Concurrent definitive chemoradiation incorporating intensity-modulated radiotherapy followed by adjuvant chemotherapy in high risk locally advanced cervical squamous cancer: a phase II study.

BACKGROUND: Although the prognosis of locally advanced cervical cancer has improved dramatically, survival for those with stage IIIB-IVA disease or lymph nodes metastasis remains poor. It is believed that the incorporation of intensity-modulated radiotherapy into the treatment of cervical cancer might yield an improved loco-regional control, whereas more cycles of more potent chemotherapy after the completion of concurrent chemotherapy was associated with a diminished distant metastasis. We therefore initiated a non-randomized prospective phaseII study to evaluate the feasibility of incorporating both these two treatment modality into the treatment of high risk locally advanced cervical cancer. OBJECTIVES: To determine whether the incorporation of intensity-modulated radiotherapy and the addition of adjuvant paclitaxel plus cisplatin regimen into the treatment policy for patients with high risk locally advanced cervical cancer might improve their oncologic outcomes. STUDY DESIGN: Patients were enrolled if they had biopsy proven stage IIIA-IVA squamous cervical cancer or stage IIB disease with metastatic regional nodes. Intensity-modulated radiotherapy was delivered with dynamic multi-leaf collimators using 6MV photon beams. Prescription for PTV ranged from 45.0 ~ 50.0 Gy at 1.8 Gy ~ 2.0 Gy/fraction in 25 fractions. Enlarged nodes were contoured separately and PTV-nodes were boosted simultaneously to a total dose of 50.0-65 Gy at 2.0- 2.6 Gy/fraction in 25 fractions. A total dose of 28 ~ 35 Gy high-dose- rate brachytherapy was prescribed to point A in 4 ~ 5 weekly fractions using an iridium- 192 source. Concurrent weekly intravenous cisplatin at 30 mg/m2 was initiated on the first day of radiotherapy for over 1-h during external-beam radiotherapy. Adjuvant chemotherapy was scheduled within 4 weeks after the completion of concurrent chemo-radiotherapy and repeated 3 weeks later. Paclitaxel 150 mg/m2 was given as a 3-h infusion on day1, followed by cisplatin 35 mg/m2 with 1-h infusion on day1-2 (70 mg/m2 in total). RESULTS: Fifty patients achieved complete response 4 weeks after the completion of the treatment protocol, whereas 2 patients had persistent disease. After a median follow-up period of 66 months, loco-regional (including 2 persistent disease), distant, and synchronous treatment failure occurred in 4,5, and 1, respectively. The 5-year disease-free survival, loco-regional recurrence-free survival, distant-metastasis recurrence-free survival was 80.5%, 90.3%, and 88.0%, respectively. Four of the patients died of the disease, and the 5-year overall survival was 92.1%. Most of the toxicities reported during concurrent chemo-radiotherapy were mild and transient. The occurrence of hematological toxicities elevated mildly during adjuvant chemotherapy, as 32% (16/50) and 4% (2/50) patients experienced grade 3-4 leukopenia and thrombocytopenia, respectively. Grade 3-4 late toxicities were reported in 3 patients. CONCLUSIONS: The incorporation of intensity-modulated radiotherapy and adjuvant paclitaxel plus cisplatin chemotherapy were highly effective and well-tolerated in the treatment of high-risk locally advanced cervical cancer. The former yields an improved loco-regional control, whereas distant metastases could be effectively eradicated with mild toxicities when adjuvant regimen was prescribed.

Laparoscopic pectopexy: the learning curve and comparison with laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: In addition to laparoscopic sacrocolpopexy (LS), laparoscopic pectopexy (LP) is a novel surgical method for correcting apical prolapse. The descended cervix or vaginal vault is suspended with a synthetic mesh by fixing the bilateral mesh ends to the pectineal ligaments. This study was aimed at developing a learning curve for LP and to compare it with results with LS. METHODS: We started laparoscopic/robotic pectopexy in our department in August 2019. This retrospective study included the initial 18 consecutive women with apical prolapse receiving LP and another group undergoing LS (21 cases) performed by the same surgeon. The medical and video records were reviewed. RESULTS: The age was older in the LP group than in the LS group (65.2 vs 53.1 years). The operation time of LP group was significantly shorter than that of the LS group (182.9 ± 27.2 vs 256.2 ± 45.5 min, p < 0.001). The turning point of the LP learning curve was observed at the 12th case. No major complications such as bladder, ureteral, bowel injury or uncontrolled bleeding occurred in either group. Postoperative low back pain and defecation symptoms occurred exclusively in the LS group. During the follow-up period (mean 7.2 months in LP, 16.2 months in LS), none of the cases had recurrent apical prolapse. CONCLUSIONS: Laparoscopic pectopexy is a feasible surgical method for apical prolapse, with a shorter operation time and less postoperative discomfort than LS. LP may overcome the steep learning curve of LS because the surgical field of LP is limited to the anterior pelvis and avoids encountering the critical organs.

