[Surgical treatment of papillary thyroid carcinoma involving larynx and trachea].

Objective: To evaluate the efficacy of surgical treatment of papillary thyroid carcinoma (PTC) involving larynx and trachea. Methods: A total of 1 436 cases of thyroid malignant tumors were admitted to the Department of Otolaryngology, Qilu Hospital of Shandong University from 2004 to 2019, including 110 cases of PTC involving larynx and trachea, and of which 105 cases with complete follow-up data were retrospectively analyzed. There were 42 males and 63 females, with a male/female ratio of 1∶1.5, aged from 28 to 81 years. All lesions involved trachea, including 11 cases involving both trachea and larynx. Of those 83 cases underwent laryngeal and airway wall tumor excision, and 22 cases underwent radical tumor excision plus laryngeal and trachea repair. Extubation rate was analyzed and the postoperative survival curve of patients was analyzed by Kaplan-Meier method. Results: Among 105 cases, 16 cases underwent tracheotomy and 12 cases were successfully extubated. The overall 3- 5- and 10-year survival rates were 100.0%, 86.4% and 72.5%, and the disease-free survival rates were 93.1%, 81.6% and 57.7%, respectively. There was significant difference in survival curve between the two groups (χ2=4.21, P=0.040). The 5-year and 10-year survival rates were 94.6% and 77.3% in laryngeal and tracheal tumor exclusion group, and 85.7% and 51.4% in the radical tumor resection group. There was no significant difference in the survival curves between the two groups (χ2=3.50, P=0.061). Conclusion: PTC patients with laryngeal and tracheal involvement can achieve long survival and good quality of life through reasonable surgical treatment.

[Implication of enhanced recovery after surgery in the surgical management of hypopharyngeal squamous cell carcinoma].

Objective: To investigate the safety and efficacy of enhanced recovery after surgery (ERAS) in the clinical management of hypopharyngeal squamous cell carcinoma (HSCC). Methods: In this retrospective study, a total of 168 patients with pyriform sinus carcinoma in Qilu Hospital of Shandong University from January 2015 to January 2019 were divided into two groups, based on the different perioperative interventions that patients received, i.e. the ERAS group (n=64) and the conventional group (n=104), including 164 males and 4 females, whose ages ranged from 42 to 84 years old. The difference between two groups in the operative time, postoperative nutritional status, incidences of postoperative complications and postoperative hospitalization time were compared using the student's t test, Chi-squared test or Fisher's exact test. Results: Compared with the conventional group, patients in the ERAS group had significantly shorter operative time [(166.8±58.2) min vs. (183.3±39.9) min,t=-2.72, P=0.031], higher levels of postoperative serum albumin [(38.3±4.2) µmol/L vs. (36.6±3.3) µmol/L, t=2.73, P=0.007] and more body weight [(65.4±9.4) kg vs. (62.1±9.4) kg, t=2.22, P=0.028], lower incidences of postoperative subcutaneous infection [7.8% (5/64) vs. 20.2% (21/104), χ²=4.64, P=0.03] and severe pneumonia [4.7% (3/64) vs. 15.4% (16/104), χ²=4.52, P=0.03], and shorter postoperative hospitalization time [(16.5±3.9) d vs. (18.2±4.3) d, t=-2.65, P<0.05]. Conclusion: ERAS is effective and safe in the surgical management of HSCC, with benefits in reducing the operative stress via saving operation time, shortening the hospitalization time, ameliorating nutritional status and decreasing the incidences of complications.

[Surgical treatment of 45 patients with postcricoid carcinoma at a single institute].

