Ting Wan

SPAG5 upregulation predicts poor prognosis in cervical cancer patients and alters sensitivity to taxol treatment via the mTOR signaling pathway.

Previously, we found that sperm-associated antigen 5 (SPAG5) was upregulated in pelvic lymph node metastasis–positive cervical cancer. The aim of this study is to examine the role of SPAG5 in the proliferation and tumorigenicity of cervical cancer and its clinical significance in tumor progression. In our study, SPAG5 expression in cervical cancer patients was detected using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry; cervical cancer cell function with downregulated SPAG5 in vitro was explored using tetrazolium assay, flow cytometry, and colony formation and Transwell assays. SPAG5 was upregulated in tumor tissue compared with paired adjacent noncancerous tissues; SPAG5 upregulation in tumor tissues indicated poor disease-free survival, which was also an independent prognostic indicator for cervical cancer patients. In vitro study demonstrated that SPAG5 downregulation inhibited cell proliferation and growth significantly by G2/M arrest and induction of apoptosis, and hindered cell migration and invasion. Under SPAG5 downregulation, the sensitivity of cervical cancer cells differed according to taxol dose, which correlated with mammalian target of rapamycin (mTOR) signaling pathway activity. In general, SPAG5 upregulation relates to poor prognosis in cervical cancer patients, and SPAG5 is a regulator of mTOR activity during taxol treatment in cervical cancer.

Clinical outcome of 31 patients with primary malignant melanoma of the vagina

Objective To investigate the clinical characteristics of and prognostic factors for primary malignant melanoma of the vagina. Methods Clinical data from 31 patients treated for primary malignant melanoma of the vagina at the Sun Yat-sen University Cancer Center between March 1970 and June 2005 were retrospectively analyzed. Results The median age was 58 years (range, 18 to 73 years), and the main symptoms reported were vaginal bleeding and vaginal discharge. Most tumors were of the nodular type and classified as stage I according to International Federation of Gynecology and Obstetrics staging criteria. Surgery was performed on 22 patients, chemotherapy was administered to 7 patients, and immunotherapy was administered to 19 patients. Recurrent tumors developed in 11 patients (35.5%) during a median follow-up period of 20.2 months (range, 1 month to 18 years). The 5-year overall survival rate was 32.3%. Univariate analysis revealed that macroscopic tumor growth and the treatment method significantly affected survival outcome (p=0.039 and p<0.001, respectively), whereas the radicality of surgery did not (p=0.296). Multivariate analysis revealed that macroscopic tumor growth (hazard ratio [HR], 4.1; 95% confidence interval [CI], 1.4 to 12.1; p=0.010) and treatment method (HR, 0.3; 95% CI, 0.1 to 0.9; p=0.025) were independent prognostic factors for overall survival. Conclusion Patients with primary vaginal melanoma have a poor prognosis. Macroscopic tumor growth and treatment method are prognostic factors for primary malignant melanoma of the vagina.

Metastasis to deep obturator and para-aortic lymph nodes in 649 patients with cervical carcinoma.

OBJECTIVE The extent of retroperitoneal lymph node dissection for early stage cervical cancer remains debatable. Our study aimed to investigate the incidence of metastases in deep obturator lymph nodes (DOLNs) and para-aortic lymph nodes (PALNs) and its association with clinicopathological factors in cervical carcinoma. METHOD Six hundred and forty-nine patients with stage IB to IIB cervical cancer underwent radical hysterectomy, pelvic lymphadenectomy and/or para-aortic lymphadenectomy. The incidence and distribution of metastases in retroperitoneal lymph nodes and the associated factors were analyzed. RESULTS Metastases in pelvic lymph nodes (PLNs) were found in 175 patients. Of the 175 cases with positive PLNs, 15 had DOLN metastases. Only two cases without PLN metastases had positive DOLNs. There was no significant correlation between DOLN metastasis and tumor histology, differentiation or capillary lymphatic space involvement. PALN metastasis occurred in 19 of 137 patients with cervical lesions larger than 2 cm in diameter. Eighteen of the 19 patients also had PLN involvement. Logistic regression analysis showed that PLN metastasis and larger tumors were independent risk factors for metastasis to PALNs. CONCLUSION DOLN metastasis is not common and may be secondary to metastasis to other PLNs. Routine removal of DOLNs might be unnecessary when PLNs are negative. Para-aortic sampling or lymphadenectomy should be considered when the PLNs are positive or/and the cervical lesion is larger than 2 cm.

