Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial.

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma.

Endometrial cancer (EC) is a major cause of death among gynecologic malignancies. To improve early detection of EC in patients, we carried out a large plasma-derived exosomal microRNA (miRNA) studies for diagnostic biomarker discovery in EC. Small RNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 56 plasma samples from healthy subjects and EC patients. These miRNA candidates were further validated in 202 independent plasma samples by droplet digital PCR (ddPCR), 32 pairs of endometrial tumors and adjacent normal tissues by quantitative real-time PCR (qRT-PCR), and matched plasma samples of 12 patients before and after surgery by ddPCR. miR-15a-5p, miR-106b-5p, and miR107 were significantly upregulated in exomes isolated from plasma samples of EC patients compared with healthy subjects. Particularly, miR-15a-5p alone yielded an AUC value of 0.813 to distinguish EC patients with stage I from healthy subjects. The integration of miR-15a-5p and serum tumor markers (CEA and CA125) achieved a higher AUC value of 0.899. There was also a close connection between miR-15a-5p and clinical manifestations in EC patients. Its exosomal expression was not only associated with the depth of muscular infiltration and aggressiveness of EC, but also correlated with levels of reproductive hormones such as TTE and DHEAS. Collectively, plasma-derived exosomal miR-15a-5p is a promising and effective diagnostic biomarker for the early detection of endometrial cancer.

BRCA mutations in the manifestation and treatment of ovarian cancer.

BRCA genes are important for the integrity and stability of genetic material and play key roles in repairing DNA breaks via high fidelity homologous recombination. BRCA mutations are known to predispose carriers to gynecological malignancies, accounting for a majority of hereditary OC cases. Known to be lethal, OC is difficult to detect and control. Testing for BRCA mutations is a key step in the risk assessment, prognosis, treatment and prevention of OC and current clinical guidelines recommend BRCA mutation testing for all OCs of epithelial origin. Studies have established that ovarian tumors harboring BRCA mutations have distinct molecular and histo-pathological features that can be exploited for effective, targeted treatment. Deficiencies in DNA repair pathways that arise as a result of BRCA mutations make them hypersensitive to DNA-damaging treatments such as platinum chemotherapy and PARP inhibitors. Different combinations of treatment regimens which have the potential to greatly improve prognosis and disease outcomes are currently being evaluated. However, the issue of developing resistance to these treatments remains unresolved. This review emphasizes unique features of BRCA mutated OC and outlines the lay of the land in terms of diagnosis and treatment, while aiming to unravel the challenges that are part of its management.

[Gestational trophoblastic diseases in cesarean scar: an analysis of 20 cases].

OBJECTIVE: To analyze the clinical features, diagnosis and treatment of gestational trophoblastic diseases in cesarean scar. METHODS: Clinical data of three cases of gestational trophoblastic diseases in cesarean scar diagnosed in Women's Hospital, Zhejiang University School of Medicine during December 2011 and December 2016 were collected. And literature search was performed in Wanfang data, VIP, CNKI, PubMed, ISI Web of Knowledge and EMbase database. RESULTS: A total of 20 cases of gestational trophoblastic diseases were included in the analysis. Clinical features were mainly abnormal vaginal bleeding after menopause, artificial abortion or medical abortion, which might be accompanied by abdominal pain. Serum ß-human chorionic gonadotropin (ß-hCG) levels were increased in 19 patients. The sonographic features were increase of uterine volume, honeycomb-like abnormal intrauterine echo (or described as multiple cystic dark area, multiple anechoic area and multiple liquid dark area) or heterogeneity echo conglomeration, and no clear bound with muscular layer in some cases. There were abundant blood flow signals inside or around the lesions. The ultrasonography indicated that the lesions were located in the anterior side of the uterine isthmus with the involvement of cesarean section scar. In 12 cases with lesions in cesarean scar shown by preliminary diagnosis, 9 underwent uterine artery embolization (UAE) for pretreatment; the blood loss greater than 1500 mL was observed in only one case without UAE; no patient received hysterectomy. In 8 patients whose lesions were not shown in cesarean scar, only one case received UAE pretreatment, and hysterectomy was performed in 3 cases due to blood loss greater than 1500 mL. Two cases were lost in follow-up and no death was reported in remaining 18 cases. The serum ß-hCG levels returned to normal or satisfactory level during the follow-up in 17 cases with increased ß-hCG levels before treatment and no recurrence was observed. CONCLUSIONS: The misdiagnosis rate and missed diagnosis rate of gestational trophoblastic diseases in cesarean section scar are high. The identification of cesarean section scar involvement and UAE may reduce the bleeding and avoid hysterectomy.

