[Clinical analysis of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma].

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.

[The triglyceride glucose index predicts the risk of nonfatal cardio-cerebrovascular disease in the Beijing community: a prospective cohort study].

Objective: To explore the characteristics of the association between the triglyceride glucose (TyG) index and nonfatal cardio-cerebrovascular disease risk in a community population. Method: This was a prospective cohort study. From December 2011 to April 2012, the first investigation was conducted among subjects with more than 40-year old who were from Shijingshan district and Pingguoyuan community in Beijing. The second investigation was conducted from April to October 2015. All the subjects were divided into three groups according to the tertile of the TyG index at baseline. The multivariate Cox proportional risk regression model was established to explore the correlation between the TyG index and nonfatal cardio-cerebrovascular disease risk and the Kaplan-Meier survival curve of the TyG index group was drawn. Subgroup analyses were performed according to age, gender, body mass index, type 2 diabetes mellitus (T2DM), hypertension, and hyperlipidemia to determine the correlation characteristics between the TyG index and nonfatal cardio-cerebrovascular disease among subgroups. Results: A total of 9 577 subjects were finally included to analyze. The mean follow-up time of this study was (34.14±3.84) months. During the follow-up, 363 subjects (3.8%) occurred nonfatal cardio-cerebrovascular disease. The multivariate Cox regression analysis results showed that the hazard ratio (HR) of nonfatal cardio-cerebrovascular disease in the high TyG index group was 1.54 (95%CI 1.19-1.98), 1.60 (95%CI 1.23-2.10), and 1.57 (95%CI 1.20-2.05) in the three models, compared with the low TyG index group. The Kaplan-Meier analysis showed that the risk of nonfatal cardio-cerebrovascular disease increased from the low-TyG index group to the high-TyG index group (P=0.015). In the six subgroups analysis, only gender was shown to have a significant interaction effect with the TyG index and nonfatal cardio-cerebrovascular disease risk. In the female population, the risk of nonfatal cardio-cerebrovascular disease is significantly increased with the increase in the TyG index level (P<0.001). Conclusions: A high TyG index is independently related to the increased risk of nonfatal cardio-cerebrovascular disease in the Beijing community population. Gender has a significant interaction with the TyG index and nonfatal cardio-cerebrovascular disease risk. Therefore, the TyG index may be a useful marker to predict the nonfatal cardio-cerebrovascular disease risk of a community population.

[Correlation analysis of anterior pituitary hormone and tumor size in patients with pituitary adenomas].

Objective: To summarize the correlation between anterior pituitary function and tumor size in patients with different hormone-secreting pituitary adenomas. Methods: This was a retrospective case series study. The clinical data of 1 946 patients with pituitary adenoma hospitalized in the First Medical Center of Chinese PLA General Hospital from January 1, 2005, to December 31, 2020, were collected. The correlation between tumor size and anterior pituitary hormone levels was analyzed using Spearman rank correlation analysis in different types of pituitary adenomas. Results: The median age of the 1 946 patients was 45.1 years, of which 857 (44.0%) were men. The maximum tumor diameter of the patients [M (Q1, Q3)] was 22 (14, 30) mm. Tumor size in nonfunctioning adenomas (n=1 191) was negatively correlated with adrenocorticotropic hormone (ACTH) (r=-0.11, P<0.001), growth hormone (r=-0.13, P<0.001), and luteinizing hormone (men: r=-0.26, P<0.001, women: r=-0.31, all P<0.001). The tumor size of somatotropic adenomas (n=297) was positively correlated with growth hormone (r=0.46, P<0.001), but negatively correlated with male testosterone (r=-0.41, P<0.001). The tumor size of ACTH-secreting pituitary adenomas (n=155) was positively correlated with the ACTH level at 8∶00 AM (r=0.25, P<0.001); however, no correlation was found with cortisol at 8∶00 AM (P>0.05). The tumor size of prolactinomas (n=303) was positively correlated with the prolactin level (men: r=0.34, P=0.001; women: r=0.13, P=0.070). Conclusions: The correlation between the function of the anterior pituitary and size of the tumor depends on the cellular origin of the pituitary adenoma and specific type of hormone secretion. In somatotroph adenomas, ACTH-secreting pituitary adenomas, and prolactinomas, there is a positive correlation between tumor size and level of hormones secreted by the corresponding tumors. In patients with nonfunctioning adenomas, the tumor size was negatively correlated with the hormone levels of the pituitary-adrenal and pituitary-growth hormone axes.

