Analysis of treatment modalities and prognosis on microinvasive cervical cancer: a 10-year cohort study in China

Qiuhong Qian,Jiaxin Yang,Dongyan Cao,Yan You,Jie Chen,Keng Shen 대한부인종양학회 2014 Journal of Gynecologic Oncology Vol.25 No.4

Objective: To explore appropriate treatment modality of microinvasive cervical cancer (MIC) and to analyze prognosis and risk factors of recurrence. Methods: A cohort of 324 Chinese patients with MIC diagnosed and treated at Peking Union Medical College Hospital was retrospectively reviewed. Demographic features, treatment modalities, pathologic parameters, risk factors of residual disease, survival and risk factors of recurrence were analyzed. Results: Of all patients, 280 cases were staged IA1 and 44 cases staged IA2 MIC. Twenty-five cases (7.7%) were found to have lympho-vascular space involvement (LVSI), but no parametrial involvement or ovarian metastasis was detected. Only one staged IA2 patient with LVSI was found to have lymph node metastasis. 32.4% patients (82/253) had residual diseases after conization. No significant difference of LVSI, lymph node metastasis and residual disease after coniztion was found between stage IA1 and IA2 MIC patients. Multivariate logistic analysis showed positive margin was the only independent risk factor of residual disease after conization (odds ratio [OR], 4.18; p<0.001). Recurrence occurred in five cases, but no mortality was found. Progression-free survival for stage IA1 patients treated by conization or hysterectomy was similar (92.3% and 98.8%, p=0.07). Cox regression analysis revealed LVSI as an independent risk factor for recurrence in stage IA1 patients (OR, 12.14; p=0.01). Conclusion: For stage IA1 patients with negative resection margin and no LVSI, conization can be an ideal treatment modality. For stage IA2 patients, more conservative surgery such as simple hysterectomy may be considered. LVSI is an independent risk factor for recurrence in patients with stage IA1 cervical cancer.

Tailored therapy and long-term surveillance of malignant germ cell tumors in the female genital system: 10-year experience

Qianying Zhao,Jiaxin Yang,Dongyan Cao,Jiangna Han,Kaifeng Xu,Yongjian Liu,Keng Shen 대한부인종양학회 2016 Journal of Gynecologic Oncology Vol.27 No.3

Objective: To explore the appropriate treatment of malignant germ cell tumor (MGCT) in thefemale genital system, and to analyze the factors influencing both therapeutic response andsurvival outcome. Methods: A cohort of 230-Chinese women diagnosed with MGCT of the genital systemwas retrospectively reviewed and prospectively followed. The demographic and pathologicalfeatures, extent of disease and surgery, treatment efficiency, recurrence and survival wereanalyzed. Results: MGCTs from different genital origins shared a similar therapeutic strategy andresponse, except that all eight vaginal cases were infantile yolk sac tumors. The patients’ curerate following the initial treatment, 5-year overall survival and disease-free survival (DFS)were 85.02%, 95.00%, and 86.00%, respectively. Although more extensive excision couldenhance the remission rate; it did not improve the patients’ survival. Instead, the level of themedical institution, extent of surgery and disease were independent prognostic factors forrelapse (p<0.05). Approximately 20% of patients had recurrent or refractory disease, morethan half of whom were in remission following secondary cytoreductive surgery with salvagechemotherapy. Conclusion: Fertility-sparing surgery with or without standardized PEB/PVB (cisplatin,etoposide/vincristine, and bleomycin) chemotherapy is applicable for female MGCTsof different origins. Comprehensive staging is not required; nor is excessive debulkingsuggested. Appropriate cytoreduction by surgery and antineoplastic medicine at anexperienced medical institution can bring about an excellent prognosis for these patients.

Completion hysterectomy after chemoradiotherapy for locally advanced adeno-type cervical carcinoma: updated survival outcomes and experience in post radiation surgery

Jie Yang,Jiaxin Yang,Dongyan Cao,Keng Shen,Jiabin Ma,Fuquan Zhang 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.2

Objective: To compare patient survival outcomes between completion hysterectomy and conventional surveillance in locally advanced adenocarcinoma of the cervix after concurrent chemoradiotherapy (CCRT). Methods: Patients with adenocarcinoma of the cervix after CCRT were identified in a tertiary academic center database from 2004 to 2018. Patients received completion hysterectomy or surveillance after CCRT. We compared the progression-free survival (PFS) and overall survival (OS) between the patients with or without adjuvant hysterectomy. Surgery features, operative complications, and pathologic characteristics were documented. Patient outcomes were also analyzed according to clinicopathologic factors. Results: A total of 78 patients were assigned to completion surgery and 97 to surveillance after CCRT. The PFS was better in the surgery group compared to the CCRT only group, at 3 years the PFS rates were 68.1% and 45.2%, respectively (hazard ratio [HR]=0.46; 95% confidence interval [CI]=0.282–0.749; p=0.002). Adjuvant surgery was also associated with a higher rate of OS (HR=0.361; 95% CI=0.189–0.689; p=0.002), at 3 years, 87.9% and 67%, respectively. Tumor stage, size, lymph-vascular space invasion (LVSI), lymphadenopathy were associated with PFS but not with OS. Hysterectomy specimens revealed 64.1% (50/78) of the patients had pathologic residual tumor. Patients age less than 60, tumor size over 4 cm, stage IIB and persistent residual disease after CCRT were most likely to benefit from hysterectomy. Hysterectomy was associated with a lower rate of locoregional recurrence but did not reach statistical significance (5.13% vs. 13.5%, p=0.067). Conclusion: Completion hysterectomy after CCRT was associated with better survival outcome compared with the current standard of care.