Identification and validation of a novel glycolysis-related gene signature for predicting the prognosis in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is the most lethal gynaecological tumor. Changes in glycolysis have been proven to play an important role in OC progression. We aimed to identify a novel glycolysis-related gene signature to better predict the prognosis of patients with OC. METHODS: mRNA and clinical data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Genotype Tissue Expression (GTEx) database. The "limma" R package was used to identify glycolysis-related differentially expressed genes (DEGs). Then, a multivariate Cox proportional regression model and survival analysis were used to develop a glycolysis-related gene signature. Furthermore, the TCGA training set was divided into two internal test sets for validation, while the ICGC dataset was used as an external test set. A nomogram was constructed in the training set, and the relative proportions of 22 types of tumor-infiltrating immune cells were evaluated using the "CIBERSORT" R package. The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined by single-sample gene set enrichment analysis (ssGSEA) with the "GSVA" R package. Finally, the expression and function of the unreported signature genes ISG20 and SEH1L were explored using immunohistochemistry, western blotting, qRT-PCR, proliferation, migration, invasion and xenograft tumor assays. RESULTS: A five-gene signature comprising ANGPTL4, PYGB, ISG20, SEH1L and IRS2 was constructed. This signature could predict prognosis independent of clinical factors. A nomogram incorporating the signature and three clinical features was constructed, and the calibration plot suggested that the nomogram could accurately predict the survival rate. According to ssGSEA, the signature was associated with KEGG pathways related to axon guidance, mTOR signalling, tight junctions, etc. The proportions of tumor-infiltrating immune cells differed significantly between the high-risk group and the low-risk group. The expression levels of ISG20 and SEH1L were lower in tumor tissues than in normal tissues. Overexpression of ISG20 or SEH1L suppressed the proliferation, migration and invasion of Caov3 cells in vitro and the growth of xenograft tumors in vivo. CONCLUSION: Five glycolysis-related genes were identified and incorporated into a novel risk signature that can effectively assess the prognosis and guide the treatment of OC patients.

Nasogastric tube decompression is unnecessary in patients undergoing laparoscopic nephroureterectomy for localized upper tract urothelial carcinoma.

BACKGROUND/PURPOSE: This study investigates the safety and feasibility to perform laparoscopic nephroureterectomy (LNU) for upper tract urothelial carcinoma (UTUC) without routine nasogastric tube (NGT) decompression. METHODS: The hospital-based samples comprised of 100 consecutive UTUC patients receiving elective LNU performed by two experienced surgeons. The nationwide data was based on LHID2005 composed of one million beneficiaries randomly selected from the Taiwan National Health Insurance Research Database to identify patients with the diagnoses of UTUCs receiving LNUs. We then compared baseline characteristics, peri-operative data, convalescence parameters and complications between two groups stratified by use of NGT tube. RESULTS: The hospital-based samples composed of 50 subjects with NGT and 50 without. There were no significant differences in baseline characteristics between two groups. Peri-operative and convalescence parameters were similar when comparing no NGT versus NGT: blood loss of 206 vs. 165 mL; operative time of 180.5 vs.181.1 min; days to intake was 2.1 vs.1.7 days; and hospital stay of 7.8 vs. 7.5 days (all p > 0.05). The nationwide study samples comprised 140 subjects, of which 72 were with NGT and 68 were with no NGT. The baseline data, complications and length of hospital stay were similar between two groups. CONCLUSION: Surgery-naïve patients with localized UTUC received LNU without peri-operative NGT is safe and feasible.