[Research progress of FAPI PET/CT in the diagnosis of malignant liver tumors].

Malignant liver tumors have a high incidence and mortality rate. Therefore, it is of great significance to promptly learn about tumor advancement status through relevant examinations for patients' follow-up, diagnosis, and therapy as well as the improvement of the five-year survival rate. The primary lesions and intrahepatic metastases of malignant liver tumors have been better demonstrated in the clinical study with the use of various isotope-labeled fibroblast activating protein inhibitors because of their low uptake in liver tissues and high tumor/background ratio, which provides a new method for early diagnosis, precise staging, and radionuclide therapy. In light of this context, a review of the research progress of fibroblast-activating protein inhibitors for the diagnosis of liver malignant tumors is presented.

[Efficacy of surgical comprehensive therapy for 456 cases of hypopharyngeal carcinoma].

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.

[Study on nomograph predicting the risk of type 2 diabetes mellitus in Beijing community adults].

Objective: Development and validation of a nomogram for predicting the 4-year incidence of type-2 diabetes mellitus (T2DM) in a Chinese population was attempted. Methods: This prospective cohort study was conducted in Shijingshan District Pingguoyuan Community (Beijing, China) from December 2011 to April 2012 among adults aged≥40 years not suffering from T2DM. Finally, 8 058 adults free of T2DM were included with a median duration of follow-up of 4 years. Participants were divided into a modeling group and verification group using simple random sampling at a ratio of 7∶3. Univariate and multivariate Cox proportional risk models were applied to identify the independent risk predictors in the modeling group. A nomogram was constructed to predict the 4-year incidence of T2DM based on the results of multivariate analysis. The Concordance Index and calibration plots were used to evaluate the differentiation and calibration of the nomogram in both groups. Results: A total of 5 641 individuals were in the modeling group and 2 417 people were in the validation group, of which 265 and 106 had T2DM, respectively, at 4-year follow-up. In the modeling group, age (HR=1.349, 95%CI 1.011-1.800), body mass index (HR=1.347, 95%CI 1.038-1.746), hyperlipidemia (HR=1.504, 95%CI 1.133-1.996), fasting blood glucose (HR=4.189, 95%CI 3.010-5.830), 2-h blood glucose level according to the oral glucose tolerance test (HR=3.005, 95%CI 2.129-4.241), level of glycosylated hemoglobin (HR=3.162, 95%CI 2.283-4.380), and level of γ-glutamyl transferase (HR=1.920, 95%CI 1.385-2.661) were independent risk factors for T2DM. Validation of the nomogram revealed the Concordance Index of the modeling group and validation group to be 0.906 (95%CI 0.888-0.925) and 0.844 (95%CI 0.796-0.892), respectively. Calibration plots showed good calibration in both groups. Conclusion: These data suggest that our nomogram could be a simple and reliable tool for predicting the 4-year risk of developing T2DM in a high-risk Chinese population.

[Mechanism of pepsin promoting lingual tonsil hypertrophy by stimulating macrophage].