Objective: To evaluate the oncologic and functional outcomes of postcricoid carcinoma treated by surgical treatment, and to summarize our clinical experience in surgical treatment and reconstructive techniques. Methods: Medical files of 45 patients were collected and retrospectively analyzed. The patients received surgical treatments between January 2010 and May 2017 in the Qilu Hospital of Shandong University, including 39 males and 6 females, the age ranged from 41 to 78 years old. T1, T2, T3 and T4 staging tumors represented respectively for 2,13,23 and 7 cases. And cervical metastasis was histologically identified in 33 cases (8 for N1 and 25 for N2). Advanced staging patients (10 in Stage Ⅲ and 30 in Stage Ⅳ) accounted for 88.9% of the cohort, while early staging cases (1 in Stage Ⅰand 4 in Stage Ⅱ) for 10.1%. All patients received cervical lymph node dissection. After tumor excision without compromising margins, hypopharyngeal functions were reconstructed by residual mucosa, pectoralis major myocutaneous flap, laryngotracheal tissue flap or gastric tissue flap, and laryngeal functions were reconstructed by epiglottis, sternohyoid myofascial flap or thyroid perichondrium. Survival rates were analyzed by the Kaplan-Meier method. Results: Postoperatively 23 patients received radiotherapy and 13 patients received chemoradiotherapy. All patients were followed up for more than 3 years. Total 3-year and 5-year survival rates were 60.5% and 49.0%, respectively. Patients obtaining the conservation of laryngeal functions accounted for 44% (20/45) of all cases. The neck lymph node positive rate was 73.3%(33/45), and log-rank test demonstrated that cervical lymph node metastasis was significantly associated with prognosis of patients (χ(2)=4.364, P=0.037). Conclusion: Appropriate surgical approaches and excision methods and comprehensive application of flaps are critical to precise tumor excision and reconstruction of laryngeal functions, thereby improving the quality of life of patients with posterior carcinoma.

[Surgical treatment in 184 patients with supraglottic carcinoma at a single institute].

Objective: To summarize clinical experience in surgical treatment of supraglottic carcinoma and reconstructive techniques. Methods: Medical files of 184 patients (173 men, 11 women) were collected and retrospectively analyzed, who underwent surgeries between January 2008 and December 2012 at Qilu Hospital of Shandong University. Among them, T1, T2, T3 and T4 staging tumors accounted respectively for 14.1% (26/184), 41.9%(77/184), 31.5%(58/184) and 12.5%(23/184). Cervical metastasis was histologically identified in 86 cases (98 for N0, 31 for N1 and 55 for N2). Advanced cases (56 cases at stage Ⅲ and 67 at stage Ⅳ), early cases (22 at stage Ⅰ and 39 at stage Ⅱ) accounted respectively for 66.8% and 33.2%. Supraglottic horizontal laryngectomy or total laryngectomy was performed to allow for tumor excision without compromising margins and the tongue flap or sternohyoidmyofascial flap was subsequently used for repairing the defect after removal of tumor. Survival rates were analyzed by the Kaplan-Meier method. Results: Patients receiving conservation laryngeal surgery accounted for 75.5% (139/184). The 3-year and 5-year survival rates for all cases were 84.2% and 70.7%, respectively. Log-rank test demonstrated that cervical lymph node metastasis, primary tumor staging and clinical TNM staging were significantly associated with prognoses of patients (P=0.003, 0.010, 0.035). Dysphagia was not observed in any case and speech function was maintained in petients with partial laryngectomy. Conclusion: Adequate pre-operative evaluation, individualized treatment, and comprehensive application of flaps for repair are critical to precise tumor excision and reconstruction of laryngeal functions.

[Comprehensive treatment of 335 patients with pyriform sinus carcinoma by surgery via the paraglottic space approach].

Objective: To report the experience in comprehensive surgical treatment of pyriform sinus carcinoma via the paraglottic space approach. Methods: Three hundred and thirty-five cases with pyriform sinus carcinoma (according to UICC 2012 criteria, stage Ⅰ, 12 cases; Ⅱ, 36; Ⅲ, 79; Ⅳ, 208; T1, 26; T2, 139; T3, 121; T4, 49; cN0, 83; cN1, 61; cN2a-b, 118; cN2c, 71; cN3, 2) treated between 2006 and 2013 were retrospectively reviewed. There were 323 males and 12 females. Age aged from 36 to 80 years old with a median of 60 years old. There was no case with distant metastasis. All patients received modified neck dissection, including unilateral in 240 patients and bilateral in 95 patients. Pharyngoesophageal defects were reconstructed with directly suture in 246 cases, pectoralis major musculocutaneous flaps in 74 cases, and laryngotracheal flaps in 15 cases. Three hundred and nineteen patients received postoperative radiotherapy (55-65 Gy). Results: The overall 3 and 5 year survival rates were 68.6% (230/335) and 52.1%(139/267), respectively. The cervical lymph node metastases were found in 265 (79.1%) patients. Pathologic findings showed that all patients had squamous cell carcinoma. Laryngeal functions (voice, respiration and deglutition) were completely restored in 277 (82.7%) patients. Conclusions: The oncological efficacy of surgery via the paraglottic space approach is sure for pyriform sinus carcinoma, especially suitable for the early and medium-term lesions. The function of the larynx can retain after surgery, with the decreased incidences of cough and pharynx fistula.