Comparison Study of Laparoscopic Sentinel Lymph Node Mapping in Endometrial Carcinoma Using Carbon Nanoparticles and Lymphatic Pathway Verification.

STUDY OBJECTIVE: To evaluate the detection rate and accuracy of sentinel lymph node (SLN) mapping using cervical and fundal injections of carbon nanoparticles (CNPs) in laparoscopic surgery of endometrioid endometrial cancer (EC) and to identify uterine lymphatic drainage pathways validated by mapping. DESIGN: A prospective consecutive study (Canadian Task Force classification II-2). SETTING: An academic research center. PATIENTS: Consecutive patients with a pathologic diagnosis of early-stage EC scheduled for primary laparoscopic-assisted staging surgery (laparoscopic hysterectomy, bilateral salpingo-oophorectomy, or comprehensive lymphadenectomy). INTERVENTIONS: Enrolled patients underwent laparoscopic SLN mapping with a 50-mg CNP tracer injection. Fifty patients received fundal subserosal injections at 4 sites (the fundal group), whereas 65 patients received cervical submucosal injections at 2 sites (the cervical group). After SLN mapping, all patients underwent laparoscopic staging surgery. MEASUREMENTS AND MAIN RESULTS: No allergic reactions to CNPs were observed in either group. The overall SLN detection rates were 100% and 92% in the cervical and fundal groups, and the bilateral SLN detection rates were 97% and 68% (p < .001), respectively. A total of 12 metastatic SLNs were accurately detected in 5 patients. The sensitivity of metastatic lymph node detection was 100% in the cervical group, which is higher than that in the fundal group (80%). The false-negative rates were 0% and 20%, respectively, in the cervical and fundal groups. Furthermore, we verified 3 uterine lymphatic pathways using the 2 injection methods. The upper paracervical pathway was the most common drainage pathway in both groups (91.4% in the cervical group vs 80.24% in the fundal group), whereas the infundibulopelvic pathway was observed only in the fundal group (15.11%). CONCLUSION: SLN mapping by CNPs in laparoscopic surgery for EC is a safe and effective alternative, with a higher detection rate and better accuracy with cervical injections than fundal injections. The upper paracervical pathway was the most common lymphatic pathway, whereas the infundibulopelvic pathway was only displayed in fundal injections.

Neoadjuvant Bleomycin, Etoposide, and Cisplatin (BEP) Chemotherapy in the Treatment of Extensively Advanced Yolk Sac Tumors: A Single Center Experience.

OBJECTIVE: This study aimed to investigate the role of neoadjuvant bleomycin, etoposide, and cisplatin (BEP) regimen in patients with extensively advanced yolk sac tumors (YSTs). METHODS: Between July 1982 and December 2015, a total of 58 patients with YST were initially treated at our institution, among which 18 were evaluated to be inoperable and received neoadjuvant BEP regimen. They were either too debilitated by the disease [Eastern Cooperative Oncology Group Performance Status Scale (ECOG ps) ≥2] to undergo a major surgery or were with too extensively disseminated lesions to be optimally debulked. This cohort of patients was retrospectively reviewed. RESULTS: One or 2 cycles of BEP regimen were prescribed to the majority of patients preoperatively. At the completion of neoadjuvant chemotherapy, 17 of them had ECOG ps of 1 or less. Seventeen (94.4%) exhibited clinical partial tumor regression, and 1 (5.6%) had clinical stable disease. Pathological complete tumor regression was observed in 2 (11.1%) patients, whereas the remaining 16 (88.9%) had nearly complete pathological regression. Seventeen patients were cytoreduced to no macroscopic residual disease; the remaining 1 was cytoreduced to macroscopic residual disease of 2 cm or less. No major surgical complications occurred. After a median follow-up of 83.5 months, 17 patients were free of recurrence. Five-year disease-free survival and overall survival were both 94.4%. Fertility-sparing surgery was carried out in all the 17 patients with the desire to preserve their fertility, and 5 infants were delivered in 6 patients who attempted conception. CONCLUSIONS: One or 2 cycles of neoadjuvant BEP regimen followed by cytoreductive surgery offer a chance for cure in extensively advanced patients with YSTs and help pave the way for fertility-sparing surgery.

