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Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx ( OR =4.83, 95% CI: 1.27-18.40), N2 stage ( OR =6.30, 95% CI: 2.25-17.67), and N3 stage ( OR =26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR =1.28, 95% CI: 1.06-1.54; N stage: HR =1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR =2.13, 95% CI: 1.47-3.08; radiotherapy: HR =0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR =1.26, 95% CI: 1.06-1.51; N stage: HR =1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR =2.24, 95% CI: 1.56-3.21; radiotherapy: HR =0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.

Objective: To retrospectively analyse the efficacy of surgerical comprehensive treatment for hypopharyngeal cancer. Methods: Four hundred and fifty-six cases of hypopharyngeal squamous cell carcinoma treated from Jan 2014 to Dec 2019 were analyzed retrospectively, including 432 males and 24 females, aged 37-82 years old. There were 328 cases of pyriform sinus carcinoma, 88 cases of posterior pharyngeal wall carcinoma, and 40 cases of postcricoid carcinoma. According to American Joint Committe on Cancer(AJCC) 2018 criteria, 420 cases were of stage Ⅲ or Ⅳ; 325 cases were of T3 or T4 stage. Treatment methods included surgery alone in 84 cases, preoperative planned radiotherapy plus surgery in 49 cases, surgery plus adjuvant radiotherapy or concurrent chemoradiotherapy in 314 cases, and inductive chemotherapy plus surgery and adjuvant radiotherapy in 9 cases. The primary tumor resection methods included transoral laser surgery in 5 cases, partial laryngopharyngectomy in 74 cases, of them 48 cases (64.9%) presented with supracricoid hemilaryngopharyngectomy, total laryngectomy with patial pharyngectomy in 90 cases, total laryngopharyngectomy or with cervical esophagectomy in 226 cases, and total laryngopharyngectomy with total esophagectomy in 61 cases. Among 456 cases, 226 cases received reconstruction surgery with free jejunum transplantation, 61 cases with gastric pull-up, and 32 cases with pectoralis myocutaneous flaps. All patients underwent retropharyngeal lymph node dissection, and high-definition gastroscopy was performed during admission and follow-up. SPSS 24.0 software was used to analyze the data. Results: The 3-year and 5-year overall survival rates were respectively 59.8%, and 49.5%. The 3-year and 5-year disease specific survival rates were respectively 69.0% and 58.8%. Total metastasis rate of retropharyngeal lymph nodes was 12.7%. A total of 132 patients (28.9%) suffered from simultaneous and metachronous multiple primary carcinoma of the hypopharynx. Multivariate Logistic regression analysis showed that T3-4 disease, cervical lymph node metastasis, retropharyngeal lymph node metastasis and postoperative adjuvant radiotherapy were independent factors affecting the prognosis of patients (all P <0.05). As of April 30, 2022, a total of 221 patients died during follow-up, of 109 (49.3%) with distant metastases, which were the main cause of death. Conclusions: The efficacy of comprehensive treatment for hypopharyngeal cancer can be improved by accurate preoperative evaluation, improved surgical resection, active retropharyngeal lymph node dissection and full process intervention of the second primary cancer.

Objective: To investigate the relationship between the cervical lymph node density (LND) and the prognosis of hypopharyngeal carcinoma. Methods: The clinical and pathological data of 241 patients with hypopharyngeal carcinoma who underwent surgery in Shandong Provincial ENT Hospital from January 2014 to December 2017 were retrospectively analyzed, including 229 males and 12 females, aged 37-81 years. The LND was calculated, i.e. the ratio of the number of lymph nodes with metastasis to the total number of lymph nodes removed. The patients were divided into low LND group and high LND group based on the cutoff value of LND determined by receiver operating characteristic curve (ROC curve). The univariate and multivariate analyses of the disease-free survival (DFS) and the overall survival (OS) were performed in two groups. Results: With the cutoff value of 0.068, 165 patients were in the low LND group (<0.068) and 76 patients in the high LND group (≥0.068). T stage, N stage, maximum lymph node diameter, extracellular invasion of lymph node, and postpharyngeal lymph node metastasis were associated with LND (statistical values were -3.15, -6.82, 23.37, 20.44, and 30.18, respectively, all P values were<0.05). The univariate analysis showed that age, T stage, N stage, maximum diameter of cervical lymph nodes, extracapsular invasion, retropharyngeal lymph node metastasis and LND were the main factors affecting the patients' DFS (χ 2 =9.31, 7.30, 20.09, 15.30, 9.04, 19.44, 50.27, all P values<0.05) and OS (χ 2 were 5.02, 12.94, 18.28, 15.91, 7.95, 16.88, 49.45, all P values<0.05). Multivariate analysis showed that patients with age≤60 years old and LND≥0.068 had reduced DFS [ HR values were 0.61 (95% CI 0.43-0.88) and 2.23 (95% CI 1.44-3.45), both P values<0.05]; patients with advanced T stage and LND≥0.068 had reduced OS [ HR values were 1.73 (95% CI 1.02-2.93) and 2.39 (95% CI 1.51-3.80), both P values<0.05]. Conclusion: LND is a prognostic factor for patients with hypopharyngeal carcinoma after surgery, with worse prognosis in patients with LND≥0.068.

