Long-term results of a phase II trial of induction chemotherapy with uracil-ftegafur (UFT), vinorelbine, and cisplatin (UFTVP) followed by radiotherapy concomitant with UFT and carboplatin (RT/UFTJ) in a primary site preservation setting for resectable locally advanced squamous cell carcinoma of larynx and hypopharynx

OBJECTIVE: We present long-term results of a phase II trial of induction chemotherapy (IC) with uracilftegafur (UFT) 200 mg/m orally days 1 to 21, vinorelbine 25 mg/m intravenously (IV) days 1 and 8, and cisplatin 100 mg/m IV day 1 (UFTVP) each for 21 days for 4 courses, followed by radiotherapy concomitant with UFT 100 mg/m orally daily and carboplatin (area under the curve [AUC] = 0.5 IV weekly) (RT/ UFTJ), without surgery to the primary site if response, in patients (pts) with resectable locally advanced squamous cell carcinoma of the larynx and hypopharynx. The primary endpoint was clinical complete response (CR) to induction UFTVP, and secondary endpoints were long-term overall survival (OS) and survival with primary site preservation (SPP). RESULTS: Between 1994 and 1997, 37 pts were included. CR to IC was 54% (95% confidence interval [CI] 43-65%). Main toxicity of UFTVP was G 3,4 neutropenia (73% of pts, 16% developed febrile neutropenia). After IC, primary site was treated with RT in 29 pts: 20 of them received RT/UFTJ (main toxicity mucositis G 3,4 70%). No pt died during treatment. Actuarial 5-year OS and SPP were 57% and 37%, respectively. CONCLUSIONS: This approach has significant activity and acceptable toxicity for achieving promising long-term OS and SPP and deserves further investigation.     

保留喉功能的下咽癌手术后缺损的修复

目的初步探讨在保留喉功能的下咽癌手术中,肿瘤切除后局部创面的修复方式。方法回顾性分析2013年3月~2018年3月33例下咽癌患者行保留喉功能肿瘤切除术后的临床资料,其中14例采用局部黏膜拉拢缝合,2例采用胸骨舌骨肌筋膜瓣修复缺损,4例采用异种牛脱细胞真皮基质修复膜,2例采用胸大肌皮瓣修复,4例锁骨上岛状皮瓣修复缺损,4例采用游离股前外侧皮瓣修复缺损,3例采用食管内翻拔脱胃上徙手术;观察缺损修复后患者伤口的愈合情况。结果33例患者喉功能良好,3例患者早期有轻微误吸,锻炼2周后即可正常进食。全部患者恢复吞咽功能,食管入口狭窄2例,后经局部扩张好转。咽瘘2例,局部换药1个月愈合。所有患者术后随访1年以上,生存率为78.79%（26/33）,目前正在随访中。结论在保留喉功能的下咽癌手术中,防止误吸和避免咽食管狭窄是肿瘤切除后修复的主要目标;根据患者的具体情况,选择适合患者的个体化修复方法,既可以恢复下咽的结构和功能,还可以避免不必要的副损伤。     

Esophageal reconstruction with larynx preservation using forearm-free flap

Surgery for cervical esophageal malignancy frequently involves comcomitant total laryngectomy carried out because of either oncologic or functional concerns. Though uncommon, preservation of the larynx has, in recent years, been described in patients undergoing cervical esophagectomy with reconstruction of the resulting circumferential esophageal defect achieved using either free jejunal flaps or gastric pullup procedures. The use of tubed-free cutaneous flaps for circumferential cervical esophageal reconstruction, however, has been rarely described in situations where the larynx has been preserved. We describe successful use of a tubed radial forearm-free flap for reconstruction of a circumferential cervical esophageal defect with preservation of the larynx. Use of the radial forearm flap in this situation resulted in minimal donor site-related morbidity, avoided the need for laparotomy and excellent voice and swallowing function were maintained. As such, use of tubed cutaneous free flaps can be considered an option for cervical esophageal reconstruction when the larynx has been preserved.     

