Objective: To explore the indication and surgery scope for laparoscopic extraperitoneal lymphadenectomy in locally advanced cervical cancer. Methods: Laparoscopic extraperitoneal lymphadenectomy was initially performed on patients with locally advanced cervical cancer. The results of preoperative computed tomography (CT) images and serum level of squamous cell carcinoma antigen (SCC-Ag) were analyzed, and the diagnostic efficiencies of the minimum axial diameter (MAD) of lymph node on CT≥0.5 cm, ≥1.0 cm, serum level of SCC-Ag alone or combined to predict the extraperitoneal lymph node metastases were compared. The high-risk factors of common iliac lymph node (CILN) and para-aortic lymph node (PALN) metastases were also analyzed. Results: The lymph node metastasis rate of 81 patients who received the laparoscopic extraperitoneal lymphadenectomy was 59.3% (48/81). The CILN and/or PALN metastasis rate was 24.7%(20/81), and among them, the MAD of CILN and/or PALN ≥0.5 cm on CT images were in only 7 patients. The threshold of SCC-Ag for evaluating lymph node metastasis was 4.8 ng/ml. The accuracy, specificity and Youden index of SCC-Ag≥4.8+ MAD≥1.0 cm group for predicting lymph node metastasis were 78.3%, 100% and 0.6, respectively, and were significantly higher than 57.9%, 12.1% and 0.1 of MAD≥0.5 cm group, 71.1%, 75.8% and 0.4 of MAD≥1.0 cm group, 65.0%, 57.7% and 0.3 of SCC-Ag≥4.8 ng/ml group and 68.3%, 65.4% and 0.4 of SCC-Ag≥4.8 ng/ml+ MAD≥0.5 cm group (P<0.05). All of the 21 patients in SCC-Ag≥4.8 ng/ml+ MAD≥1.0 cm group were detected to occur lymph node metastases, and the metastasis rate of CILN and/or PALN was 38.1%. While only 4 cases of 17 patients in SCC-Ag<4.8 ng/ml+ MAD<1 cm group were confirmed to occur CILN metastases. The difference of lymph node metastasis rate between these two groups was statistically significant (P<0.001). The pathological type, the number of PLN with MAD≥1.0 cm, at least one of the PLN MAD≥1.0 cm and/or MAD of CILN and/or PALN was 0.5~1.0 cm were associated with the CILN and/or PALN metastases (all P<0.05). Conclusions: Those patients with MAD≥1.0 cm+ SCC-Ag≥4.8 ng/ml and with high-risk factors of CILN and/or PALN metastases should undergo laparoscopic extraperitoneal lymphadenectomy to provide explicit guidance for the subsequent therapy. However, the incidence of lymph node metastasis of patients with SCC-Ag<4.8 ng/ml combined with MAD<1.0 cm is low, therefore these patients can accept concurrent chemoradiotherapy directly.目的： 探讨局部晚期宫颈癌腹腔镜下腹膜后淋巴结切除的适应证和手术范围。 