Identification of Cathepsin K in the Peritoneal Metastasis of Ovarian Carcinoma Using In-silico, Gene Expression Analysis.

Ovarian carcinomas (OC) are often found in the advanced stage with wide peritoneal dissemination. Differentially-expressed genes (DEGs) between primary ovarian carcinoma (POC) and peritoneal metastatic ovarian carcinomas (PMOC) may have diagnostic and therapeutic values. In this study, we identified 246 DEGs by in-silico analysis using microarrays for 153 POCs and 57 PMOCs. Pathway analysis shows that many of these genes are associated with lipid metabolism. Microfluidic, card-based, quantitative PCR validated 19 DEGs in PMOCs versus POCs (p<0.05). Immunohistochemistry confirmed overexpression of MMP13, CTSK, FGF1 and GREM1 in PMOCs (p<0.05). ELISA detection indicated that serum CTSK levels were significantly increased in OCs versus controls (p<0.001). CTSK levels discriminated between OCs and healthy controls (ROC 0.739; range 0.685-0.793). Combining CA125 and HE4 with CTSK levels produced an improved specificity in the predictive of OCs (sensitivity 88.3%, specificity 92.0%, Youden's index 80.3%). Our study suggests that CTSK levels may be helpful in the diagnosis of primary, ovarian carcinoma.

Iatrogenic parasitic leiomyoma and leiomyomatosis peritonealis disseminata following uterine morcellation.

AIM: To assess the impact of morcellation on the spread of uterine leiomyoma. METHODS: Cases of parasitic leiomyoma involving prior laparoscopy were collected between 2012 and 2015 in a tertiary women's hospital in China. Their clinicopathological features and the associated reports were reviewed. RESULTS: All six patients with parasitic leiomyoma had laparoscopic myomectomy or hysterectomy with power morcellation 39-132 months previously. Patient 1 had widely disseminated tumors in the peritoneum and pelvis, in keeping with leiomyomatosis peritonealis disseminata (LPD). She received debulking of peritoneal tumors and lived with disease for 22 months. The implanting sites of the other parasitic tumors (patients 2-6) included the mesentery (n = 2), intestine (n = 1), pelvic parietal (n = 1), bladder (n = 1), and musculus rectus abdominis (n = 1). The diameter varied from 1 cm to 6 cm. The patients underwent abdominal subtotal hysterectomy, cervicectomy or tumor debulking and the postoperative course was unremarkable for a period of 2-32 months. Pathologically, these disseminated or parasitic leiomyomas did not show any evidence of malignancy. There were no morphological or immunohistochemical differences between the original tumor and the following seeding tumors. On literature review, 11 iatrogenic LPD have been reported after laparoscopic surgery for uterine leiomyoma. These cases may provide an alternative pathogenic mechanism for a distinct variant of LPD. CONCLUSIONS: Laparoscopic hysterectomy with tumor morcellation may increase the chance of tumor implantation and dissemination. Both clinicians and pathologists should be alert to this rare complication.

Analyses of functional and oncologic outcomes following supracricoid partial laryngectomy.