诱导化疗在局部晚期下咽癌治疗中的意义

下咽癌发生位置隐蔽,早期症状不明显,超过2/3的下咽癌临床上初诊时为中晚期,是头颈肿瘤中预后较差的一种恶性肿瘤。近年来,倡导手术、放疗与化疗相结合的综合治疗模式以改善预后。诱导化疗在器官保留以及减少远处转移上的治疗价值日渐受到重视。但在实际临床工作中,主管医师对指南和各治疗手段利弊的理解以及临床经验的差异,诱导化疗在局部晚期下咽癌治疗中的作用仍存在争议。如何根据患者的全身和局部情况在众多的治疗方法中选择最合理的治疗手段是下咽癌治疗过程中一直在探讨的问题。通过文献回顾和个案剖析讨论诱导化疗在局部晚期下咽癌治疗中的作用。     

Organ preservation in locally advanced head and neck cancer of the larynx using induction chemotherapy followed by improved radiation schemes

The present prospective study seeks to evaluate overall and disease free survival, response and organ preservation rate, and toxicity of an intensive chemotherapy regimen (CT) followed by unconventional radiotherapy (RT) in patients with locally advanced operable head and neck cancer. Between January 1998 and December 2006 (June 2005), 115 patients with locally advanced, operable head and neck cancer were evaluated. A total of 333 cycles of neoadjuvant CT (cisplatin–5FU, days 1, 14, 28) followed by hyperfractionated/accelerated radiotherapy were given to 108 patients. A total of 108 patients were evaluable and received the planned CT–RT treatment. Two months after the end of RT, 97.2% of patients had a clinical complete remission of the primary and 67.5% of the neck node site. The overall survival was 55% and cause-specific survival was 73% at 5 years. Of the 33 relapsed patients, 12 recurred only at the primary site and 10 patients had distant metastases. The overall organ preservation rate was 73.5%. The chemotherapy regimen reported an overall cardiotoxicity from 5FU in 14% of patients, with severe toxicity in 3%. The radiotherapy schedule developed 84% of Grade 3–4 mucositis in the observed patients. The accelerated CT–RT regimen is able to achieve a high rate of larynx preservation, a good tolerability, and a satisfactory cause-specific overall survival.     

Medical malpractice and cancer of the larynx

OBJECTIVE: To analyze the frequency, clinical characteristics, and legal outcomes of malpractice litigation initiated by patients with cancer of the larynx. STUDY DESIGN: Retrospective review of 23 jury verdict reports from 11 states. METHOD: Jury verdict reviews from 1976 to 1997 were obtained from a computerized legal database compiled from all state and federal civil court decisions. Reviews compile pertinent data on defendants, plaintiffs, verdict outcomes, indemnity payments, allegations of wrongdoing, and provide case summaries. RESULTS: Delays in diagnosis were alleged in 19 of 23 (83%) suits. Hoarseness was present in 10 of 19 (53%), a neck mass in 3 of 19 (16%), and no biopsy was taken in 11 of 19 (58%) of those delayed. Mean age was 47 years, with a peak incidence in the general population of 70 to 74 years. Laryngectomy was alleged to be a result or complication of delay in 12 of 19 (63%). Over half of the patients delayed received compensation, and over half of the defendants were in general practice. Outcome was poor with a 35% mortality and a total of 47% either dead of disease or alive with disease. Complications, incorrect diagnosis, and informed consent did not play a significant role in initiating litigation. CONCLUSIONS: The delayed diagnosis of cancer of the larynx associated with litigation is frequently seen in younger patients presenting with hoarseness or neck masses. These patients frequently have poor outcomes. Patients with symptoms of cancer of the larynx must be aggressively evaluated regardless of age. Risk management goals to prevent delays in diagnosis may help prevent subsequent litigation.     

Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial)

A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m² paclitaxel, 100 mg/m² cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56–70 Gy in 5.5–7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4–72.2%), after 42 months was 56.5% (95% CI, 44.2–68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9–55.0%); after 42 months, 41.3% (95% CI, 29.3–53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials. This trial was initiated and conducted by the German Larynx Organ Preservation Study Group (DeLOS) which was founded as collaboration between head and neck surgeons and radiation oncologists to focus on the role of multimodality treatment in advanced laryngeal and hypopharyngeal cancer in Germany.     