Objective: To evaluate the oncologic and functional outcomes of laryngeal squamous cell carcinomas treated by supracricoid laryngectomy. Methods: The clinical data of 134 patients with laryngeal cancer who underwent supracricoid laryngectomy with cricohyoidoepiglottopexy (CHEP) or cricohyoidopexy (CHP) between July 2005 and April 2014 at Shandong Provincial ENT Hospital were retrospectively reviewed. Ninety-one patients including 31 cases of stage Ⅰ, 36 of stage Ⅱ, 18 of stage Ⅲ and 6 of stage Ⅳ underwent CHEP and 43 patients underwent CHP. Two patients received CHEP due to recurrence after open surgery and laser surgery. Three patients received CHP due to the recurrence of disease after open surgery and postradiotherapy persistence of disease. The Kaplan-Meier method was used to calculate the 3-year and 5-year survival rates. The Chi-square test was used to compare the survival rates between different surgical procedures. Results: All 91 patients who underwent CHEP had successful removals of PEG tubes, and 88 (96.7%) of them had tracheostomy tube decannulation. Among 43 patients with CHP, 42(97.6%) cases removal of PEG tubes(97.6%), including and 40(93.0%) cases with tracheostomy tube decannulation. There was one patient with local recurrence in all cases. In CHEP group, 3-year local control rate was 98.2%; 3-year and 5-year overall survival rate were 94.5% and 93.9%, respectively. In CHP group, 3-year local control rate was 97.6%; 3-year and 5-year overall survival rates were 86.0% and 83.3%, respectively. Pharyngeal fistula appeared in 2 cases of CHEP group and 4 cases of CHP group, and all of them were cured by conservative treatment. Conclusion: Supracricoid laryngectomy shows excellent oncologic and functional results for treatment of laryngeal cancer while maintaining laryngeal functions, especially in terms of local control rate and tracheostomy tube decannulation.

Objective: investigate the incidence of retropharyngeal lymph node (RPLN) metastasis and the risk factors for RPLN metastasis in hypopharyngeal cancer, and the relationship of planned dissection of the RPLN with the survival and tumor control rates in patients with hypopharyngeal cancer. Methods: A total of 203 patients with hypopharyngeal squamous cell carcinoma who underwent radical surgery as initial treatment from February 2011 to July 2015 were analyzed retrospectively. There were 167 cases of pyriform sinus carcinoma, 23 cases of posterior pharyngeal wall carcinoma, and 13 cases of postcricoid carcinoma. Results: The incidence of RPLN metastasis in HPC was 17.7%, with a highest rate of 43.5% in pharyngeal wall carcinoma. The incidence of RPLN metastasis in T3-4 pyriform sinus carcinoma was 18.3%, which significantly higher than 2.8% in T1-2 cases(χ(2)=5.360, P =0.020). The rate of RPLN metastasis was 23.8% in N2b-3 and 8.6% in N0-2a, with a statistically significant difference(χ(2)=7.637, P =0.006). There was no statistically significant difference in overall survival rates between patients with and without RPLN metastasis( P >0.05). Data were analyzed by SPSS 13.0 software. Conclusions: RPLN metastasis is not rare in hypopharyngeal carcinoma. Planned dissection of the RPLN should be performed with the initial surgery in patients with advanced hypopharyngeal cancer, especially posterior pharyngeal wall carcinoma, T3-4 pyriform sinus carcinoma and staged N2b-3 disease, which can reduce the regional recurrence rate and provided with a better prognosis.