Pazopanib Maintenance Therapy in East Asian Women With Advanced Epithelial Ovarian Cancer: Results From AGO-OVAR16 and an East Asian Study.

OBJECTIVE: The recent phase 3 trial AGO-OVAR16 demonstrated that pazopanib maintenance improved median progression-free survival in patients with ovarian cancer whose disease did not progress during first-line treatment. However, this improvement was not seen in the subset of East Asian patients. The current analysis evaluated the efficacy and safety of pazopanib maintenance in East Asian patients from AGO-OVAR16 and a separate East Asian study. MATERIALS AND METHODS: East Asian patients from AGO-OVAR16 (n = 209) and the East Asian study (N = 145) were randomized 1:1 to receive pazopanib 800 mg/d or placebo for up to 24 months. The primary end point for each study was progression-free survival by RECIST (Response Evaluation Criteria in Solid Tumors) based on investigator assessment. Clinical and genetics data were analyzed separately by study or pooled according to separate predetermined statistical plans. RESULTS: Pazopanib maintenance had a detrimental effect on median progression-free survival versus placebo in East Asian patients from the combined studies (n = 354; 17.9 vs 21.5 months; hazard ratio, 1.114; 95% confidence interval, 0.818-1.518; P = 0.4928). Pazopanib maintenance showed a disadvantage in overall survival in East Asian patients from AGO-OVAR16 versus placebo (hazard ratio, 1.706; 95% confidence interval, 1.010-2.883; P = 0.0465); overall survival analysis was not performed in the East Asian study because of insufficient event numbers. Pazopanib-treated patients had a significantly higher incidence of grade 3 or higher hypertension (27%) and neutropenia (13%) versus placebo. CONCLUSIONS: The treatment effect of maintenance pazopanib in East Asian patients seemed to differ from that in non-Asian patients. In study-specific and pooled analyses, none of the potential factors analyzed could satisfactorily explain the different efficacy results of pazopanib in East Asian patients.

[Relationship between P53 Protein Expression and Prognosis of Advanced Ovarian Serous Adenocarcinoma].

OBJECTIVE: To study the expression of P53 protein in the advanced ovarian serous adenocarcinoma and explore its potential correlation with the clinicopathological features and prognosis of ovarian cancer. METHODS: The immunohistochemical staining was used to detect the expression of P53 protein in 183 patients with advanced ovarian serous adenocarcinoma. The correlation of P53 protein with the clinicopathological features and its significance in the assessment of prognosis were explored. RESULTS: The P53 protein expression was positive in 62.8% of the patients. Chi-square test showed that the overexpression of P53 protein was positively correlated with the elevation of serum CA125 and the two-tier grading of ovarian serous adenocarcinoma (P<0.001, P=0.038). Univariate analysis suggested that the prognosis of patients was associated with two-tier grading (P=0.007), lymph node metastasis (P=0.036), preoperative serum CA125 level (P=0.002), and P53 overexpression (P<0.001). Multivariate analysis showed that the International Federation of Gynecology and Obstetrics stage (P=0.038), lymph node metastasis (P=0.002), and overexpression of P53 (P=0.001) were independent prognostic factors. CONCLUSION: The P53 protein expression is closely related to the prognosis of advanced ovarian serous adenocarcinoma and can be used as an important indicator for predicting the prognosis.

The role of probiotics in women's health: An update narrative review.

Probiotics, live microorganisms that confer health benefits to the host when administered in adequate amounts, have gained considerable attention for their potential role in maintaining women's health. This overview summarizes key clinical findings on the beneficial effects of probiotics in various aspects of women's health. Probiotics, particularly Lactobacillus species, contribute to vaginal health by promoting a balanced vaginal microbiome to prevent infections and maintain an acidic environment. In gynecologic conditions, probiotics show potential in preventing and managing bacterial vaginosis, vulvovaginal candidiasis, and sexually transmitted infections. Probiotic supplementation has also been associated with improvements in metabolic parameters and menstrual irregularities in polycystic ovary syndrome patients. During pregnancy, probiotics may be helpful in reducing the risk of gestational diabetes, maternal group B streptococcal colonization, obstetric anemia, and postpartum mastitis. In recent years, the potential role of probiotics in the prevention and management of gynecologic cancer has gained attention. Further research is needed to better understand the specific mechanisms and determine the optimal Lactobacillus strains and dosages regimens for gynecologic cancer prevention and therapy. In conclusion, probiotics offer a non-invasive and cost-effective approach to support women's health and prevent obstetric and gynecologic complications.