Advanced hypopharyngeal cancer with amyotrophic lateral sclerosis

We present a case of advanced hypopharyngeal cancer occurring in a patient with amyotrophic lateral sclerosis (ALS). A 58-year-old man diagnosed with ALS 2 years previously noticed a mass in his neck and dysphagia. We diagnosed him as having hypopharyngeal squamous cell carcinoma with the left cervical lymph node metastases (T3N2bM0) and treated with concurrent chemoradiotherapy. During and after the treatment, his neurological symptoms showed no worse signs. The patient has been cancer-free for 13 months after concurrent chemoradiotherapy. The influence of ALS on the patients’ quality of life (QOL) and/or prognosis had to be taken into consideration when determining an appropriate treatment for the hypopharyngeal cancer. To the best of our knowledge, this may be the first case with ALS who was treated for hypopharyngeal cancer.     

Laminin-5 immunohistochemical mapping for analysis of local extension in hypopharyngeal cancer: A preliminary report

Objective

Laminin-5 γ2 chain (LNγ2) plays an important role in cancer differentiation and migration. Using a novel immunohistochemical mapping technique to investigate whole mucosal strips of total laryngopharyngectomy specimens using iodine, H–E, and LNγ2 stainings, we investigated the locoregional behavior of hypopharyngeal cancer.

Methods

Surgical specimens from two patients with pyriform sinus cancer were investigated. Three percent iodine was applied to the tumor-bearing laryngopharynx during surgery and photographed. Stainabilities of H–E and LNγ2 on pathologic sections from all mucosal strips were scored and coordinated with the laryngopharyngeal photograph to illustrate the immunohistochemical map.

Results

In both patients, the main tumor of invasive squamous cell carcinoma was circumferentially surrounded by a superficial lesion characterized by high grade intraepithelial neoplasia that remained unstained by iodine. On LNγ2 immunohistochemical mapping, the main tumor was demonstrated by Score 2 staining and the superficial lesion by a stronger Score 3 staining.

Conclusions

The finding of neoplastic cells at the periphery demonstrating a higher potential than the cancer cells at the tumor center is suggestive of impending progression from neoplasia to carcinoma. The current preliminary report suggested morphological evidence of intraepithelial infiltration and lateral invasion in hypopharyngeal cancer.     

下咽癌术后下咽缺损修复方法的选择

目的 :探讨下咽癌术后下咽缺损Ⅰ期修复的方法。方法与结果 :对 31例下咽癌术后下咽缺损患者行Ⅰ期修复 ,其中下咽、喉和食管颈段切除加胃造瘘术 1例 ,无咽瘘发生 ;直接缝合修复 17例 ,吞咽功能良好 15例 (88.2 % ) ;组织移植修复 13例 ,吞咽功能良好 6例 (46 .2 % )。同时行喉功能保存性手术 14例 ,吞咽功能良好9例 ,均为直接缝合修复病例 ;吞咽功能差 5例 ,2例为直接缝合修复病例 ,3例为组织移植修复病例 ,均发生误吸。结论 :直接缝合大多数吞咽功能良好。对下咽全缺损的修复 ,胃肠上徙比肌皮瓣优越。同时行喉功能保存性手术 ,必须严格选择病例 ,并把误吸的预防放在首位。下咽、喉和食管颈段切除加胃造瘘术有助于扩大下咽癌的手术适应证。     

下咽癌共病食管癌的高危因素及预后分析

目的 探讨下咽癌共病同时性食管癌的高危因素及预后。 方法 2011年1月至2014年3月诊治的200例下咽癌患者作为研究对象,回顾性分析患者的一般资料、肿瘤信息和随访情况。先对可能影响下咽癌共病同时性食管癌的危险因素进行单因素分析,组间比较采用卡方检验,进一步将有统计学差异的因素纳入Logistic回归分析。生存率的分析采用Kaplan-Meier法。 结果 单因素分析发现,年龄(<55岁)、男性、重度吸烟史、重度饮酒史和肿瘤侵犯部位≥3个是下咽癌患者共病同时性食管癌的高危因素(P<0.05)。多因素分析结果显示,年龄(<55岁)、重度吸烟史、重度饮酒史和肿瘤侵犯部位≥3个是下咽癌患者共病同时性食管癌的独立危险因素(P<0.05)。200例下咽癌患者中位生存时间仅为37.5个月,5年生存率仅为36.7%。56例下咽癌共病同时性食管癌患者中位生存时间为24.8个月,低于下咽癌不伴同时性食管癌患者(P<0.05)。早期食管癌(0+Ⅰ期)患者的中位生存时间为29.2个月,明显高于进展期食管癌(Ⅱ+Ⅲ期)的15.8个月,差异有统计学意义(P<0.05)。 结论 下咽癌共病同时性食管癌患者的生存时间较低。年龄(<55岁)、重度吸烟史、重度饮酒史和肿瘤侵犯部位≥3个是下咽癌患者共病同时性食管癌的独立危险因素,临床上应该针对这些高危因素进行早期干预。     