Germline and somatic mutations in homologous recombination genes among Chinese ovarian cancer patients detected using next­generation sequencing

Qianying Zhao,Jiaxin Yang,Lei Li,Dongyan Cao,Meiyun Ke,Keng Shen,BGI Group 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.4

Objective: To define genetic profiling of homologous recombination (HR) deficiency inChinese ovarian cancer patients. Methods: We have applied next-generation sequencing to detect deleterious mutationsthrough all exons in 31 core HR genes. Paired whole blood and frozen tumor samples from50 Chinese women diagnosed with epithelial ovarian carcinomas were tested to identify bothgermline and somatic variants. Results: Deleterious germline HR-mutations were identified in 36% of the ovarian cancerpatients. Another 5 patients had only somatic mutations. BRCA2 was most frequentlymutated. Three out of the 5 somatic mutations were in RAD genes and a wider distributionof other HR genes was involved in non-serous carcinomas. BRCA1/2-mutation carriers hadfavorable platinum sensitivity (relative risk, 1.57, p<0.05), resulting in a 100% remissionprobability and survival rate. In contrast, mutations in other HR genes predicted poorprognosis. However, multivariate analysis demonstrated that platinum sensitivity andoptimal cytoreduction were the independent impact factors influencing survival (hazardsratio, 0.053) and relapse (hazards ratio, 0.247), respectively. Conclusion: Our results suggest that a more comprehensive profiling of HR defect thanmerely BRCA1/2 could help elucidate tumor heterogeneity and lead to better stratification ofovarian cancer patients for individualized clinical management.

Production and Optimization of a Kiwi Pectin Methylesterase Inhibitor in Pichia pastoris GS115

Qian Liu,Wentao Xu,Shiwen Han,Dongyan Cao,Xiaoyun He,Kunlun Huang,Xiaohong Mei 한국식품과학회 2014 Food Science and Biotechnology Vol.23 No.6

Gene sequence coding of a kiwi pectin methylesteraseinhibitor was optimized, synthesized, and expressedin Pichia pastoris GS115 based on P. pastoris preferredcodon usage. The expression level of the recombinantprotein (kwPMEI) increased by 89.74% after codonoptimization. Expression conditions of recombinant strainswere optimized. The highest production of kwPMEI wasachieved using 0.8% sorbitol (added every 24 h), 0.05%oleic acid (added at the beginning of induction), and 0.5%methanol (added every 12 h). kwPMEI was purified usingNi2+ chelating affinity chromatography and 17 mg of theprotein was harvested from 60 mL of a culture supernatant. Activity analysis showed that kwPMEI efficiently inhibitedthe activity of different plant PMEs. High expression levelsand purification of kwPMEI will promote applications infruit and vegetable juices.

Extrafascial hysterectomy after concurrent chemoradiotherapy in locally advanced cervical adenocarcinoma

Jie Yang,Keng Shen,Jinhui Wang,Jiaxin Yang,Dongyan Cao 대한부인종양학회 2016 Journal of Gynecologic Oncology Vol.27 No.4

Objective: To evaluate whether adjuvant simple hysterectomy after concurrent chemoradiotherapy (CCRT) improves progression-free survival (PFS) compared with current standard care in locally advanced cervical adenocarcinoma (LACAC). Methods: We reviewed a cohort of 55 patients with LACAC (International Federation of Gynecology and Obstetrics [FIGO] stage IB2, IIA2, IIB, III without distant metastasis) diagnosed and treated with radical CCRT at Peking Union Medical College Hospital between January 2004 and October 2014. We compared 34 patients who underwent adjuvant extrafascial hysterectomy with 21 patients with standard care after CCRT. The primary outcome was PFS. Overall survivals (OS) between the two groups were also compared. Surgery feasibility, operative complications, and pathologic features after radiation therapy were also analyzed. Results: PFS was significantly improved in surgery group (log-rank p=0.0097; hazard ratio [HR], 0.3431; 95% CI, 0.152 to 0.772), as were OS (log-rank p=0.0419; HR, 0.3667; 95% CI, 0.139 to 0.964). Analysis of stage IIB demonstrates a similar result. There were no severe complications related to postradiation surgery in this series. The mean blood loss was less in laparoscopic group than those in the open group (87 mL vs. 208 mL, p=0.036, Mann-Whitney U-test). Approximately 47% patients (16/34) had pathologic residue tumor on hysterectomy specimens. About 94% patients (32/34) got complete remission after adjuvant surgery. Conclusion: Adjuvant hysterectomy after CCRT improves survival outcome for patients with LACAC compared with current standard care. Extrafascial hysterectomy is sufficient in tumor reduction and laparoscopic procedure may be more promising with lower blood loss and expedite recovery.