Objective: To investigate the key factors influencing the prognosis of hypopharyngeal carcinoma and the therapeutic methods improving the efficacy of treatments for hypopharyngeal carcinoma. Methods: Two hundred and sixty-four cases of hypopharyngeal squamous cell carcinoma treated from May 2010 to May 2015 were analyzed retrospectively. There were 211 cases of pyriform sinus carcinoma, 37 cases of posterior pharyngeal wall carcinoma, and 16 cases of postcricoid carcinoma. According to UICC 2002 criteria, 2 cases were for stage Ⅰ, 14 for stage Ⅱ, 32 for stage Ⅲ and 216 for stage Ⅳ. Postoperative circumferential defects existed in 112 (42.4%) cases, and 86 of them were reconstructed with free jejunum transplantation. Among all cases, 54 patients (20.5%) had the preservation of laryngeal functions after surgery and 210 patients (79.5%) with total laryngectomy; 238 cases (90.2%) underwent bilateral cervical lymph node dissection and 203 patients received posterior pharyngeal lymph node exploration and dissection, with positive metastases for posterior pharyngeal lymph nodes in 36 cases (17.7%). Eight cases with cervical lymph node metastasis extensively involving the soft tissue, prevertebral fascia or encases carotid artery received preoperative radiotherapy of 50 Gy. After surgery 13 patients received concurrent radiotherapy and chemotherapy, 337 underwent adjuvant radiotherapy with a dose of 50-60 Gy each, and 14 patients did not receive radiotherapy or did not completed their radiotherapy programs. SPSS 13.0 saftware was used to analyze the data. Results: All patients were followed up for more than 2 years. With Kaplan-Meier method, the 2-, 3- and 5-years survival rates were 69.6%, 62.8% and 51.3%, respectively. There were significant differences in 3-year survival rates between T1-2 group (75.5%) and T3-4 group (59.2%) (χ(2)=4.282 P =0.039), N0 group (81.6%) and N+ group (58.2%) (χ(2)=6.802 P =0.009), laryngeal functions preserved (81.8%) and unpreserved group (58.9%) (χ(2)=5.314 P =0.021). Multivariate Logistic regression analysis showed that cervical lymph node metastasis was an independent prognostic factor ( P =0.027). The success rate of free jejunum transplantation was 98.8%. Local recurrence, cervical lymph node recurrence, second primary cancer, and distant metastasis accounted respectively for 11.2%, 18.8%, 12.5% and 45.0% of death cases. Conclusions: The prognosis-associated factors for hypopharyngeal carcinoma should be taken into account, including the evaluation of the carcinogenesis of the mucosal area, early screening of premalignant lesion or second primary cancer in the esophagus and dissection of the posterior pharyngeal lymph nodes, which will help to improve the local control rate and recent survival rate in patients with hypopharyngeal cancer.

Objective: To evaluate the usefullness of flexible esophagoscopy and chromoendoscopy with Lugol's solution in the detection of synchronous esophageal neoplasm in patients with hypopharyngeal squamous cell carcinoma (HSCC). Methods: A retrospective review of 96 cases with HSCC that received surgical treatment from March 2016 to March 2017 was accomplished. In these patients, the site of origin were pyriform sinus ( n =75), posterior pharyngeal wall ( n =11) and postcricoid ( n =10). Esophagoscopy was prospectively performed on all patients before treatment for HSCC. All patients underwent conventional white-light endoscopic examination with Lugol chromoendoscopy and narrow band image. Suspicious areas of narrow band image or Lugol-voiding lesions were observed and biopsied. The treatment strategy of primary HSCC was modified according to the presence of synchronous esophageal squamous cell neoplasms by a multidisciplinary approach. Results: Ninety-six patients were enrolled (age ranging from 37-80 years). All patients did not have previous treatment.Histopathological analysis revealed middle to high-grade dysplasia in 5 cases, Tis cancer in 5 cases, cancer in 16 cases and inflammation or normal findings in the others. Four cases were treated with endoscopic submucosal dissection before hypopharygeal surgery, 3 cases with lower esophageal cancers were treated with gastric pull-up combined with free jejunal flap after total circumferential pharyngolaryngectomy (TCPL) and certical esophagectomy, and 14 cases were treated with TCPL, total esophagectomy and gastric pull-up. Conclusions: Esophagoscopy is a feasible and justified procedure in HSCC cases as it enhances the detection of premalignant lesion or second primary cancer. Routine esophagoscopy for detecting synchronous second primary tumor should be recommended for patients with HSCC. The treatment strategy for primary HSCC is modified according to the presence of synchronous second primary tumor.

In lung cancer, antiangiogenic treatment targeting tumor endothelial cells (ECs) provides a survival advantage. To fully elucidate the behavior of ECs in a tumor microenvironment, high-purity (>98%) normal, paratumor-, and tumor-derived CD105(+) ECs were purified from lung squamous cell carcinoma by incubating cells with anti-CD105 antibody-coated magnetic beads. These cells exhibited typical EC characteristics. Totally, 1765 proteins were identified with high confidence by isobaric stable isotope tags and two-dimensional LC/MS/MS (iTRAQ-2DLC/MS/MS). In particular, 178 and 162 proteins were differentially expressed in paratumor- and tumor-derived ECs, respectively, compared to normal ECs. The up- and down-regulation trends showed good interassay correlation. Using gene ontology, they were classified into genes involved in major reprogramming of cellular metabolic processes, oxidative stress response, redox homeostasis, apoptosis, and platelet degranulation/activation. Moreover, tumor angiogenesis-initiating ECs appeared to acquire distinct properties. For example, cell migration and regulation of smooth muscle cell migration of paratumor-derived ECs were significantly faster than that of normal and tumor-derived ECs. Among them, two migration-associated proteins, neuropilin 1 and platelet-derived growth factor receptor β predominantly expressed in ECs of paratumor from 16 patients with lung squamous cell carcinoma, were identified as potential biomarkers for antiangiogenic therapy.