方法： 选择初治的局部晚期宫颈癌患者行腹腔镜下腹膜后淋巴结切除术，分析患者术前CT影像资料和血清鳞状细胞癌抗原(SCC－Ag)水平，比较CT淋巴结最短径(MAD)≥0.5 cm、MAD≥1.0 cm和SCC－Ag水平预测腹膜后淋巴结转移的价值，分析髂总淋巴结(CILN)和(或)腹主动脉旁淋巴结(PALN)转移的高危因素。 结果： 81例患者行腹腔镜下腹膜后淋巴结切除术，淋巴结转移率为59.3%(48/81)；CILN和(或)PALN转移率为24.7%(20/81)，其中仅7例CT示CILN和(或)PALN短径≥0.5 cm。SCC－Ag水平判断淋巴结转移的临界值为4.8 ng/ml，SCC－Ag≥4.8 ng/ml＋CT淋巴结MAD≥1.0 cm判断淋巴结转移的准确率、特异度和约登指数分别为78.3%、100%和0.6，与CT淋巴结MAD≥0.5 cm组(分别为57.9%、12.1%和0.1)、MAD≥1.0 cm组(分别为71.1%、75.8%和0.4)、SCC－Ag≥4.8 ng/ml组(分别为65.0%、57.7%和0.3)和SCC－Ag≥4.8 ng/ml＋CT淋巴结MAD≥0.5 cm组(分别为68.3%、65.4%和0.4)比较，差异均有统计学意义(均P<0.05)。SCC－Ag≥4.8 ng/ml＋CT淋巴结MAD≥1.0 cm组21例，术后均出现淋巴结转移，淋巴结转移率为100%(21/21)，其中38.1%(8/21)出现CILN和(或)PALN转移；而SCC－Ag<4.8 ng/ml＋CT淋巴结MAD<1.0 cm组17例，术后仅4例出现髂总以下盆腔淋巴结(PLN)转移，淋巴结转移率为24.0%(4/17)，两组患者的淋巴结转移率差异有统计学意义(P<0.001)。病理类型、CT示MAD≥1.0 cm PLN淋巴结数目、CT示1个PLN MAD≥1.0 cm±MAD 0.5～1.0 cm CILN和(或)PALN均与CILN和(或)PALN转移有关(均P<0.05)。 结论： CT淋巴结MAD≥1.0 cm且SCC－Ag≥4.8 ng/ml以及存在CILN和(或)PALN转移高危因素者，可行髂总以下肿大淋巴结切除取样以及CILN和PALN切除，以明确淋巴结转移状况，为后续治疗提供准确指导。CT淋巴结MAD<1.0 cm且SCC－Ag<4.8 ng/ml者，淋巴结转移率低，可直接行同步放化疗。.
We demonstrate that gastrin-releasing peptide (GRP) can inhibit the proliferation of human immortal nontumorigenic (184-B5) mammary epithelial cells ectopically expressing the human GRP receptor. Growth of Balb 3T3 cells ectopically expressing relatively high levels of the GRP receptor was also inhibited by GRP; however, growth of transfectants expressing lower levels of the receptor was not inhibited. Compared with Balb 3T3 cells, mammary epithelial cells could be rendered sensitive to growth inhibition by GRP by the expression of fewer GRP receptors. GRP also stimulated DNA synthesis in quiescent, serum-starved Balb 3T3 transfectants. In clones that were sensitive to growth inhibition by GRP by virtue of their expression of relatively high levels of the GRP receptor, the dose-response curve of GRP-stimulated DNA synthesis was bell shaped. This is consistent with our conclusion that the growth-inhibiting activity of GRP required the activation of a relatively large pool of receptors in Balb 3T3 cells. Significantly, prostaglandin H synthase inhibitors, which block the production of prostaglandins from arachidonic acid, reduced GRP-inhibitory effects on DNA synthesis. We also compared a number of GRP-stimulated signaling pathways in Balb 3T3 clones that were sensitive or insensitive to growth inhibition by GRP, including cAMP formation, phospholipase C activation, calcium mobilization, and arachidonic acid formation. Taken together, these results demonstrate a novel GRP receptor-coupled signal pathway promoting growth inhibition in which prostaglandin H synthase plays a significant role.