Objective: To investigate the possible pathophysiological mechanism of laryngopharyngeal reflux (LPR) in the development of lingual tonsil hypertrophy (LTH). Methods: The lingual tonsil tissues were collected from 73 patients [48 males and 25 females, aged from 24 to 76 (52.86±12.04) years] who underwent surgery for laryngopharyngeal diseases at the Department of Otolaryngology and Head and Neck Surgery, Southern Hospital of Southern Medical University from October 2019 to December 2020, and the lingual tonsil grade (LTG), reflux symptom index (RSI) and reflux finding score (RFS) were assessed. The expression of pepsin in LTH was detected by immunohistochemistry. The coexpression of pepsin and macrophages were detected by immunohistofluorescence. In vitro, cytological experiments and pathway assays were performed on macrophages stimulated by pepsin. Pathway alterations of macrophages in pepsin-positive high-grade LTH were detected by double-fluorescence immunohistochemistry. Data were analyzed by SPSS 20.0 software. Results: There were 44 clinically significant LPRD patients with LTG 3 and 4, and the pepsin positive rate was 88.6% (39/44). While, the pepsin positive rate of LTG 1 and 2 was 48.3% (14/29). LTG was significantly positively correlated with RFS/RSI positive rate(χ2=23.01/19.62, P<0.001/0.001; r=0.54/0.51, P<0.001/0.001) and pepsin tissue staining intensity (H=21.58, P<0.001; r=0.53, P<0.001), respectively. Pepsin and macrophages were clearly colocalized in high grade LTH. In vitro, pepsin promoted macrophage proliferation (P<0.05) and production of IL-6/IL-8 (P<0.05). Pepsin significantly up-regulated the p38/JNK MAPK pathway in macrophages (P<0.05). Pepsin up-regulated the expression of IL-6 and IL-8 of macrophages by activating the p38 MAPK pathway (P<0.05), and up-regulated the expression of IL-8 by activating the JNK pathway (P<0.05). The p38/JNK MAPK pathways were highly expressed in macrophages of pepsin-positive LTH (P<0.05). Conclusions: LPR is an important pathogenic factor in LTH. Macrophages may mediate pepsin-induced inflammation and the pathogenesis of LTH.

[The effect of cervical lymph node metastasis density on prognosis of hypopharyngeal carcinoma].

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 (χ2=9.31, 7.30, 20.09, 15.30, 9.04, 19.44, 50.27, all P values<0.05) and OS (χ2 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.

[Clinical features and prognostic influences of retropharyngeal lymph node metastasis in oropharyngeal and hypopharyngeal squamous cell carcinoma: a meta analysis].

Objective: To compare the clinical features and prognoses of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) with and without retropharyngeal lymph node metastases. Methods: PubMed, Cochrane, Web of Science, CNKI, VIP and Wanfang databases were searched for published literatures on retropharyngeal lymph node metastasis of oropharyngeal or hypopharyngeal squamous cell carcinoma (1900, 2021), and outcome indicators such as survival rate and related clinical features were extracted. The quality evaluation of the included literatures was carried out. RevMan 5.4 and Stata 16.0 software were used for data analysis. Results: A total of 18 literatures were included. Meta analysis showed that 3-year and 5-year survival rates and 5-year disease-specific survival rate of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma with retropharyngeal lymph node metastases were lower than those without metastases, 46.1% vs. 53.0%, 40.8% vs. 62.5% and 35.9% vs. 53.1%, respectively, and the differences were statistically significant (OR values were 0.26, 0.38, 0.38, and 95%CI were 0.10-0.69, 0.28-0.51, 0.23-0.65, respectively, all P values<0.05). There were statistically significant differences in clinical stage (III-IV), T stage (T3+T4), N stage (N2), positive cervical lymph node metastases and number of lymph node metastases (≥3) between the two groups (OR values were 4.28, 2.20, 2.88, 10.83, 6.53, and 95%CI were 1.70-10.74, 1.35-3.58, 1.90-4.34, 3.57-32.95, 1.75-24.38, respectively, all P<0.05). The sensitivity and specificity of preoperative imaging for diagnosing retropharyngeal lymph nodes metastases were respectively 0.72 (95%CI=0.54-0.85) and 0.98 (95%CI=0.74-1.00), and the area under curve (AUC) of summary receiver operating characteristic curve (SROC) was 0.84 (95%CI=0.80-0.87). Conclusions: The survival rate of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma with retropharyngeal lymph node metastasis is significantly reduced, the clinical stage and T stage are late, and the cervical lymph node metastasis rate is high. Retropharyngeal lymph node metastasis is more insidious, the sensitivity of preoperative imaging diagnosis is not high.

