Investigation of<Emphasis Type="Italic"> Helicobacter pylori</Emphasis> colonization in laryngeal neoplasia

Helicobacter pylori has been investigated in several other organ systems and localizations such as the oral cavity, but has not been investigated extensively in squamous cell carcinoma of the larynx, a region that could be directly exposed to the bacterium by the oral route or gastro-esophageal reflux. Only serological studies are available regarding the relation between H. pylori and laryngeal cancer, yielding conflicting results. To our knowledge, there is no study investigating the presence of H. pylori in laryngeal squamous cell carcinoma tissue. The purpose of this study was to investigate the presence of H. pylori in laryngeal squamous cell carcinoma tissue and to investigate the possible role of this organism in the etiopathogenesis of laryngeal cancer. Specimens from 50 patients with laryngeal cancer who underwent total or partial laryngectomy between March 1999 and December 2002 were examined by histopathological and immunohistochemical methods to detect H. pylori. The presence of H. pylori was also investigated histopathologically in 50 benign laryngeal biopsy specimens. In our study, we demonstrated that H. pylori was not present in laryngeal squamous cell carcinoma tissue or in the benign lesions. We could not find any evidence indicating that H. pylori played a role at the tissue level in the pathogenesis of laryngeal carcinoma.     

The expression of somatostatin receptors 1 and 2 in benign,pre‐malignant and malignant laryngeal lesions

The expression of somatostatin receptors 1 and 2 in benign, pre‐malignant and malignant laryngeal lesions The role of chemotherapy in squamous cell carcinoma of the larynx has not been clearly defined. Whilst toxic chemotherapy regimes may confer a marginal improvement in survival, surgery and radiotherapy remain the mainstay of treatment. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane‐bound receptor subtypes. The expression of somatostatin receptor subtypes (SSTRs) 1 and 2 was studied in benign, pre‐malignant and malignant laryngeal specimens. Epithelial expression of SSTR1 was detected in 4/6 (67%) Reinke's oedema, 5/6 (83%) pre‐malignant and 8/12 (67%) malignant specimens, with virtually no stromal or vascular expression. High levels of epithelial SSTR2 expression were noted in all Reinke's oedema specimens, compared with low‐to‐moderate levels in only 2/6 (33%) pre‐malignant and 3/12 (25%) malignant specimens (P < 0.01). This ‘loss’ of epithelial SSTR2 expression may provide a growth advantage in pre‐malignant and malignant laryngeal lesions. Vascular expression of SSTR2 was ubiquitous in all groups, with scant stromal expression. Overall, most (>80%) pre‐malignant and malignant laryngeal specimens expressed at least one of the two SSTR subtypes studied. Somatostatin analogues may have a therapeutic role in squamous cell carcinoma of the larynx.     

全自动细胞图像分析仪做喉鳞状细胞癌癌细胞核形态学定量分析

目的：定量分析喉鳞状细胞癌（LSCC）癌细胞核的形态,并探讨形态学参数与肿瘤临床的关系。方法：采用全自动细胞图像分析仪对来源于21例LSCC和20例喉部良性病变的83张细胞刷片做核形态定量研究。结果：LSCC癌细胞表现为较大的核面积、平均半径、核周长、核圆球度以及核单位面积DNA含量,其中核面积、核周长、核单位面积DNA含量在肿瘤发生不同部位及不同病理类型间有差异,喉部恶性肿瘤组织中s期细胞细胞核均在77μm^2以上,平均核半径和核面积作拟合抛物线（拟合方程Y=aX^2＋bX＋c）,提示b值越小（b〈0．045）,C值越大（c〉1．82）,则与肿瘤越相关。结论：核形态定量分析认为LSCC癌细胞表现为异常的核形态,结合S期细胞核面积与平均半径和核面积的抛物线拟合方程系数,在辅助细胞学诊断及临床评价肿瘤生物学特性方面意义较大。     