[Effect of hyperandrogenism on obstetric complications of singleton pregnancy from in vitro fertilization in women with polycystic ovary syndrome].

Objective: To compare the difference in risks of obstetric complications of singleton pregnancy between women with hyperandrogenic polycystic ovary syndrome (PCOS) and women with normoandrogenic PCOS. Methods: Prospective cohort study. This study was a secondary analysis of data collected during a multicenter randomized controlled clinical trial. Women who got clinical singleton pregnancy were grouped according to whether they were diagnosed with hyperandrogenism at baseline. There were 118 women with hyperandrogenism and 366 women without hyperandrogenism. The incidences of obstetric complications and birth weight were compared between the two groups. Results: Women with hyperandrogenic PCOS had a significantly higher risk of preterm delivery than women with normoandrogenic PCOS [12.7% (15/118) versus 3.6% (13/366); OR=3.94, 95%CI: 1.82-8.56]. After adjustment of age, duration of infertility, body mass index, and fresh or frozen embryo transfer group, hyperandrogenism was still associated with an increased risk of preterm delivery (OR=3.67, 95%CI: 1.67-8.07). Compared with women with normoandrogenic PCOS, women with hyperandrogenic PCOS had similar risks of pregnancy loss, gestational diabetes mellitus, pre-eclampsia, placenta previa, and postpartum hemorrhage (all P>0.05). Birth weight as well as the risks of being small for gestational age and large for gestational age were also comparable between the two groups (all P>0.05). Conclusion: In women with PCOS and singleton pregnancy, those with preconceptional hyperandrogenism have a higher risk of preterm delivery than those without hyperandrogenism.

[Therapeutic effects and related mechanisms of erythropoietin sustained-release gelatin hydrogel microspheres on a murine model of hindlimb ischemia].

OBJECTIVE: To investigate the therapeutic effects of erythropoietin sustained-release gelatin hydrogel microspheres (EPO-GHM) on a murine model of hindlimb ischemia and related mechanisms. METHODS: Fifty two ten weeks old male C57BL/6J mice were assigned to 5 groups: sham-operated group (the right femoral artery suture was passed through the right femoral artery but not tied, n=8); saline group (right femoral artery ligation and intramuscular injection of saline at a dose of 4 ml/kg into the right hind limb, n=12); EPO group(right femoral artery ligation and intramuscular injection of EPO at a dose of 5 000 IU/kg into the right hind limb, n=12), empty GHM group (right femoral artery ligation and intramuscular injection of empty GHM at a dose of 4 ml/kg into the right hind limb, n=8); EPO-GHM group(right femoral artery ligation and intramuscular injection of EPO-GHM at a dose of 5 000 IU/kg into the right hind limb, n=12). The blood flow ratio of ischemic limb (right)/nonischemic limb (left) was measured using a laser Doppler perfusion imager. After 8 weeks, immunohistochemical analysis were used to evaluate the vessel density (vessel density of CD31 positive), arteriole density(vessel density of α-smooth muscle actin(α-SMA) positive) and muscle area(HHF35 positive area). The proliferating index of vessels was evaluated by double immunofluorescent labeling to evaluate effect of EPO-GHM on angiogenesis of ischemia limb. Western blot was used to evaluate the protein expression of EPO receptor, protein kinase B(AKT), p-AKT, endothelial nitric oxide synthase(eNOS), p-eNOS and matrix metalloproteinase 2(MMP-2). RESULTS: (1) Eight weeks later, the blood flow ratio of ischemic limb/nonischemic limb was significantly higher in the EPO-GHM group compared with other groups(0.810±0.080, 0.563±0.051, 0.570±0.056 and 0.561±0.052 respectively, all P<0.05). (2) CD31 antibody positive and α-SAM antibody positive densities were higher in the EPO-GHM group compared with other groups(P<0.01 or 0.05). (3)HHF35 positive area in saline group, EPO group, empty GHM group and EPO-GHM group were smaller than that of sham-operated group(all P<0.05). HHF35 positive area in saline group, EPO group, empty GHM group and EPO-GHM group were similar(all P>0.05). (4)The proliferating index of vessels was higher in the EPO-GHM group compared with other groups(P<0.01 or 0.05). (5) Compared with other groups, the protein levels of EPO receptor, AKT, p-AKT, p-eNOS and MMP-2 were significantly higher in EPO-GHM group(P<0.01 or 0.05) and level of eNOS was similar among five groups(P>0.05). CONCLUSION: RESULTS from present study suggest EPO-GHM could improve blood perfusion of ischemia limb in mice through increasing capillary and arteriolar densities and these beneficial effects are possibly mediated by EPOR up-regulation and AKT/p-eNOS/MMP-2 signaling pathway activation.