下咽癌侵犯颈段食管的治疗

目的 探讨下咽癌侵犯颈段食管的最佳治疗方案和处理经验。 方法 通过回顾性分析71例累及颈段食管的下咽癌患者临床资料,总结几种安全有效的治疗方式。71例均行颈淋巴结清扫术,切除患侧甲状腺37例,保留喉功能28例,全喉切除气管造瘘31例,喉气管代下咽食管12例。消化道重建方法有胸大肌肌皮瓣22例、喉气管瓣修复12例、裂层皮片或生物修复膜+胸大肌肌皮瓣6例,全食管切除后胃或结肠代食管31例。术后接受局部放疗(55~70 GY)65例。 结果 术后病理均为鳞状细胞癌,其中高、中、低分化分别为21例、18例、32例。淋巴结转移率45.2%,切除甲状腺37例中病理查见肿瘤14例,占比37.8%,甲状腺受侵犯占总病例19.7%。喉功能保留占39.4%,保留喉功能的患者中拔管率67.8%,术后咽瘘12例,刀口感染2例,吻合口狭窄1例。kaplan-meier生存率统计所有病例总的3年和5年无瘤生存率为43.7%和23.9%,其中喉功能保留组分别为50%和28.6%,喉功能不保留组分别为39.5%和20.9%。两组比较差异无统计学意义(χ²=1.244,P=0.265)。 结论 下咽癌侵犯颈段食管的治疗以手术+放疗的综合治疗为主,胸大肌肌皮瓣、喉气管瓣、全食管切除胃或结肠代食管的手术方式安全有效,部分患者采用合适的手术方式可以保留喉功能。     

下咽癌中差异表达的蛋白激酶及其抑制剂的生物信息学筛选

目的 筛选下咽癌中差异表达的激酶基因及其选择性抑制剂,为下咽癌的分子靶向治疗提供新的参考。 方法 利用GEO数据库和SAM软件筛选下咽癌中差异表达的激酶基因,体外培养人下咽癌FaDu细胞系。为验证GEO数据库中芯片结果的准确性,利用实时定量聚合酶链反应(Real-time PCR)检测差异表达激酶在FaDu细胞中的表达量,通过KEGG数据库获得激酶调控的通路,利用激酶抑制剂数据库和文献挖掘筛选获得在下咽癌FaDu细胞系中差异表达激酶的选择性抑制剂。 结果 (1)在GEO数据库的下咽癌基因组表达谱中,共筛选出3个高表达的激酶基因,分别为PKC-β、CDK6和CDC42(差异倍数≥2.0且P<0.05);(2)Real-time PCR结果显示在人下咽癌FaDu细胞中这3个上调激酶基因也出现高表达(P<0.05),证明全基因组的结果准确;(3)KEGG通路分析的结果显示3个高表达激酶调控复杂的通路网络;(4)激酶抑制剂的筛选结果显示共有5个激酶抑制剂调控PKC-β, 4个激酶抑制剂调控CDK6,3个激酶抑制剂调控CDC42。文献挖掘的结果显示在这12个激酶抑制剂中,有4个在癌症方面的研究较少,文献<10篇。 结论 下咽癌中共有3个激酶PKC-β、CDK6和CDC42发生高表达,并发挥促癌作用。它们的激酶抑制剂可能有潜在的抗癌作用,为下咽癌的分子治疗提供新的切入点。     

352例下咽癌综合治疗分析

,高、中、低分化分别为84例、163例、105例;淋巴转移为239侧.结论 下咽癌以综合治疗为主,在安全彻底切除肿瘤的前提下,保留喉的正常部分,重建恢复喉全部或部分功能,可提高患者生活质量和术后生存率.