Prognostic and Safety Roles in Laparoscopic Versus Abdominal Radical Hysterectomy in Cervical Cancer: A Meta-analysis

Abstract Objective: Studies comparing the prognostic results between laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) in cervical cancer reported contradictory results. We aimed to evaluate the prognostic and safety roles of LRH by pooling studies in a meta-analysis. Materials and Methods: Original articles were searched in PubMed, EMBASE, and the Cochrane Library. The survival results (5-year disease-free survival [DFS], 5-year overall survival [OS], and recurrence rate [RR]), safety parameters (intra-, peri-, and postoperative complication rates and postoperative bowel or bladder recovery days), efficiency parameters (pelvic/para-aortic lymph nodes removed), and other parameters (operative time, estimated blood loss, and hospital of stay) between the two approaches were reviewed. Results: For the 2922 cases identified, DFS, OS, and RR did not differ in balanced prognostic factors, including lymph node metastasis, Stage IIB or above, non–squamous cancer histology, grade G3, lymphovascular space invasion, tumor size ≥4 cm, and positive parametrial and vaginal margin rates. Meanwhile, LRH was associated with higher complication rates and a shorter time to the recovery of bowel or bladder function than for ARH. The number of removed pelvic or para-aortic lymph nodes did not significantly differ. Other parameters showed LRH was associated with a longer operative time, less blood loss, and a shorter length of hospital stay. The survival and prognostic results did not differ in balanced prognostic factors. Conclusions: LRH is safe and has lower operative complication rates than ARH.

Neoadjuvant docetaxel combined with cisplatin and followed by radical surgery for the treatment of locally advanced (stage IB2 – IIB) cervical cancer: preliminary results of a single-institution experience

Objectives: We aimed to determine the efficacy and toxicity of treating locally advanced cervical cancer (LACC) with a neoadjuvant chemotherapy (NAC) regimen combining docetaxel and cisplatin followed by radical surgery. Methods: We retrospectively reviewed the clinical records of patients with stage IB2 – IIB (tumor diameter ≥ 4 cm) disease admitted between January 2007 and July 2009 who, before radical hysterectomy and pelvic lymph node dissection, received two to three courses of an NAC regimen comprising docetaxel (75 mg/m2) and cisplatin (70 – 75 mg/m2). Results: Fifty-two patients with LACC received 109 cycles of NAC. The objective response rate was 86.5% (26.9% CR and 17.3% pathological CR). Stage IB2 disease had a more favorable response to NAC (95.7%, p = 0.019). Deep stromal invasion and lymph-vascular space metastasis rates were significantly lower in NAC responders (p = 0.033) than in nonresponders (p = 0.012). Most side effects of NAC were mild or moderate. Log-rank test showed the 2-year overall survival and progression-free survival rates were 100 and 90.3% for NAC responders, compared with only 57.1% (p = 0.000) and 68.6% for nonresponders (p = 0.012), respectively. Conclusion: Neoadjuvant docetaxel combined with cisplatin yielded a high response rate with well tolerable toxicity for LACC and could decrease pathological risk factors in NAC responders.