疱疹类病毒与喉良性及恶性上皮病变的关系

目的 :探讨疱疹类病毒在喉良恶性上皮病变中的作用。方法 :采用通用引物多聚酶链反应 (PCR)及原位多聚酶链反应 (PCR- ISH)对 12 8例喉良恶性病变进行了检测。结果 :PCR检测 12 8例标本 ,10例检出单纯庖疹病毒 1型 (HSV - 1) ,其中喉癌 3例 ,原位癌 1例 ,息肉 4例 ,角化症 2例 ,未检出爱泼斯坦病毒 (EBV)及巨细胞病毒 (CMV )。 10例阳性标本用 PCR- ISH定位检测 ,除 1例鳞癌和 1例原位癌阴性外 ,其余 8例均阳性 ,良性病变从基底层到浅层细胞核均阳性 ,癌症中则散在阳性 ,1例腺体细胞核也呈阳性。结论 :EBV及 CMV与喉病变无关 ;大部分喉良恶性上皮病变与 HSV- 1无关 ,但在少数患者 ,HSV - 1可能起诱发作用。     

Antigen retrieval: p53 staining in benign,pre-malignant and malignant tissues of the larynx

Antigen retrieval techniques have been reported to increase p53 detection. Using an antigen retrieval technique applied to immunohistochemistry, a study was performed on 67 laryngeal lesions (21 benign, 16 carcinoma in situ, 30 squamous cell carcinoma). p53 staining was observed in 30% of carcinoma in situ specimens and 53% of squamous cell carcinomas but was not detected prior to antigen retrieval in any benign lesion. However, over-expression of p53 was identified in 92.5% of benign lesions after antigen retrieval using the microwave oven heating. There was also increased p53 staining in both the carcinoma in situ (43.7%) and squamous cell carcinomas (30.0%) after antigen retrieval. We conclude that antigen retrieval using microwave oven heating increases immunohistochemical detection of p53 such that positive staining is observed in benign conditions. We postulate that this apparent over-expression is a manifestation of the wild-type protein, which may be found in more evidence in basal cells than suprabasal cells. Our results thus offer a cautionary note to such studies involving squamous cell cancers that attempt to correlate p53 over-expression with clinical parameters.     

Analysis of 2,500 squamous cell carcinoma of the head and neck

The purpose of this paper is to define the prevalence of squamous cell carcinoma of the head and neck as seen at the ENT Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain in the last years, studying 2500 cases. Relative frequencies at the various sites, age distribution, male to female ratios, TNM stage are reported. From the results we point out that laryngeal squamous cell carcinomas (1297 cases) were more than 50% of all tumors, followed by oropharygeal carcinomas, oral cavity carcinomas and hypopharyngeal carcinomas. The mean age was 61 years, and patients with nasopharyngeal carcinomas were the youngest. 92% of the patients were males, and the highest rate of males was seen in the larynx and hypopharynx (97% males). Only 9% of the patients were non-smokers and 18% were not alcohol drinkers. Hypopharyngeal squamous cell carcinomas concentrated the highest rate of patients with severe toxic consumption. A significant proportion of earlier tumors was only seen in the larynx and oral cavity (54% and 41% Stages I-II, respectively). On the other hand, hypopharyngeal carcinoma, oropharyngeal carcinoma and nasopharyngeal carcinomas were mainly diagnosed in advanced stages.     

Photodynamic therapy and the treatment of head and neck neoplasia

Objective: To present the theory, technique, and results of photodynamic therapy for the treatment of oral, laryngeal, and head and neck cancers. Study Design: Retrospective review of the literature of more than 500 patients with head and neck cancer treated with photodynamic therapy, as well as a retrospective review of the author's 107 patients treated with photodynamic therapy for head and neck neoplasia between 1990 and 1997. Methods: The literature was retrospectively reviewed, as were patient records, and tabulaled for age, sex, site, and staging of lesions, with special focus on post-photodynamic therapy treatment outcome, long-term disease-free survival, and complications. Results: Twenty-five patients with carcinoma in situ and T1 squamous cell carcinoma of the true vocal cord who underwent photodynamic therapy treatment for cure obtained a complete response after a single photodynamic therapy treatment. Only one patient has had recurrence to date, with a cure rate to 79-month follow-up of 95%. Twenty-nine patients with carcinoma in situ and T1 recurrent squamous cell carcinomas of the oral cavity and tongue were treated. All obtained a complete response after a single photodynamic therapy treatment; however, five patients developed local recurrence with follow-up to 70 months, for an 80% cure rate. A review of 217 patients with early squamous cell carcinomas of the head and neck treated with photodynamic therapy in the literature demonstrated an 89.5% complete response rate. The most common complication in these patients was limited prolonged skin photosensitivity without any permanent sequelae. Conclusions: Photodynamic therapy is effective for treating carcinoma in situ and T1 squamous cell carcinoma of the larynx and oral cavity and may be of benefit as an adjuvant intraoperative treatment of stages III and IV tumors of the head and neck in conjunction with surgery and radiation therapy to improve cure rates. Further controlled studies need to be performed to further demonstrate the effectiveness of photodynamic therapy and the treatment of head and neck cancers.     

