DNA methylation and histone modification relate to RASSF1A gene deletion in laryngeal carcinoma tissues / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the relationship between RASSF1A gene expression and DNA methylation or histone modification in laryngeal carcinoma tissues.</p><p><b>METHODS</b>Chromatin immunoprecipitation (ChIP), methylation specific polymerase chain reaction (MSP) and realtime quantitative reverse transcription polymerase chain reaction (realtime RT-PCR) were used to analyze RASSF1A gene promoter region histone H3 lysine 9 methylation, H3 lysine 4 methylation, H3 lysine 9 acetylation, DNA methylation, and RASSF1A gene expression in laryngeal carcinoma tissue of 50 cases.</p><p><b>RESULTS</b>DNA methylation rate of gene RASSF1A was 62% in 50 cases of laryngeal carcinoma, but no DNA methylation was found in normal control group, with a significant difference (χ(2) = 15.381, P < 0.05). DNA methylation had no correlation with age, gender, differentiation degree, T stage, pathological type and lymph node metastasis (P > 0.05). The affection of DNA methylation group was more than unmethylation group to expression of gene RASSF1A (t = -3.108, P < 0.01). There was positive correlation between RASSF1A deletion and gene hypermethylation or between H3 lysine 9 methylation of RASSF1A gene promoter and DNA methylation in laryngeal carcinoma tissue(r = 0.816, P < 0.05), but there was negative correlation between H3 lysine 4 methylation of RASSF1A gene promoter and DNA methylation (r = -0.837, P < 0.05) and no correlation between H3 lysine 9 acetylation and DNA methylation (r = -0.383, P > 0.05).</p><p><b>CONCLUSIONS</b>Laryngeal tumor suppressor gene RASSF1A promoter methylation is a key factor down-regulating the gene expression, and histone modifications also plays an important role in tumor development.</p>

Extracapsular spread in ipsilateral neck metastasis: an important prognostic factor in laryngeal cancer / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the impact of extracapsular spread (ECS) in ipsilateral neck metastasis on prognosis and its related factors in laryngeal cancer.</p><p><b>METHODS</b>The study included 184 patients who underwent laryngectomy and simultaneous radical or modified radical neck dissection between January 1994 and December 1997 for laryngeal cancer. All of them had a complete 5-year follow-up. We used transparent lymph node detection and continuous slicing method on all neck dissection specimens. Kaplan-Meier model was used for survival analysis and the log-rank test was used to assess significance.</p><p><b>RESULTS</b>We found pathological neck metastases in 80 patients. Among them, 26 cases (32.5%) had ECS in ipsilateral neck. ECS incidence increased with advanced pathological N (pN) stages (pN1 3.7%, pN2a 25.0%, pN2b 50.0%, and pN2c 55.6%; P = 0.001). ECS incidence also increased with number of positive nodes (1 positive node 8.6%, 2 positive nodes 33.3%, 3 and more positive nodes 66.7%; P < 0.001). Incidences of contralateral neck metastases and ipsilateral neck recurrence in patients with ECS were higher than those in patients without ECS (46.2% vs. 24.1%, P = 0.046; 34.6% vs. 7.4%, P = 0.002). The 5-year survival rate of patients with ECS was significantly lower than that of patients without ECS (23.1% vs. 57.4%, P = 0.013).</p><p><b>CONCLUSION</b>ECS is an important prognostic factor in laryngeal cancer. Patients with ECS have a higher incidence of contralateral neck metastasis, so bilateral neck dissection should be selected.</p>

Prognostic factors identified by Cox multivariate analysis of surgically treated 1018 laryngeal cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the prognostic factors of 1018 patients with laryngeal cancer treated surgically.</p><p><b>METHODS</b>All patients were treated surgically for laryngeal cancer from 1984 to 1996. A total of 16 clinical factors was studied by univariate analysis and Cox multivariate model.</p><p><b>RESULTS</b>The follow-up rate was 93.5% over 5 years. The overall cumulative survival rate was 79.1% at 3 years, 70.2% at 5 years. The 5-year survival rate of T1N0 is the highest, followed by T1N+, T2N0, T3N0, T4N0, T2N+, T4N+, and T3N+. In univariate analysis, the survival was related to patient age, mobility of vocal cords, preoperative T status, preoperative N status, preoperative UICC stage, postoperative T status, postoperative N status, postoperative UICC stage, topographic location of the tumor and tumor size. In Cox multivariate modal, only postoperative N status, mobility of vocal cords and tumor size were independent prognostic factors.</p><p><b>CONCLUSION</b>Independent prognostic factors for patients with laryngeal cancer after curative resection are postoperative N stage, mobility of vocal cords as well as tumor size. Postoperative follow-up and salvage surgery in time should be attached with importance to improve the survival of patients with laryngeal cancer.</p>