To review the functional and oncologic outcomes of patients who received supracricoid partial laryngectomy (SCPL) with cricohyoidoepiglottopexy (CHEP) or cricohyoidopexy (CHP) in our institution. A total of 208 patients who received SCPL with CHEP or CHP from our institution from 1995 to 2007 were involved. Among them, 190 cases were patients with squamous cell carcinoma of the larynx (T1-T4, N0-N2), 14 cases were patients with recurrent larynx cancer and 4 cases were patients with laryngeal stenosis. Forty-four patients also received unilateral neck dissection, and 41 patients received a bilateral neck dissection. All patients were assessed at functional outcome and complications of their treatment. Also, the oncologic outcomes, such as disease-specific survival, total survival, and local recurrence, were measured for patients with tumor. Decannulation was achieved in nearly all patients, with the average time to decannulation being 20 ± 11.52 days in CHEP patients and 28 ± 8.92 days in CHP patients (P < 0.05). The average nasogastric tubes were removed, days postoperation, was 18 ± 7.39 days in CHEP patients and 25 ± 13.87 days in CHP patients (P < 0.05). The 5-year local recurrence rate was 5.77%, the 5-year disease-specific survival was 82.7%, and the 5-year overall survival was 84.1%. The patients with CHEP had a better recovery than the patients with CHP. SCPL was a well-tolerated procedure with generally good functional outcomes for patients with advanced laryngeal cancer, also for some patients with laryngeal stenosis.

Clinical outcomes and prognostic factors of patients with epithelial ovarian cancer subjected to first-line treatment: a retrospective study of 251 cases.

A total of 251 patients with epithelial ovarian cancer (EOC) treated between 2002 and 2008 was retrospectively analyzed to investigate the long-term outcomes and prognostic factors of these patients, particularly those who underwent primary debulking surgery followed by platinum-based chemotherapy. Clinicopathological parameters, including progression-free survival (PFS) and overall survival (OS), were also analyzed. The median follow-up period from the end of initial treatment to June 2010 was 58 months. The three-year PFS rate was 61.7% for International Federation of Gynecology and Obstetrics (FIGO) I-II, 19.9% for FIGO III-IV, and 33.9% for all stages. By comparison, the five-year PFS rate was 44.6% for FIGO I-II, 17.7% for FIGO III-IV, and 28.3% for all stages. The three-year OS rate was 67.9% for FIGO I-II, 41.7% for FIGO III-IV, and 50.2% for all stages. The five-year OS rate was 52.7% for FIGO I-II, 30.8% for FIGO III-IV, and 39.2% for all stages. Univariate analysis revealed that advanced FIGO stage, serum CA125, and suboptimal debulking were significant factors affecting PFS and OS. In multivariate analysis, PFS was significantly influenced by FIGO stage and suboptimal debulking. However, OS was significantly influenced by advanced FIGO stage only. Our study confirms the efficacy of surgery followed by platinum-based chemotherapy for EOC. FIGO stage is considered as one of the most reliable predictors of the prognosis of patients with EOC.

Retrospective analysis on coexisting ovarian cancer in 976 patients with clinical stage I endometrial carcinoma.

AIM: To evaluate the safety of ovarian preservation at the time of operation in clinical stage I endometrial carcinoma. MATERIAL AND METHODS: The data of patients with and without coexisting ovarian cancers were retrospectively collected and clinic-pathologic parameters were analyzed. RESULTS: In total, 20 (2.05%) were histologically diagnosed as coexisting ovarian cancer, including 17 (1.74%) ovarian metastases and three (0.31%) synchronous ovarian primary cancers in 976 patients. Fifty percent (10 of 20) were microscopic ovarian involvements. Ovarian involvement was significantly associated with histological type, depth of myometrial invasion, cervical invasion, uterine serosa extension, fallopian tube involvement, retroperitoneal lymph node metastasis, positive peritoneal cytology and CA125 level by univariate analysis (all P<0.05); while cervical invasion, uterine serosa extension, and fallopian tube involvement were independent high-risk factors by multivariate analysis (both P<0.05). CONCLUSION: The incidence of coexisting ovarian cancer in clinical stage I endometrial carcinoma is low, but the decision for ovary preservation at the time of operation still needs to be made with caution because of occult ovarian metastasis, especially for patients with high-risk factors.

[The relationship between different types of lymph node metastasis and contralateral neck metastasis and their impact on prognosis].