Diabetic Macular Edema Is Predictive of Renal Failure in Patients With Diabetes Mellitus and Chronic Kidney Disease.

CONTEXT: Chronic hyperglycemia in patients with diabetes mellitus (DM) causes retinal damage and leakage, resulting in vision loss. Although diabetic retinopathy (DR) and diabetic kidney disease (DKD) are usually correlated, the relationship between diabetic macular edema (DME) and DKD remains unknown. OBJECTIVE: To assess whether DME presence can predict renal failure in patients with DM and chronic kidney disease (CKD). METHODS: This retrospective cohort study used data from 120 healthcare organizations in the TriNetX network. Electronic medical records of approximately 90 million patients were reviewed. The study population was classified into DME and non-DME cohorts. Primary and secondary outcomes were new-onset end-stage renal disease (ESRD) and all-cause mortality, respectively. Covariate factors were incorporated to reduce confounding effects. RESULTS: Before matching, the DME cohort used more medication and had poorer renal function and blood sugar control than the non-DME cohort. Subsequently, the 2 groups were well-matched in demographics, socioeconomic status, lifestyle, comorbidities, and medication usage. The DME cohort had a significantly higher risk of ESRD, dialysis, and renal transplantation than the non-DME cohort. Subgroup analyses showed consistent results irrespective of follow-up duration, initial estimated glomerular filtration rate, or glycated hemoglobin levels. Additionally, the DME cohort had a lower risk of all-cause mortality than the non-DME cohort. CONCLUSION: Statistically significant 5-year increased risks of ESRD, dialysis, and renal transplantation were observed in patients with concurrent DME. Therefore, close monitoring and follow-up of the renal function in DM patients with DME are necessary and strongly recommended.

[Clinical analysis for 18 cases of vulvar Bowen's disease].

OBJECTIVE: To analyse the clinical and pathological characteristics, diagnosis, treatment and prognosis of vulvar Bowen's disease. METHODS: Clinical data including pathological characteristics, diagnosis, treatment methods and follow-up of 18 cases with vulvar Bowen's disease admitted to Cancer Hospital, Chinese Academy of Medical Sciences during January 1991 to June 2011 were retrospectively analyzed. RESULTS: The median age of the 18 patients was 37 years (range:23 to 64 years) . Sixteen patients had symptoms of vulvar itching and two patients had no symptom. Five cases were single neoplasm focus and the other 13 cases were multiple focuses. The diagnosis of vulvar Bowen's disease was according to the pathological diagnosis. Its diagnostic characteristic was giant round or ovoid cells with mono nucleolus in the whole layer of epidermis. All the patients received operation, eleven with simple vulvectomy and other seven cases with lumpectomy. The median follow-up time was 123 months (range: 5 to 197 months). Relapse was found in two cases. One patient relapsed five months postoperation and received vulvectomy. Another patient relapsed fifteen moths post-operation and received lumpectomy again. And they were follow-up for 192 months and 55 months respectively after second operation without relapse. CONCLUSIONS: The diagnostic characteristic of vulvar Bowen's disease is giant round or ovoid cell with mono nucleolus in the whole layer of epidermis, itsdiagnosis is according to the pathological diagnosis. Operation could get very good curative effect for patients with primary vulvar Bowen's disease and even for the recurrent patients. The prognosis of vulvar Bowen's disease is good.

[Prognostic analysis of radical radiotherapy in stage Ib and IIa cervical carcinoma].