Loss of FHIT expression in squamous cell carcinoma and premalignant lesions of the larynx

The tumor suppressor gene FHIT (fragile histidine triad) at chromosomal position 3p14.2 is altered by deletions in human tumors. The frequency and specificity of its inactivation vary among carcinomas, but few articles have referred to premalignant lesions such as dysplasia. We studied the expression of FHIT in a series of squamous cell carcinomas and premalignant lesions of the larynx. We observed 36 laryngeal carcinoma biopsy specimens and 70 dysplasia biopsy specimens. We studied FHIT expression in carcinoma and dysplasia with the immunohistochemical ABC (avidin-biotinylated peroxidase complex) method. Loss of FHIT protein was observed in 42% of the squamous cell carcinomas and 23% of the premalignant lesions. There was no significant difference among the three grades of dysplasia in FHIT expression. These findings of loss of FHIT protein expression, not only in squamous cell carcinoma, but also in premalignant lesions, indicate that FHIT alterations play an important role in the early events of carcinogenesis.     

Simultaneous squamous cell carcinomas of the oral cavity and oropharynx

INTRODUCTION: Squamous cell carcinoma of the oral cavity is often a single localization, but the discovery of another or several associated lesions is not exceptional. The goal of our study was a retrospective analysis of patients having 2 simultaneous squamous cell carcinomas of the upper aerodigestive tract (UADT), i.e. diagnosed during the same panendoscopy by excluding the esophagus and the lung. PATIENTS AND METHODS: Between 1995 and 2001, 1,129 patients were treated for squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx in the Bordeaux Maxillo-facial Surgery Unit. 1% of these patients presented 2 simultaneous squamous cell carcinomas of UADT. RESULTS: Our series was divided in 9 men (75%) and 3 women (25%) with an average age of 61.3 years (48-86). At the end of the study 2 patients were lost to follow-up, 3 patients were alive without recurrence, and 1 patient was alive with recurrence. The average follow-up time was 17.6 months. DISCUSSION: A review of the literature gave an incidence of simultaneous squamous cell carcinomas of UADT varying from 1.3 to 12.8% according to authors. Thus, any patient having squamous cell carcinoma of the UADT must be considered as having an important potential risk to present another simultaneous cancer and to benefit from a systematic panendoscopy. In spite of an early diagnosis, the prognostic of these lesions remains bad.     

Expression of calcium binding protein S100 A7 (psoriasin) in laryngeal carcinoma

Many studies have reported increased expression of S100 A7 (psoriasin) in neoplastic lesions. Among them are studies on breast carcinoma, bladder squamous cell carcinoma, skin tumors and oral cavity squamous cell carcinoma. The expression of S100 A7 has not been described for laryngeal cancer.Objective: This study aims to identify the expression of the calcium-binding protein S100 A7 and its correlation with squamous cell carcinomas of the larynx.Material and Methods: Specimens from 63 patients were submitted to immunohistochemistry testing with antibody S100 A7. Results were classified and compared.Results: The group with highly differentiated tumors had the highest treatment failure scores. Moderately differentiated tumors had higher treatment failure scores than poorly differentiated tumors. Higher scores were predominantly seen on stages I and II in moderately differentiated tumors, whereas score distribution was more homogeneous in advanced stage disease (III and IV). Regarding failure in treatment, the group scoring zero (3/4 complications: 75%) differed significantly from the remaining groups (13/59: 22%).Conclusions: S100 A7 marker was expressed in 93.7% of laryngeal cancer cases, with higher positive correlation rates in more differentiated tumors and significantly lower rates of treatment failure. Scores had no impact on survival rates.     