Objective: To investigate the efficacy of surgery followed by adjuvant radiotherapy and the prognostic factors affecting the results of treatment in hypopharyngeal carcinoma., Methods: A retrospective review of 149 patients with hypopharyngeal carcinoma that received surgical treatment from Jun 2003 to Jun 2010 was accomplished. In the 149 patients, the site of origin were pyriform sinus (n = 121), posterior pharyngeal wall (n = 21) and postcricoid (n = 7). According to UICC 2002 criteria, there were 3 in stage I, 15 in stage II, 29 in stage III and 102 in stage IV. Surgical methods for primary tumor were: pyriform sinus resection or posterior pharyngeal wall resection in 22 cases, partial pharyngectomy and partial laryngectomy in 29 cases, partial pharyngectomy and total laryngectomy in 67 cases, total pharyngectomy and total laryngectomy in 16 cases, total pharyngolaryngectomy and partial esophagus resection in 12 cases, and total esophagus resection in 3 cases. All the patients received elective and/or radical neck dissection. Unilateral or bilateral thyroid lobectomy was performed in 98 cases. Eighty-seven patients received intensity modulation radiated therapy (IMRT) postoperatively in the cancer center of Provincial Hospital Affiliated to Shandong University. Individualized adjustment of the radiation field was made according to the surgical condition. Forty-nine cases received radiotherapy in other hospitals (dose 50-70 Gy). Laryngeal function was restored in 51 patients (34.2%). The risk clinicopathological factors of survival and the causes of death were analyzed., Results: The survival rate was calculated with Kaplan-Meier method. The overall 3- and 5- year survival rates were 47.7% and 38.7%, respectively. There were no significant differences in 3-year survival between T1-2 and T3-4 groups, N0 and N+ groups, stage I-II and III-IV groups, laryngeal function preserved and unpreserved groups. The overall 3 years survival rate of patients received surgery and adjuvant radiotherapy was higher than those just received surgery alone (χ² = 6.851, P < 0.05). The 3-year survival rate in patients treated in comprehensive treatment group has showed a good trend, although still no statistical significance (χ² = 0.176, P > 0.05). The cause of death in 86 patients, including regional lymph nodes recurrence in 25 cases (29.1%). Of them, one was stoma recurrence and 9 were retropharyngeal lymph nodes metastasis; distant metastasis in 19 cases (22.1%); local recurrence in 13 cases, local or regional recurrence with distant metastasis in 8 cases (9.3%), and second primary cancer in 6 cases (7.0%)., Conclusions: The overall prognosis of hypopharyngeal carcinoma was poor and dismal. In accordance with specific conditions of surgery, active adjustment of the personalized protocol of IMRT was the key of improving the efficacy of hypopharyngeal carcinoma.

Objective: To investigate the necessity and feasibility of planned dissection of the retropharyngeal lymph nodes (RPLN) in advanced hypopharyngeal cancer., Methods: Between February 2011 and December 2012, 54 patients with advanced hypopharyngeal cancer accepted planned dissection of the RPLN during primary surgery. There were 45 cases of pyriform sinus carcinoma, 5 cases of posterior pharyngeal wall carcinoma, and 4 cases of postcricoid carcinoma. All patients underwent surgery and postoperative adjuvant radiotherapy, meanwhile bilateral neck dissection and RPLN dissection were performed. All patients received preoperative CT scanning (with contrast). The results of the radiographic assessment were compared with the postoperative pathologic findings respectively., Results: RPLN were confirmed positive by pathology in 13 cases, and negative in another 43 cases. For the entire treatment group, metastasis to the RPLN was confirmed hispathologically in 12 patients (22.2%). Eight patients were pyriform sinus carcinoma, 4 were posterior pharyngeal wall carcinoma. Among them, seven patients were diagnosed as RPLN metastasis by CT imaging and another 5 patients were not confirmed. The overall accuracy for the radiologist's interpretation was 79.6%, the sensitivity was 58.3%, and the specificity was found to be 85.7%. Eleven patients were N2-3 and 6 patients were N2c. No RPLN metastasis or recurrence was found during more than one year follow-up period., Conclusions: It is not rare for the RPLN metastasis in patients with advanced hypopharyngeal carcinoma. CT imaging is not effective in determining the early presence of RPLN metastasis. The planned dissection of the RPLN is highly recommended during the initial surgery of hypopharyngeal cancer, especially in posterior pharyngeal wall carcinoma, T3-4 pyriform sinus carcinoma and staged N2-3 cases.