OBJECTIVE: To investigate the efficacy and prognostic factors in patients with stage Ib and IIa cervical carcinoma by radical radiotherapy. METHODS: Between January 1999 and January 2012, 108 patients with stage Ib and IIa cervical carcinoma received radical radiotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were included and analyzed retrospectively. Patients of stage Ib1, Ib2, IIa1 and IIa2 were 18 (16.7%, 18/108), 38 (35.2%, 38/108), 33 (30.6%, 33/108) and 19 (17.6%, 19/108), respectively. RESULTS: The 5-year overall survival rate was 76.2% and the 5-year disease free survival rate was 75.6%. Totally 25 (23.1%, 25/108) patients developed recurrent disease, 16 of them (64%, 16/25) had local recurrences, 6 (24%, 6/25) had distant metastases and 3 cases had both local recurrence and distant metastases. Among patients with recurrent disease, 23 died and 2 survive with tumor. Totally 24 patients died, 23 of them died due to tumor recurrence and the other one died of other reason. The univariate analysis showed that, lymph node metastasis, squamous cell carcinoma antigen (SCC) levels before treatment, SCC levels after treatment 1 month had relation with overall survival time in patients with stage Ib and IIa cervical carcinoma (all P < 0.05). The multivariate analysis showed that, lymph node metastasis and SCC levels after treatment 1 month were the independent prognostic factors for overall survival time for the cervical squamous cell carcinoma (OR = 2.5, 4.4; all P < 0.05). CONCLUSIONS: By means of radical radiotherapy, stageIb and IIa cervical carcinoma patients with lymph node metastasis and SCC levels ≥ 1.5 mg/L after treatment one month have poor prognosis.While, stageIb and IIa patients with concurrent chemoradiotherapy after neoadjuvant chemotherapy did not affect the prognosis. The 5-year survival rate with concurrent chemoradiotherapy was higher than that of radiotherapy.

[Clinical analysis of 44 cases with malignant transformation of ovarian mature cystic teratoma].

OBJECTIVE: To analyze the clinicopathologic characteristics, treatment and prognostic factors in malignant transformation of mature cystic teratoma (MCT) of ovary. METHODS: The clinical data of 44 patients with MCT from January 1961 to June 2009 were reviewed. RESULTS: The median age of the 44 patients was 48 years (range, 16 - 84 years). Mean tumor size was (16 ± 6) cm. Thirty-two cases were diagnosed squamous cell carcinoma (73%, 32/44), and 5 of them with the elevated level of serumal squamous cell antigen (SCC-Ag). Three of 37 cases (8%, 3/37) were identified with malignant transformation in image examinations. Rapid frozen section examination and multiple-location biopsy were performed in 8 cases, and 5 of them were detected with malignant diseases. Twenty-two patients with disease confined within the unilateral ovary (10 with intact capsule, and 12 with ruptured capsule). Diseases extended extra ovaries in the others 22 patients. The median cumulative overall survivals were 126 and 10 months, respectively. The difference between the two groups was significant (P < 0.01). Twenty-seven patients had no residual tumor after primary surgery. The median cumulative overall survivals between the patients with and without residual tumor were 10 and 84 months respectively, and there were significant difference between two groups (P < 0.01). Seven selected patients with malignant disease confined within unilateral ovary underwent fertility-sparing surgery, and 2 cases of them had successful pregnancies and delivery, while other 4 cases with ruptured capsule recurred. CONCLUSIONS: The most common pathology type of malignant transformation in mature cystic teratoma of the ovary is squamous cell carcinoma. Comprehensive pre-operation image examination and tumor marker level detection might be of great help in diagnosis. Tumor extension extraovary and residual tumor after surgery are the most significant poor prognostic factors. Early stage patient with ruptured capsule should be very discreet to choose fertility-sparing surgery.

[Study of the radiotherapy modality for patients with stage IIb-IIIb cervical stump cancer].

OBJECTIVE: To investigate the radiotherapy modality progress of stageIIb-IIIb cervical stump cancer. METHODS: The clinical data of 13 patients with stageIIb-IIIb cervical stump cancer undergoing radiotherapy from January 2000 to April 2012 was reviewed. Before 2006, 8 patients received conventional external beam radiotherapy and brachytherapy.Since 2006, 5 patients received intensity-modulated radiotherapy (IMRT) and brachytherapy. RESULTS: The median survival was 12-139 months. The median overall survivals and disease free survivals in the conventional radiotherapy (CRT) group were 57 months and 50 months, 3 cases of them recurred during 8-19 months and died of tumor progression.While, the median overall survivals and disease free survival in the IMRT group both were 21 months and nobody recurred. In the CRT group, 7 patients suffered toxicities, including 5 patients grade I-II acute rectum reaction, 2 patients grade I bladder reaction; and 3 had grade I-III, late rectum reaction, 2 patients for grade II bladder late reaction.In the IMRT group, toxicities including 1 case grade I acute or late rectum reaction, and no bladder reaction. CONCLUSION: In our experience, the recommended IMRT and interstitial brachytherapy for the selected patients with advanced cervical stump carcinoma may be obtain better tumor dose distribution and more sparing of the organ at risk.