OBJECTIVE: To study the relationship between different types of lymph node metastasis and contralateral neck metastasis and their impacts on prognosis. METHOD: Two hundred and forty-eight patients with supraglottic carcinomas and complete follow-up were analyzed retrospectively. Transparent lymph node detection and continuous sectioning methods were applied on postoperative neck specimens. RESULT: Cervical lymph node metastases were found in 115 patients and the lymph node metastatic rate was 46.4%. There were three types of lymph node metastases, 39 cases with single type, 34 with multiple type, 42 with fusion type. Contralateral metastatic rates were 5.1%, 44.1% and 61.9% in single, multiple and fusion type respectively. Contralateral metastasis was also related with tumor extension across midline and clinical N stages. The 3- and 5-year survival rates were 79.5% and 74.4% in single type, 61.8% and 41.2% in multiple type, 61.9% and 35.7% in fusion type. CONCLUSION: Bilateral neck dissections should be undertaken in multiple and fusion types of lymph node metastasis. The lymph node metastatic type should be an important criteria to judge prognosis.

[Clinic and pathological analysis the larynx leukoplakia in 74 cases].

OBJECTIVE: To study the clinic and pathological features of leukoplakia of the larynx, and reduce canceration rate. METHOD: Seventy-four postoperative patients of leukoplakia of the larynx were followed up for four years by telephone or clinic service. RESULT: None of eighteen cases of pure leukoplakia was recurrence. Fifty-six cases were leukoplakia with epithelial dysplasia histologically. Seven out of fifty-six postoperative cases occurred hoarseness; three out of fifty-six postoperative cases recurred, and accepted twice or more operations successively; three out of fifty-six postoperative cases occurred canceration. CONCLUSION: Operation is the main means for the treatment of leukoplakia of the larynx, and the effect is comparatively well. The patients with histological epithelial dysplasia should be pay great attention because of their higher canceration rate, and enlarged operation ranges appropriately with the patient consent could effectually prevent recurrence or canceration during the early lesions. Close observation is important for these patients.

[Accuracy of preoperative tumor grading and intraoperative gross examination of myometrial invasion in clinical stage I endometriod adenocarcinoma].

OBJECTIVE: To evaluate accuracy of preoperative tumor grade and intraoperative gross examination of myometrial invasion in patients with clinical stage I endometriod adenocarcinoma for lymphadenectomy. METHODS: Clinic-pathological data were retrospectively collected from 687 patients with clinical stage I endometriod adenocarcinoma who underwent operation in Women's Hospital, Zhejiang University School of Medicine from January 1999 to December 2008. According to postoperative histology diagnosis, accuracy of preoperative tumor grade by curettage and depth of myometrial invasion by intraoperative gross examination was evaluated, and clinic-pathological factors associated with accuracy were analyzed. RESULTS: Sensitivity, specificity, accuracy, false negative rate, false positive rate, and positive and negative predictive value for the prediction of needing for intraoperative lymphadenectomy in patients with clinical stage I endometriod adenocarcinoma were 70.4%, 80.2%, 77.6%, 12.0%, 43.0%, 57.0% and 88.0%, respectively. Analysis of muti-factors shown that patient age, tumor size, lymph node metastasis and extrauterine spread lesions were independent factors affected the accuracy of prediction (P < 0.05). CONCLUSION: Prediction of needing for lymphadenectomy by preoperative tumor grade and intraoperative gross examination of myometrial invasion is reliable in clinical stage I endometriod adenocarcinoma patients, while there is a highly false negative rate in prediction of not needing for lymphadenectomy, while other prognostic factors such as patient age, tumor size, lymph node metastasis and extrauterine spread lesion should be together considered.

Accuracy of tumor grade by preoperative curettage and associated clinicopathologic factors in clinical stage I endometriod adenocarcinoma.