To analyze the clinicopathologic feature of Stage I A I squamous carcinoma of the cervix (SCC) and to explore the outcome of different surgical methods.Clinicopathological data of 346 cases with Stage I Al SCC diagnosed between November 2nd, 1995 and December 31st, 2011 were reviewed and analyzed.As major diagnostic method, 44.5% (154/346) patients accepted cold knife conization (CKC), while 58.1% (201/346) patient took total hysterectomy (TH) as their final surgical methods. The trend in treatment methods from 1995 to 2011 revealed that increasing cases were treated with CKC, modified radical hysterectomy (MRH) obviously reduced, while the proportion treated by TH remained unchanged. Due to a small number of cases receiving vaginal trachelectomy (VT) and radical trachelectomy (RT), the authors did not find any obvious changes.The overall recurrence rate was 1.2% (4/346). The overall survival rates for CKC, VT, TH, MRH, and RT were 100%, 100%, 98.2%, 100%, and 100%, and the difference was not statistically significant (p = 0.819). The incidence rate of LVSI was 4.9% (17/346), the overall survival rates for patients with LVSI and without LVSI were 99.3% and 93.3%, respectively, and there was statistical difference between them (p = 0.003). Univariate analysis showed that only LVSI was an important predictor for survival (p = 0.030).the treatments for Stage I Al SCC are becoming more conservative, and individualized therapy and more frequent surveillance should be administrated to those patients with LVSI.
Background: Uterine leiomyoma (UL) is the most common benign smooth muscle tumor of the uterus in reproductive women. Prior studies indicated that methyl-CpG-binding domain proteins (MBDs) may be involved in the pathogenesis of UL. Materials and Methods: In this study, UL tissues and paired adjacent myometrium were collected from a total of 51 patients. The expression of MBD mRNAs and their cognate proteins were analyzed via quantitative polymerase chain reaction assays and western blotting, respectively. The relationships between the MBD expression levels and the patients' clinicopathologic variables were assessed using Student's t test, nonparametric tests, or Pearson χ2 methods. Results: Our results show that both the mRNA and protein levels of MBD2 were significantly decreased in ULs compared to the adjacent myometrium. In addition, MBD6 protein expression was also decreased significantly in UL samples when compared to the adjacent myometrium. There was, however, no significant difference on the mRNA expression of MBD6 between these two groups. Neither the mRNA nor the protein levels of the other MBD members (MBD1, MBD3, MBD4, MBD5, and MeCP2) showed any significant differences between ULs and the adjacent myometria. The decreased expression of the MBD6 protein was correlated with the tumor size of ULs. Conclusions: These results suggest that the dysregulated expression of MBD2 and MBD6 in ULs may play a role in their development; however, a larger sample size together with cellular functional assays should be carried out to further elucidate the precise role of MBD6 in ULs.
Objective To evaluate the feasibility and safety of vaginal enlarged amputation of cervix to treat patients with cervical cancer of stage Ⅰ a1 and cervical intraepithelial neoplasia grade Ⅲ(CIN Ⅲ)who were unfit for conization surgery.Methods From July 2002 to May 2007,patients with cervical cancer at stage Ⅰ a1,diagnosed by pathology after loop electrosurgical excision procedure(LEEP),large area CIN Ⅲ(the area of lesion≥3/4 on colposcopy),CIN Ⅲ coexisted with vaginal intraepithelial neoplasia (VAIN)in the superior segment of vagina,CIN Ⅱ-Ⅲ recurrence or with residual lesion,positive margin after conization of cervix,who wanted to preserve fertility and(or)corpus uteri were selected to receive vaginal enlarged amputation of cervix.Results Forty-eight eases including 5 with cervical cancer in stage Ⅰ a1,38 with large area CIN Ⅲ(9 with gland involvement),2 with residual lesion and 2 with positive margin after LEEP,1 recurrence after cold knife conization,received the procedure successfully.The median age was 34 years(range 27-40),median operation time was 60 minutes(range 30-100),median blood loss was 40 ml(range 5-300),and median hospital stay was 10 days(range 7-17).After follow-up 1-39 months,no patient had postoperative complications and recurrence,and all patients resumed normal menstrual cycle and sexual life.Condusion Vaginal enlarged amputation of cervix appears to be a safe and feasible procedure for patients with cervical cancer at stage Ⅰ a1 and CIN Ⅲ who are unfit for conization surgery.