[Diagnosis and treatment of 21-hydroxylase deficiency with testicular adrenal rest tumors:a report of three cases and literature review].

Objective: To provide insight into the diagnosis for clinicians, the clinical characteristics, diagnosis and treatment history of 3 patients with 21-hydroxylase deficiency (21-OHD) and testicular adrenal rest tumors (TART) were analyzed. Methods: The clinical, laboratory and imaging data of 3 male patients with 21-OHD and TART, confirmed with CYP21 gene sequencing, from May 2010 to May 2021 in the First Medical Center of Chinese PLA General Hospital were analyzed retrospectively. The treatment strategy and clinical outcome were followed up. Results: All the 3 patients were first diagnosed with bilateral adrenal mass at the age of 27-42 years old. They were 145-162 cm tall. The levels of progesterone, 17-hydroxyprogesterone, and adrenocorticotropic hormone (ACTH) of the 3 patients were relatively high, and that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) of the 3 patients were low. Testosterone level of 1 patient was significantly elevated, and that of the other 2 patients was below the lower limit of normal range. Testicular ultrasound showed heterogeneous hyperechoic masses in both testes. CT of the adrenal glands showed bilateral adrenal enlargement with mass. All 3 patients were treated with dexamethasone. After 4-96 months of follow-up, 17-hydroxyprogesterone level was kept above the median normal level. One of the patients got married and had a baby after treatment. The sizes of adrenal hyperplasia and testicular masses reduced to various degrees with the change of the testicular masses being proportional to that of adrenal hyperplasia. Conclusions: Patients with 21-OHD are prone to have TART, leading to the impaired testicular function. Early glucocorticold therapy is beneficial to the reduction of TART and restoration of testicular function.

[Clinical aspects of pregnancy-related lymphocytic hypophysitis].

Objective: To analyze clinical features, diagnosis, treatment and prognosis of pregnancy-related lymphocytic hypophysitis (LyH). Methods: The clinical data of 16 cases diagnosed as pregnancy-related LyH at Chinese PLA General Hospital between October 2010 and November 2019 were reviewed. Results: Sixteen patients were included (aged 20-40 years). All patients' symptoms occurred from the last 2 months of pregnancy to 12 months postpartum, with 6 cases in the third trimester and 10 cases during postpartum, and all the patients were diagnosed after delivery. Six patients had lymphocytic adenohypophysitis (LAH), 4 patients had lymphocytic infundibuloneurohypophysitis (LINH), 4 patients had lymphocytic panhypophysitis (LPH), and 2 had lymphocytic hypothalamitis. Eight patients presented with symptoms of intracranial space-occupying lesions, 14 patients had symptoms of anteriorpituitary hormone deficiencies, 9 patients had central diabetes insipidus (CDI), and 2 had hyperprolactinemia. Pituitary MRI showed that the pituitary presented with diffuse enlargement, pituitary stalk thickening, disappearing of high-intensity signals in posterior pituitary and space-occupying lesions in the infundibulum of hypothalamus. Nine patients were treated with immunosuppressive agent, 3 patients alleviated the space-occupying effects after surgery, and 4 patients recovered spontaneously. Fourteen patients were followed up with a period of 3-98 months. Four patients had a relapse, 2 patients had a complete remission, and 12 patients needed long-term hormone replacement therapy. Conclusions: Clinical manifestations of pregnancy-related LyH are diverse. LyH should be suspected in pregnant or postpartum women with a sellar mass to avoid missed diagnosis or misdiagnosis. Immunosuppressant therapy is effective. Overall, LyH patients have a favorable prognosis.