访,比较保留与切除SCM的两种不同颈淋巴清扫术式之间总生存期(OS)、局部无复发生存期(LRFS)以及颈部无复发生存期(RRFS)的差异。采用SPSS 25.0软件包对数据进行统计学分析。结果:235例患者中,101例术中保留SCM,134例切除SCM,2组5年生存率和5年颈部复发率无统计学差异。Kaplan-Meier法单因素分析结果显示,2组的OS、LRFS和RRFS之间均无统计学差异。Cox多因素回归分析进一步校正结果显示,是否切除SCM均不是OS、LRFS和RRFS的独立影响因素,N分期和术后放化疗是AOSCC患者OS、LRFS和RRFS的独立影响因素。结论:AOSCC患者颈部手术行保留SCM的颈淋巴清扫术对生存和复发(包括局部复发和颈部复发)均无影响,对转移淋巴结未侵犯SCM的AOSCC患者行保留SCM的颈淋巴清扫术是可行的;N分期和术后是否放化疗影响AOSCC的预后。

舌癌、口底癌非连续性颈淋巴清扫术后复发2例

头颈部鳞癌是一种常见的恶性肿瘤,全球发病率排名第六,每年新增病例约60万例。舌、口底癌约占口腔癌的50%,此区域解剖结构复杂、淋巴回流丰富,容易发生转移。颈淋巴清扫术和术后放化疗是控制颈部复发及转移最有效的方法。本文搜集2020—2022年延边大学附属医院舌、口底癌患者9例,9例患者均行“肿物扩大切除+颈淋巴结清扫术+前臂皮瓣移植术+术后放疗1个月”,其中2例复发。本文报告1例舌癌、1例口底癌术后复发患者,并且就舌、口底癌的术后复发问题进行探讨。

Sentinel node biopsy in early oral squamous cell carcinoma - a safe diagnostic and therapeutic procedure

Sentinel node biopsy(SNB)is considered the standard surgical procedure for detecting occult neck node metastasis in oral squamous cell carcinoma(OSCC)in many centers around the world.Due to the fact that this method removes and evaluates the first lymph node(s)reached by the lymphatic flow from the tumor area,this has raised the question of whether SNB could also be considered a therapeutic procedure by targeted lymphadenectomy instead of elective neck dissection(END).Compared to END,its safety and low morbidity have been established.However,the surgical management of the clinical node-negative(cN0)neck in T1/T2 oral carcinoma has been under ongoing debate due to the lack of randomized studies comparing SNB to END in terms of overall survival(OS),disease-free survival(DFS)and neck recurrence rates(NRRs).In the last years,two prospective randomized studies have proven with high-level evidence the noninferiority of SNB compared to END in terms of oncologic outcome while reducing costs and morbidity.In our opinion,SNB should be offered as the new standard therapeutic procedure in early OSCC.

Contralateral neck dissection in oral squamous cell carcinoma:when it should be done?

Oral cavity squamous cell carcinoma(OSCC)has a high incidence of cervical micrometastases and sometimes metastasizes bilaterally because of the rich lymphatics in the submucosal plexus,which freely communicate across the midline.The presence of contralateral pathologic lymph nodes has been reported previously as a critical factor influencing the survival of patients.There are a few reports in the literature with regard to the rates of contralateral neck disease and the factors that may be involved in the risk with them.An elective ipsilateral neck treatment is generally recommended for initial treatment in all OSCC.However,no consensus exists whether or not to perform an elective contralateral neck dissection or radiation.In this study,a systematic review has been performed in order to evaluate the predictive value of clinical-histopathologic factors potentially related to contralateral occult lymph node metastasis in squamous cell carcinomas of the oral cavity to form a rational basis for elective contralateral neck management.

Elective neck dissection in early oral squamous cell carcinoma:necessary?

Aim:The indication of neck dissection in oral squamous cell carcinoma(OSCC)is a problem of risk-benefit evaluation between probability of neck metastases,the problem of complications associated with neck dissection and the prognostic influence of delayed diagnosis of metastasis during follow-up.There is no consensus on the elective treatment of the neck in early oral cancer patients with a clinically N0(cN0)neck.Methods:The author performed a search of PubMed articles with the words"elective neck dissection vs.observation","node negative neck"and"early stage oral squamous cell carcinoma".The author selected those articles that studied the early OSCC(T1-T2),and elective neck treatment was compared with clinical observation.Results:Many studies have compared the outcome of elective neck dissection(END)to observation of the neck in early OSCC.The results of them are described.The biologic aggressiveness of oral cavity squamous cell carcinoma,particularly in the early stages,is reflected in its ability to metastasize to regional lymph node chains.Many pretreatment imaging techniques to diminish the incidence of occult metastases haven been studied,and comparative studies have shown ultrasound guided fine needle aspiration cytology(USgFNAC)to be the most accurate.Conclusion:A few non-randomized studies have shown no advantages of END when strict USgFNAC follow-up was employed.Thus,if routine strict follow-up using USgFNAC by a well-trained ultrasonographer cannot be assured,END is the safest strategy.

口腔鳞癌患者颈淋巴结cN_0的处理

目的 探讨口腔鳞癌颈淋巴结转移的发生规律及对cN0 患者的治疗原则。方法 通过对四川大学华西口腔医院颌面外科 1980～ 2 0 0 1年住院的 10 2 4例口腔鳞癌患者的临床资料进行回顾性分析。结果 口腔鳞癌患者颈淋巴结的总体转移率为 36 6 2 %,其中舌癌转移率最高为 42 82 %,颊癌和下牙龈癌相近分别为 31 93%和32 76 %,口底癌转移率最低为 2 5 .0 0 %;cN0 患者的颈淋巴结隐匿性转移率为 2 0 94%。口腔鳞癌的隐匿性转移与原发灶的部位、T分期等密切相关。结论 临床上应根据患者肿瘤原发灶的部位、大小和临床分期等综合考虑分析 ,判断颈淋巴结情况 ,从而选择合理的治疗方案。