BACKGROUND: Preoperative tumor grading becomes one of the most important predictors for lymphadenectomy at primary surgery for clinical stage I endometriod adenocarcinoma. However, there is an inconsistency of tumor grade between preoperative curettage and final hysterectomy specimens, and its associated factors are poorly understood. This study aimed to evaluate the accuracy of tumor grade by preoperative curettage so as to achieve a better stratified management for clinical stage I endometriod adenocarcinoma. METHODS: Clinical data of totally 687 patients with clinical stage I endometriod adenocarcinoma who underwent preoperative curettage and primary surgery were retrospectively collected. Compared with final hysterectomy specimens, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of tumor grade by preoperative curettage were calculated and their associations with clinicopathologic parameters, including age, status of menopause, position of uterus, location and size of lesion, histological grade, depth of myometrial invasion, cervical invasion, extrauterine spread, peritoneal cytology, metastasis to retroperitoneal lymph node, serum CA125 level, and hormone receptor status, were analyzed. RESULTS: In final hysterectomy specimens, 139 of 259 grade 1 patients by curettage were upgraded to grade 1 or 2; 31 of 296 grade 2 were upgraded to grade 3, with a significantly discrepant rate of 40.9% (281/687) and an upgraded rate of 24.7% (170/687). The specificity and negative predictive value for grade 3 were 90.7% and 89.9%, while the sensitivity and positive predictive value for grade 1 were 67.1% and 40.9%, respectively. CONCLUSIONS: Preoperative tumor grade by curettage does not accurately predict final histological results, especially in those classified as grade 1. Complete surgical staging seems to be necessary for clinical stage I endometriod adenocarcinoma.

[Expression of gene BRMS1 and CD44v6 protein in supraglottic laryngeal carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression of breast cancer metastasis suppressor 1 (BRMS1) and CD44v6 protein in supraglottic cancer and to evaluate its clinical significance. METHOD: The expression of BRMS1 protein and CD44v6 protein were examined by using immunohistochemical method in 70 cases of paraffin-embedded supraglottic cancer tissues and their surrounding laryngeal normal mucosa tissues (LNT). RESULT: The expression of BRMS1 protein in LNT of supraglottic cancer was positive, and the positive rate was 85.7% (60/70); in tumor tissue was negative or lower expression, and the positive rate was 35.7% (25/70). The expression of CD44v6 protein in tumor tissue of supraglottic cancer was positive, the positive rate was 82.9% (58/70), in LNT was negative. There was a significant difference in BRMS1 and CD44v6 protein expression between the supraglottic cancer tissue and LNT (P<0.01). The expression of BRMS1 and CD44v6 protein had correlation with clinical stage and pathologic differentiation and cervical lymph node metastasis of supraglottic cancer (P<0.01). No correlation was found between the two proteins expression and sex and age (P>0.05). The expression of BRMS1 protein was related to the expression of CD44v6 protein (r = -0.9042, P<0.01). Calculated by Kaplan-Meier method, there is no survival difference at 3-year between the group with positive BRMS1 protein expression and the group with negative BRMS1 protein expression in tumor tissues (P>0.05), there is a significant survival difference at 3-year between the group with positive CD44v6 protein expression and the group with negative CD44v6 protein expression in tumor tissues (P<0.05). CONCLUSION: The expression of BRMS1 protein in supraglottic cancer is significantly decreased and the expression of CD44v6 protein in supraglottic cancer is significantly increased. The expression of BRMS1 protein and CD44v6 protein has a close relationship with pathologic differentiation and clinical stage and cervical lymph node metastasis of supraglottic cancer. Combined detection of the expression of them in supraglottic cancer may provide a significant parameter to judge the cervical lymph node metastasis of supraglottic cancer.

[Long-term follow-up study of 559 cases with laryngeal carcinoma].