α-甲基酰基辅酶A消旋酶在喉癌中的表达

目的研究α-甲基酰基辅酶A消旋酶(AMACR)在喉癌中的表达,初步探讨AMACR在喉鳞癌生物学行为中的意义。方法用免疫组织化学EliVisionTMplus二步法(福州迈新)检测40例原发喉鳞癌、20例声带息肉及10例癌旁组织中AMACR的表达情况。结果40例喉癌中13例(32.5%)存在不同程度的AMACR表达,在20例声带息肉和10例正常喉组织中无AMACR表达,差异有统计学意义(P<0.01)。AMACR在高分化鳞癌和中、低分化鳞癌中表达的阳性率分别为50%、15%,差异有统计学意义(P<0.05),Ⅰ、Ⅱ期与Ⅲ、Ⅳ期喉癌AMACR阳性率无统计学意义,AMACR表达与性别、肿瘤部位、颈淋巴结转移无统计学意义(P>0.05)。结论AMACR在喉鳞癌中有阳性表达,其表达可能与分化有关,与性别、部位、临床分期、颈淋巴结转移无明显相关性。     

Carcinogenesis of laryngeal carcinoma

Experimental models have been developed for the induction of carcinoma of the larynx and for the study of its pathogenesis. The hamster has been the animal of choice. Polynuclear hydrocarbons, administered intratra-cheally, induce mostly squamous cell carcinomas. Diethylnitrosamine given systemically induces papillary tumors; some other N-nitroso-compounds given topically or systemically also induce laryngeal tumors, including carcinomas. Cigarette smoke inhalation induces preneoplastic and early neoplastic lesions of the larynx, including some invasive carcinomas. In vivo and in vitro methods have been developed for the morphological and biochemical study of target tissues in respiratory epithelial carcinogenesis to identify critical pathogenetic steps and their inhibition. These methods are now applicable to the in vitro study of human laryngeal epithelium and its susceptibility to cancer induction and prevention.     

Changing patterns of failure of head and neck cancer

BACKGROUND: With the increased use of neoadjuvant therapy for advanced stage squamous cell carcinoma of the head and neck, we have observed an apparent change in the pattern of failure from predominantly locoregional sites to distant metastases. We reviewed the patterns of failure in cancers of the oral cavity, oropharynx, and larynx at our institution during the last decade. OBJECTIVE: To determine whether there has been a significant change in the patterns of recurrence from the historical locoregional failure to distant sites, and whether this change is associated with the increased use of multimodality therapy. METHODS: We reviewed cancer registry data on patients with squamous cell carcinoma of the head and neck diagnosed between January 1, 1988, and December 31, 1999. Sites included the oral cavity and oropharynx (including the tongue, floor of mouth, retromolar trigone, gingiva, tonsil, and lip) and larynx. RESULTS: Among 432 patients with squamous cell carcinoma of the head and neck, 280 (65%) had oral cavity and oropharyngeal cancers, and 152 (35%) had laryngeal cancers. Overall, 19% developed locoregional recurrence, and 8% developed distant failure. Although locoregional failure for oral cavity and oropharyngeal squamous cell carcinoma decreased from 26% to 16% from 1988-1993 to 1994-1999, distant failure increased significantly from 3% to 8%. During these periods, multimodality therapy was used in 62% of oral cavity and oropharyngeal cancers, and this rate remained essentially unchanged. For laryngeal cancer, locoregional and distant failure remained stable at 18% and 9%, respectively. In these laryngeal cancers, the use of multimodality therapy decreased from 60% to 46%, but this difference was not statistically significant (P =.43). CONCLUSIONS: Although locoregional control in oral cavity and oropharyngeal cancers has improved significantly with the use of multimodality therapy, the incidence of distant failure has doubled. In laryngeal squamous cell carcinoma, the patterns of failure have not changed significantly.     