Large animal model for retroperitoneal lymphatic and lung metastasis

Retroperitoneal lymph node and lung metastasis are important prognostic factors for gynecologic cancer. The present study aimed to develop a new animal model for retroperitoneal lymph node and lung metastasis. VX2 squamous cell carcinoma tumor tissues were injected into the left gastrocnemius muscle of 38 healthy female New Zealand white rabbits. Animals were randomized into three groups according to day of sacrifice: 1, day 19; 2, day 22; and 3, day 25. Implanted primary tumor (IPTu), left and right retroperitoneal lymph node volumes and lung wet weights were measured on the day of sacrifice. The IPTu and left and right retroperitoneal lymph node volumes increased in a time-dependent manner. In addition, the proportion of animals with metastasis to the left peritoneal lymph nodes and the number of nodes involved increased over time. For days 19, 22 and 25, the proportion of animals with nodal metastasis was 58.3, 84.6 and 100%, respectively, and the number of affected nodes (range) was 3 (2–3), 3 (3–5) and 4 (4–5), respectively. No metastasis was detected in the right peritoneal lymph nodes. Metastasis to the lungs also increased with time, but was not statistically significant at days 19, 22 and 25 with metastasis present in 33.3, 38.5 and 76.9% of animals, respectively. Rates of metastases to the left retroperitoneal lymph nodes and lungs were found to positively correlate with the volumes (r=0.416 and 0.449, respectively). The current study assessed the characterization of a rabbit VX2 carcinoma model. This animal model is likely to be useful for evaluating retroperitoneal lymph node and lung metastasis.

The bidirectional regulation between MYL5 and HIF-1α promotes cervical carcinoma metastasis

Myosin light chains (MLC) serve important regulatory functions in a wide range of cellular and physiological processes. Recent research found that MLC are also chromatin-associated nuclear proteins which regulate gene transcription. In this study, the MLC member myosin regulatory light chain 5 (MYL5) expression was upregulated in late stage cervical cancer patients, positively correlated with pelvic lymph node metastasis, and identified as a poor survival indicator. MYL5 overexpression promoted metastasis in cervical cancer in vitro and in vivo models, whereas MYL5 silencing had the converse effect. We demonstrated a bidirectional regulation between MYL5 and hypoxia inducible factor-1α (HIF-1α). HIF-1α activates MYL5 via binding to the hypoxia response element (HRE) in the promoter of MYL5, and MYL5 could sustain HIF-1α expression by tethering to recognition sequence AGCTCC in the HIF-1α promoter region. Clinical data confirmed a positive correlation between MYL5 and HIF-1α. In summary, our data show that MYL5 may act as a prognosis predictive factor in cervical carcinoma, and strategies that inhibit the interaction of MYL5 and HIF-1α may benefit the cervical carcinoma patients with metastasis.

Individualized Treatment of Patients With Early-Stage Epithelial Ovarian Cancer After Incomplete Initial Surgery.

Objectives Incomplete initial surgery complicates subsequent management of early-stage epithelial ovarian carcinoma (ESEOC). This study aimed to determine the most appropriate strategies for individualized treatment of these patients. Methods Medical records of ESEOC patients treated at our hospital between 2000 and 2011 were reviewed, and 246 patients initially treated by incomplete surgery were included. A scoring system was established to assess the quality of initial surgery (QOIS). Results Of 246 patients, 130 underwent restaging surgery and 116 received chemotherapy only. Follow-up duration ranged from 4 to 148 months (median, 72 months). The 5-year overall survival (OS) rates were 87.5% and 74.7% in the restaging and chemotherapy groups, respectively. Survival analysis showed significantly better recurrence-free survival (RFS) and OS in the restaging group (P = 0.043 and P = 0.029, respectively). Multivariate analysis showed that histologic grade was an independent predictor for RFS and OS in the restaging group (P = 0.035 and P = 0.038, respectively), and histologic grade (P = 0.005 and P = 0.015, respectively) and QOIS (P = 0.044 and P = 0.024, respectively) were independent predictors for RFS and OS in the chemotherapy group. Subgroup analysis showed that restaging surgery produced better RFS and OS than chemotherapy in patients with low QOIS and unfavorable histology (5-year RFS, 58.5% vs 33.4%, P = 0.007; 5-year OS, 82.2% vs 54.4%, P = 0.011), whereas the outcomes between the treatment options were comparable in patients with high QOIS or favorable histology. Conclusions Our results support individualized treatment of ESEOC patients initially treated by incomplete surgery. Restaging surgery is recommended only for patients with low QOIS and unfavorable histology.