OBJECTIVE: To study the long-term follow-up result of partial laryngectomy and reservation of laryngeal function. METHODS: Five hundred and fifty-nine patients who underwent partial laryngectomy from 1996 to 2002 were summarized (male 435 cases, female 124 cases). Among them, 200 cases were supraglottic carcinomas (classified accordingly by UICC standard of years 2002 into: 15 cases of I, 81 cases of II, 72 cases of III, and 32 cases of IV), 354 cases were glottic carcinomas (141 cases of I, 124 cases of II, 88 cases of III, and 1 cases of IV), 5 cases were transglottic carcinomas (2 cases of II and 3 cases of III). In common 7 kinds of operations were performed: 66 cases underwent cordectomy, 119 vertical laryngectomy, 62 horizontal supraglottic laryngectomy, 113 horizontovertical (3/4) laryngectomy, 88 subtotal laryngectomy with cricoglossoepiglottic anastomosis, 26 near total laryngectomy with cricoglossal anastomosis (with reservation of unilateral arytenoid cartilage), 85 laser laryngectomy. Two hundred and sixty-one cases underwent concurrent neck dissection (174 unilateral, 87 bilateral). Safety margin of less than or equal to 5 mm was suspected of having residual lymph node metastasis, the postoperative radiation therapy to treatment. RESULTS: All cases restored their phonation and overcame aspiration with removing nasal feeding from 7 to 24 days after operations. Four hundred and sixty-six cases were decannulated from 9 days to 3 months after operations. Decannulation rate was 98.3%. Through periodic review of out-patient clinics or telephone follow-up, family members follow-up a variety of ways, three, five or ten years follow-up rate: 99.6% (557/559), 98.2% (549/559), 95.8% (183/191), dollars lost to death. The three years survival rates were 89.6% (501/559). Among them, the survival rates for supraglottic carcinoma patients of stage I and II was 90.6%, stage III and IV 81.7%, for glottic carcinoma patient of stage I and II was 95.2%, stage III and IV 82.4%. The five years survival rates were 75.0% (419/559). Among them, the survival rates for supraglottic carcinoma patients of stage I and II was 75.0%, stage III and IV 62.5%, for glottic carcinoma patient of stage I and II was 81.8%, stage III and IV 70.6%. The ten year survival rates were 71.2% (136/191). Among them, the survival rates for supraglottic carcinoma patients of stage I and II was 69.7%, stage III and IV 65.2%, for glottic carcinoma patient of stage I and II was 77.6%, stage III and IV 72.1%. CONCLUSIONS: Partial laryngectomy is a kind of radical operation with reservation of laryngeal function. Qualities of life and curative effect, were greatly improved.

Activation of signal transducers and activators of transcription 3 and overexpression of its target gene CyclinD1 in laryngeal carcinomas.

OBJECTIVES/HYPOTHESIS: Constitutive activation of signal transducers and activators of transcription (STAT) 3 has been observed in many solid tumors including head and neck squamous cell carcinoma. Expression and activation of STAT3 in laryngeal carcinoma have not been fully understood. The study aims to investigate the expression and activation of STAT3 in laryngeal carcinoma, the relationship between activated STAT3 and its downstream target gene CyclinD1 and the related clinicopathological factors of activated STAT3. STUDY DESIGN: Prospective. METHODS: Sixty-four samples of laryngeal squamous cell carcinoma and 12 samples of control mucosa obtained from total laryngectomy cases were analyzed using Western blot analysis and reverse transcriptase-polymerase chain reaction. Statistical analysis was performed using SPSS. RESULTS: The overexpression of both STAT3 and CyclinD1 mRNA was observed in all samples of laryngeal squamous cell carcinoma. The mRNA levels of STAT3 and CyclinD1 in carcinoma tissue were 2.1- and 2.3-fold higher than those in control mucosa, respectively; the differences were statistically significant (P < .01). The overexpression of STAT3, p-STAT3, and CyclinD1 protein was also observed in all tumor samples. The protein levels of STAT3, p-STAT3, and CyclinD1 in carcinoma tissue were 1.6-, 4.5-, and 2.0-fold higher than those in control mucosa respectively; the differences were statistically significant (P < .01). There was a positive correlation between p-STAT3 protein and CyclinD1 mRNA (Pearson correlation coefficient = 0.827, P < .01). There were significant correlations between the overexpression of p-STAT3 protein and clinical T stage (P < .01), and tumor size (P < .05). The p-STAT3 protein level of patients in T1, T2 was higher than that of patients in T3, T4. The p-STAT3 protein level of patients with tumor size within 20 mm was higher than that of patients with tumor size more than 20 mm. CONCLUSIONS: High expression and activation of STAT3 exist in laryngeal carcinomas. Activated STAT3 may take effect on promoting transcription of its downstream target gene CyclinD1. The role of activation of STAT3 in laryngeal carcinogenesis needs further research.

[Expression and clinical significance of breast cancer metastasis suppressor 1 mRNA in supraglottic laryngeal carcinoma].