The expression of somatostatin receptors 1 and 2 in benign,pre-malignant and malignant laryngeal lesions

The role of chemotherapy in squamous cell carcinoma of the larynx has not been clearly defined. Whilst toxic chemotherapy regimes may confer a marginal improvement in survival, surgery and radiotherapy remain the mainstay of treatment. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane-bound receptor subtypes. The expression of somatostatin receptor subtypes (SSTRs) 1 and 2 was studied in benign, pre-malignant and malignant laryngeal specimens. Epithelial expression of SSTR1 was detected in 4/6 (67%) Reinke's oedema, 5/6 (83%) pre-malignant and 8/12 (67%) malignant specimens, with virtually no stromal or vascular expression. High levels of epithelial SSTR2 expression were noted in all Reinke's oedema specimens, compared with low-to-moderate levels in only 2/6 (33%) pre-malignant and 3/12 (25%) malignant specimens (P < 0.01). This 'loss' of epithelial SSTR2 expression may provide a growth advantage in pre-malignant and malignant laryngeal lesions. Vascular expression of SSTR2 was ubiquitous in all groups, with scant stromal expression. Overall, most (>80%) pre-malignant and malignant laryngeal specimens expressed at least one of the two SSTR subtypes studied. Somatostatin analogues may have a therapeutic role in squamous cell carcinoma of the larynx.     

Collision tumor of a hypopharyngeal adenoidcystic carcinoma and a laryngeal squamous cell carcinoma

INTRODUCTION: Malignancies in head and neck cancer are mainly squamous cell carcinomas. Adenoid cystic carcinomas are rare lesions of this site. Laryngeal adenoid cystic carcinoma is estimated to occur in 0.1 - 0.7 % of all laryngeal carcinomas. Adenoid cystic carcinomas are rarely located in the hypopharynx. To our knowledge there is no case report of adenoid cystic carcinoma of the hypopharynx as part of a collision tumor of the larynx. CASE REPORT: A 47-year-old male patient was diagnosed with an adenoid cystic carcinoma of the hypopharynx and a squamous cell carcinoma of the larynx. Because of local extension of both tumors laryngectomy and partial pharyngotomy with bilateral neck dissection was performed followed by radiation therapy. Clinical aspects as well as histomorphological and immunohistochemical criteria of both tumor entities are discussed. DISCUSSION AND CONCLUSIONS: Immunohistochemical characteristics showed two different carcinoma entities in the larynx and hypopharynx. Only by complete histological investigation of a carcinoma those rare cases of a collision tumor can be detected. Both tumor entities need to be considered for therapy strategy and oncological follow-up planning.     

幽门螺杆菌感染和喉鳞状细胞癌致病因素的研究

目的 探讨幽门螺杆菌(Helicobacter pylori,Hp)在喉鳞状细胞癌患者中的感染情况,分析HP感染是否为喉鳞癌的致病因素.方法 采用巢式聚合酶链反应(nested PCR,nPCR)技术和Hp培养、鉴定对30例喉癌患者和15例喉良性疾病(声带息肉和会厌囊肿)患者的喉黏膜进行Hp检测.结果 采用nPCR法检测Hp,喉癌患者肿瘤组织Hp阳性22例(73.3%)高于对照组3例(20.0%),两者差异有统计学意义(x2=11.520,P=0.010).在22例Hp(+)的喉癌患者的44份肿瘤和癌旁组织中,有19份癌旁正常组织检出Hp(86.4%),而10份肿瘤组织检出Hp(45.4%),两者差异有统计学意义(x2=4.697,P=0.030).所有标本Hp培养均为阴性.结论 Hp在喉癌患者中的感染率明显高于实验人群,可能是喉癌的致病因素之一.     