The chromosomal effect of birchen dust as determined by the micronucleus test.

In a wood processing factory, the measured air concentration of birchen dust was 1.26 +/- 0.41 mg/m3, and the micronucleus frequency of peripheral blood lymphocytes in 83 workers exposed to wood dust was 1.13 +/- 2.83/1000, which was significantly higher (P < 0.01) than that of control group (0.51 +/- 1.41/1000). The number of exposed workers with positive micronucleus test was 9.6%, which was higher than that of control group (4.5%), but the difference was not significant (P > 0.05). The micronucleus test in mice treated with water extracts of unsteamed and unbaked birchen dust showed that the micronucleus frequencies in all treated groups were significantly higher than that of control group (P < 0.01) and there was also a dose response correlation (r = 0.96, P < 0.0005). The results of steamed and baked birchen dust extracts were significantly lower than those of the unsteamed and unbaked ones at the same doses (P < 0.001). This suggests that when the birchen dust is steamed at the temperature of 100 degrees C for 24 h or baked at the temperature of 80 degrees C, its inducing effect in micronucleus test could be lowered.

[Effect of recombinant human growth factors: recombinant human interleukin-6, recombinant human granulocyte-macrophage colony-stimulating-factor and recombinant human erythropoietin on normal human hematopoietic progenitor cells].

The effect of recombinant human growth factors: rhIL-6, rhGM-CSF and rhEPO on normal human hematopoietic progenitor cells was studied by using liquid and semisolid culture systems. The results showed that the expanding folds of progenitor cells after culturing with the three growth factors were 4.3 +/- 0.6, 9.4 +/- 0.9 and 13.7 +/- 1.0 respectively, being markedly higher than those of control (2.4 +/- 0.7, P < 0.01. In the presence of IL-6 alone, no CFU-E colony was observed and only CFU-GM colonies were formed in the semisolid culture. When IL-6 was added with EPO, the number of CFU-E colonies was significantly higher than that of EPO alone (P < 0.01). In the presence of IL-6 plus GM-CSF or IL-6 plus GM-CSF and EPO, CFU-Mix colonies were observed. Moreover, the total number of colonies was significantly higher than that of IL-6 or GM-CSF alone (P < 0.01). It is suggested that IL-6 is an important hematopoietic regulator. IL-6 may act on hematopoietic progenitor cells to enhance their proliferation. The target cells of IL-6 are the same as those of GM-CSF. IL-6 has synergistic action with EPO and GM-CSF, to enhance erythropoiesis with EPO and proliferation of multipotential progenitor cells with rhGM-CSF and EPO. However, the mechanism of the synergism between IL-6 and other growth factors is still unknown.