OBJECTIVE: To investigate the expression of breast cancer metastasis suppressor 1 (BRMS1) mRNA in supraglottic cancer and to evaluate its clinical significance. METHOD: The expression of BRMS1 mRNA was examined by using RT-PCR method which take beta-actin mRNA as reference template in 66 cases of supraglottic cancer tissues and their adjacent normal mucosa tissues (ANT). RESULT: The expression of BRMS1 mRNA in the tissues of supraglottic cancer is lower significantly than that in the tissues of ANT ( P<0.05). There is correlation between BRMS1 mRNA expression and the clinical stage, differentiation and cervical lymph node metastasis in the laryngeal supraglottic cancers (P<0.05). There is no correlation between BRMS1 mRNA expression and sex and age. CONCLUSION: Expression of BRMS1 mRNA in supraglottic cancer is lower than that in adjacent normal mucosa. The decrease of BRMS1 mRNA expression may be related to clinical stage and low differentiation and lymph node metastasis of supraglottic laryngeal cancer.

Analysis of curative effects on laryngeal carcinoma patients in the northeast region of China.

CONCLUSIONS: In the past 20 years, the level of laryngeal carcinoma treatment in our country has been significantly improved. Early diagnosis is the key for increasing the ratio of larynx preservation surgeries and improving survival rates. The main causes of death within 5 years are local recurrence and metastasis. OBJECTIVE: To describe the main treatment methods for laryngeal carcinoma in China in the 1980s and 1990s and their prospective effects and investigate the prognostic factors. PATIENTS AND METHODS: A retrospective investigation was performed on the 1115 laryngeal carcinoma patients receiving treatment in the department of ENT of the First Affiliated Hospital of China Medical University during 1983-1996 and the survival rates and causes of death were analyzed statistically. RESULTS: There were 780 patients surviving for more than 5 years, 260 dead patients, and 75 patients lost to follow-up. According to the cumulative survival rate curve, the 5-year survival rate was 77% (94% for stage I, 89% for stage II, 82% for stage III, and 66% for stage IV). Glottic cancer has the highest 5-year survival rate, followed by supraglottic cancer, subglottic cancer, and transglottic cancer. The 5-year survival rate of patients receiving partial laryngectomy was 85%, while the 5-year survival rate of those receiving total laryngectomy was 68%. The leading causes of death within 5 years were local recurrence and metastasis (70%), and the causes of death were unknown in 14% of cases.

[Expression and prognostic significance of cyclooxygenase-2 in supraglottic laryngeal squamous cell carcinomas].

OBJECTIVE: To study the expression and prognostic significance of cyclooxygenase-2 (Cox-2) in supraglottic laryngeal squamous cell carcinomas (SGLSCC) and identify the relationship between Cox-2 and angiogenesis and the roles of Cox-2 in SGLSCC as a biological marker. METHOD: Eighty-eight primary SGLSCC patients received surgical treatment were studied by immunohistochemical staining, and reverse transcription-polymerase chain reaction (RT-PCR) technique. RESULT: The percentage of Cox-2-positive cells was 94.3% (83/88) in SGLSCC whereas there was no immunostaining in the all cells of normal mucosa of paracarcinoma. Cox-2 expression was higher in well-differentiated tumors compared with poorly-differentiated SGLSCC. The relative concentration of Cox-2 mRNA was 141.871 +/- 20.5435 in SGLSCC and 17.031 +/- 2.2597 in normal paracarcinoma mucosa (P < 0.01). It was significantly higher in SGLSCC than in normal paracarcinoma mucosa. In SGLSCC, only pathological grading and the percentage of Cox-2-positive cells had significant correlation (P < 0.01). And not only the percentage of Cox-2-positive cells but also Cox-2 intensity had significant correlation with microvessel density (MVD) (P < 0.01). Kaplan-Meier survival analysis showed there had significant relationship between Cox-2 intensity and cumulative survival rate of SGLSCC patients (P < 0.05). But the percentage of Cox-2-positive cells was different (P > 0.05). Cox's regression analysis indicated that Cox-2 intensity were significantly independent prognostic factors (P < 0.01). CONCLUSION: Cox-2 expression maybe relate to the carcinogenesis and progress in tumors especially in well-differentiated ones; The changes of Cox-2 expression are synchronous with MVD. Cox-2 intensity is a significantly independent prognostic factor. So Cox-2 may be an effective target of prevention, therapy and prognostic evaluation for laryngeal carcinoma and other head and neck squamous cell carcinomas (HNSCC).