Missing diagnosis of neck metastases by routine detecting method in laryngeal carcinomas / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the missing diagnosis of neck metastases by routine detecting method (palpation combined with one pathological slide) in laryngeal carcinomas.</p><p><b>METHODS</b>Sixty-six specimens of neck dissections were collected and observed by routine method, transparent method, and continuous sliding method.</p><p><b>RESULTS</b>Totally, 1153 lymph nodes were detected by palpation method and another 1204 lymph nodes were detected by transparent method. The lymph nodes detected by transparent method account for 51.1% of the total, and among them 10 metastases were found, which account for 15.6% (10/64) of metastatic lymph nodes. For those with no metastasis detected by routine method, 50 microm interval continuous sliding method was performed, and 14 tiny metastases were found, which account for 21.9% (14/64) of metastatic lymph nodes. Detecting by routine method, most lymph nodes (95%) were in tumor growth and tumor suffusion stage. The missing diagnosis rate of routine method was 37.5% (24/64).</p><p><b>CONCLUSIONS</b>When routine method was used to detect lymph nodes in neck specimens, missing diagnosis should be considered to select best therapy. Through transparent method small lymph nodes could be found and it is a valuable method to observe pathological changes of small nodes. Continuous sliding method could find micrometastasis precisely, but the work burden is heavy and it is difficult to be widely used.</p>

Impact of extracapsular lymph node spread in the ipsilateral neck on contralateral neck metastasis and prognosis of laryngeal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the impact of extracapsular lymph node spread (ECS) in the ipsilateral neck on the contralateral neck metastasis and prognosis of laryngeal cancer.</p><p><b>METHODS</b>The data of 184 laryngeal cancer patients who underwent laryngectomy and simultaneous radical or modified radical neck lymph node dissection between Jan. 1994 and Dec. 1997 were retrospectively analyzed. Of these 184 patients, 144 underwent unilateral neck lymph node dissection and 40 bilateral; 159 had supraglottic lesion and 25 transglottic. All had squamous cell carcinoma. The clinical T stage was T1 in 3, T2 63, T3 77, T4 41; N stage: NO in 123, N1 38, N2a 5, N2b 11, N2c 7. Transparent lymph node detection and continuous sectioning method were applied to all dissected neck lymph nodes. Statistical analysis was carried out using SPSS software package ( version 11.5). Survival curves were calculated through the Kaplan-Meier model. Impact of extracapsular lymph node spread in the ipsilateral neck on prognosis was assessed using the Log rank test.</p><p><b>RESULTS</b>Of these 184 patients, neck lymph node metastasis was pathologically proven in 80, 26 had ECS in the ipsilateral neck with a ECS rate of 32.5% (26/80). The ECS incidence was positively correlated with advanced pathological N stage and metastatic lymph nodes (P < 0.01). The incidence of the contralateral neck metastasis and ipsilateral neck recurrence with ECS were higher than those without ECS, which was 46.2% versus 24.1%, and 34.6% versus 7.4%, respectively (P < 0.05). The 3- and 5-year survival rates of patients with ECS were significantly lower than those of patients without ECS, which was 53.9% versus 70.4%, and 23.1% versus 57.4%, respectively (P = 0.0125).</p><p><b>CONCLUSION</b>Extracapsular lymph node spread is found to be an important prognostic factor in the laryngeal cancer. Bilateral neck dissection may be mandatory due to patients with ECS have a higher incidence of contralateral neck metastasis. The capsule of metastatic lymph nodes should be pathologically checked and reported in order to determine the extra-capsular spread status.</p>

Reconstruction of laryngeal defect in vertical partial laryngectomy with resection of arytenoid cartilage / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To discuss the method to reconstruct laryngeal defect after vertical partial laryngectomy with resection of arytenoid cartilage.</p><p><b>METHODS</b>Laryngeal defect was reconstructed with local tissues after vertical partial laryngectomy with resection of arytenoid cartilage on 87 patients with laryngeal carcinoma of glottic type (T1 7 cases, T2 54 cases, T3 26 cases). All the lesions invaded arytenoid area or vocal process. No filling tissues were used to increase the height of affected arytenoid area and no skin flap or other tissues were used to reconstruct the vocal cord in all the patients.</p><p><b>RESULTS</b>All the patients recovered normal swallow in 8 to 19 days postoperation and restored phonation. The decannulation rate was 98.9% (86/87). There were no pharyngeal fistula and pulmonary complications after operation. Local infection occurred in 3 patients and was cured in 7 days. The rate of local recurrence and cervical lymph node metastasis were 8.0% (7/87), 6.9% (6/87) respectively. Lost patients were assumed to death and direct method was used to calculate survival rate. In 87 patients postoperative period was above 3 years, 5 died in 3 years and 3 were lost 3- year survival rate was 90.8% (79/87). In 63 patients postoperative period was above 5 years, 10 died in 5 years and 2 were lost. 5- year survival rate was 81.0% (51/63).</p><p><b>CONCLUSIONS</b>Utilizing local tissues to reconstruct laryngeal defect after vertical partial laryngectomy with resection of arytenoid cartilage will not lead to severe dysphagia. Phonation is acceptable. It not only saves the operation time but also avoids the negative effects of immoderate reparation.</p>