Neuropilin-1在喉癌组织及喉癌细胞系中的表达

目的：探讨Neuropilin-1（NRP-1）在喉癌组织及喉癌细胞系中的表达及意义。方法：采用免疫组织化学法检测NRP-1在喉癌及癌旁组织中的表达;采用RT-PCR检测NRP-1mRNA在喉癌、癌旁组织及喉癌细胞系中的表达。结果：免疫组织化学检测发现28例喉癌组织标本中NRP-1均为高表达,而相应的癌旁组织则无表达;RT-PCR检测NRP-1mRNA的表达结果显示28例喉癌组织中24例呈阳性表达,Hep-2细胞系呈阳性表达,相应的癌旁组织为阴性表达。结论：NRP-1表达于大多数喉癌组织及喉癌细胞系Hep-2中,而在癌旁组织不表达,提示NRP-1的表达可能与喉癌的发生、发展密切相关,且有较高的肿瘤特异性。     

DNA-flow cytometry of head and neck carcinoma: the importance of uniform tissue sampling and tumor sites

Summary Flow cytometric DNA ploidy measurements using deparaffinized tumor specimens were performed on 46 squamous cell carcinomas of the head and neck, including 22 carcinomas of the oropharynx, 18 carcinomas of the larynx and six carcinomas of the oral cavity. Aneuploidy was found in 14 of these tumors with carcinomas of the larynx and oral cavity showing almost equal percentages of DNA aneuploidy (10/18 and 3/6, respectively). In contrast, only 1 of the oropharyngeal carcinomas was aneuploid. Accurate microscopy-controlled sampling of tumor tissue from the histological tissue blocks was found to be mandatory in order to obtain reliable ploidy measurements.     

表皮生长因子受体3和4在喉鳞状细胞癌中的表达及意义

目的：探讨表皮生长因子受体3（ErbB3）与ErbB4基因在喉鳞状细胞癌中的表达及其与喉癌生物学、临床病理特征的关系。方法：采用RT-PCR法,分别对36例喉鳞状细胞癌患者的癌组织、14例切缘正常黏膜及11例良性增生性病变中ErbB3与ErbB4基因的表达进行检测。结果：在喉癌与良性增生性病变中,ErbB3 mRNA过度表达阳性率分别为66.7%和18.2%（P〈0.01）;ErbB4 mRNA过度表达阳性率分别为25.0%和9.1%（P〉0.05）。ErbB3和ErbB4在喉癌组织与切缘正常黏膜中的表达差异均无统计学意义（均P〉0.05）。ErbB3与ErbB4的表达与喉癌的临床病理特征无显著相关。结论：ErbB3与ErbB4在喉癌的发生、发展中具有不同的作用,在切缘正常黏膜中的过度表达对肿瘤复发可能起着一定的作用。     

Observing stage‐shifts in head and neck squamous cell carcinoma from initial clinical outpatient staging to definite clinical tumour board staging using radiological and endoscopical investigations: will less do?

Clin. Otolaryngol. 2011, 36 , 352–360 Objectives: Staging head and neck squamous cell carcinoma usually is initiated in the outpatient department (OPD) using patient history and physical examination. To reach consensus on stage and therapy, imaging and panendoscopy are more or less routinely applied as additional staging tests. Staging results from the outpatient department were evaluated for tumour and neck stage. We investigated in which situations additional staging tests are needed. Design: Prospective cohort study. Setting: Head and Neck Oncology Group, University Medical Centre. Participants: Of 341 patients, initial staging results from the outpatient department were compared with the ultimate staging results from the tumour board review, which provides the basis for decisions on therapy. Main outcome measures: Tumour stage and neck stage migrations during this staging tract. Results: In staging head and neck tumours are squamous cell carcinomas, additional staging tests like imaging and/or panendoscopy remain necessary to evaluate the primary tumour stage. Average accuracies of T‐staging in oral cavity, pharynx and larynx only amount to 71%, 47% and 61%, respectively. For T1N0 and T2N0 oral cavity tumours, neck assessment in the outpatient department was accurate in 100% (95% CI: 91–100%) and 93% (95% CI: 80–98%), respectively. In the larynx group, this was 100% (95% CI: 91–100%) and 97% (95% CI: 86–100%), respectively. Conclusions: For oral cavity and laryngeal tumours staged as T1‐2N0 in the outpatient department, we concluded that the outpatient department staging is highly predictive of the final pre‐treatment staging. In these cases, computer tomography and/or MRI remain a necessity but additional ultrasound with or without fine needle aspiration cytology can be omitted. In our institution, this would have resulted in a 46% reduction in ultrasound procedures. If T‐stage is upgraded during imaging or panendoscopy, additional staging tests for N‐stage should still be considered.