Key words:
Cervix neoplasms; Carcinoma,squamous cell; Cervical intraepithelial neoplasia; Cervix uteri; Gynoeologie surgical procedures
The aim of this study was to evaluate the therapeutic value and treatment-related complications of adjuvant chemotherapy after concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC).The medical records of LACC patients who underwent CCRT were reviewed retrospectively.A total of 1,138 patients with LACC who had been treated at our hospital between January 2013 and December 2017 were included in the study and classified into two groups: the CCRT group, comprising 726 patients who had received only CCRT, and the CCRT + adjuvant chemotherapy (ACT) group, comprising 412 patients who had received three cycles of adjuvant chemotherapy after CCRT. 39 patients in the CCRT group and 50 patients in the CCRT + ACT group had undergone lymphadenectomy, which revealed pathology-positive lymph nodes in 22 patients and 35 patients, respectively. Progression-free survival (PFS), overall survival (OS), and adverse events were compared.The median follow-up time was 61 months (range: 2-96 months). No significant differences in PFS and OS were found between the two groups (p > 0.05), but more grade 3-4 acute hematologic toxicities were observed in the CCRT + ACT group than in the CCRT group (24.8% vs. 31.8%, p = 0.01). A subgroup analysis of patients with pathology-positive lymph nodes showed that the 5-year PFS and OS rates were 76.5% and 74.9%, respectively, for the CCRT + ACT group and 45.0% and 49.2%, respectively, for the CCRT group; the differences were statistically significant (p = 0.015 and 0.042, respectively).First, the sample size of the subgroup of patients with pathology-positive lymph nodes was too small for a confirmative conclusion. The heterogeneous population and the selection bias resulting from the retrospective design were the other flaws of our study.The application of adjuvant chemotherapy after CCRT may be worth investigating further for women with LACC and pathology-positive lymph nodes, but this approach is associated with an increase in acute hematology toxicities.
Chemotherapy resistance is a leading cause of treatment failure in cases of cervical adenocarcinoma (ADC), and no effective treatment approach has yet been found. We previously identified the differentially expressed kynureninase (KYNU) mRNA in cervical adenocarcinoma cells (HeLa) and cervical adenocarcinoma cisplatin resistance cells (HeLa/DDP) using gene chips. However, the role and potential mechanism of KYNU in the cisplatin resistance of cervical adenocarcinoma remain unclear.We verified the expression of KYNU in the cells and tissues of ADC patients and analyzed its correlation with patient prognosis. A stable HeLa/DDP cell line with KYNU mRNA knockdown was constructed. We then used a CCK8 assay to detect cell survival, a transwell assay to evaluate cell migration and proliferation and flow cytometry to measure apoptosis. The effect of KYNU silence on cisplatin sensitivity was evaluated in an orthotopic model of metastatic ADC. Immunohistochemistry was performed to determine the changes in relevant drug resistance-associated protein expression, aiming to explore the underlying mechanism of KYNU-mediated drug resistance.KYNU is overexpressed in HeLa/DDP cells and tissues and is associated with the poor prognoses of patients with ADC. After KYNU mRNA knockdown, the invasion, migration, and proliferation of HeLa/DDP cells in the cisplatin environment significantly reduced, while the apoptosis rate of HeLa/DDP cells significantly increased. Meanwhile, KYNU knockdown improved the DDP sensitivity of ADC in vivo. Furthermore, silencing KYNU decreased the expressions of CD34 and the drug-resistance related proteins P-gp, MRP1, and GST-π and increased the level of the proapoptotic regulatory protein Bax.KYNU deficiency enhanced DDP sensitivity by suppressing cell proliferation, migration, and invasion and promoting apoptosis in DDP-resistant ADC cells in vitro. Furthermore, KYNU knockdown improved the drug sensitivity of ADC in vivo. The results showed that KYNU is involved in the chemotherapy resistance of cervical adenocarcinoma.
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