[A prospective study of adenosine triphosphate-tumor chemosensitivity assay directed chemotherapy in patients with recurrent ovarian cancer].

OBJECTIVE: To investigate the efficacy of adenosine triphosphate (ATP)-tumor chemosensitivity assay (TCA) directed chemotherapy in patients with recurrent epithelial ovarian cancer. METHODS: From August 2010 to June 2012, recurrent epithelial ovarian cancer patients were prospectively enrollmented in Cancer Hospital, Peking Union Medical College,Chinese Academy of Medical Sciences.The entry criteria are as follows: (1) Histologically proven to be epithelial ovarian cancer. (2) Patients of recurrent ovarian cancer with bidimensionally measurable tumor, or ascitic or pleural fluid for testing. (3) Karnofsky performance status > 60. (4) A life expectancy of at least more than 6 months.According to patients desires, they were assigned into two groups: assay-directed therapy group and physician's-choice therapy group, patients' clinical and pathological characteristics, response rate to chemotherapy and progression-free survival (PFS) were compared between two groups. RESULTS: A total of 113 patients with recurrent epithelial ovarian cancer were prospectively enrollmented to assay-directed chemotherapy (n = 56) or physician's-choice chemotherapy (n = 57).There was no difference in median age,types of recurrence, surgical-pathological stage, pathological type, tumor grade, times of recurrence, residual disease at secondary cytoreductive surgery between assay-directed group and physician's-choice group. The overall response rate (ORR) and median PFS in the ATP-TCA group was 66% (37/56) and 7 months, while the ORR in the control group was 46% (26/57, P = 0.037), the median PFS was 4 months (P = 0.040). For platinum-resistant patients, the ORR between ATP-TCA directed chemotherapy 59% (16/27) and control group 25% (7/28) were significantly different (P = 0.010), and the median PFS between two groups were also significantly different (5 months and 2 months, respectively, P = 0.003). CONCLUSION: ATP-TCA directed chemotherapy could improve ORR and PFS in patients with recurrent epithelial ovarian cancer, especially in platinum-resistant patients.

[Clinical analysis of the recurrence of early stage bulky cervical carcinoma].

OBJECTIVE: To analyze the clinical characteristics, influencing factors and outcome of recurrent patients with early stage bulky cervical carcinoma. METHODS: Between January 1(st) 2000 and December 31(st) 2009, 76 patients with stage Ib2 and IIa2 bulky cervical carcinoma developed recurrence and (or) metastasis. The recurrence time, recurrence location, recurrence-related factors, treatment and survival were analyzed. RESULTS: The median follow up was 44 months (9-137 months). The overall recurrence and (or) metastasis rate was 22.6%. The 1-, 1-2, 3-5 and 5-year recurrence and (or) metastasis rates were 38.2%, 27.6%, 30.3% and 3.9%, respectively. The 5-year survival rate of local recurrence was 34.5%, that of distant metastasis was 23.6%, and that of distant metastasis with synchronous pelvic recurrence was 11.1%, (P = 0.555). The 5-year survival rate of patients who received surgery plus chemotherapy, radiation plus chemotherapy and chemotherapy alone after recurrence and (or) metastasis were 53.3%, 30.7% and 24.6%, respectively (P = 0.686). Univariate analysis demonstrated that tumor recurrence and (or) metastasis in patients of the stage Ib2 and IIa2 bulky cervical carcinoma were influenced by the disease stage, pelvic lymph node metastasis, deep cervical stromal invasion, lymphovascular tumor thrombus and pathological types. Multivariate regression analysis demonstrated that pelvic lymph node metastasis, lymphovascular tumor thrombus and pathological types were the key factors affecting the recurrence and (or) metastases of the stage Ib2 and IIa2 bulky cervical carcinoma. Subgroup analysis showed that pelvic lymph node metastasis and stage were the main factors affecting the local recurrence in those patients, and the pathological type, vascular tumor thrombus and pelvic lymph node metastasis were the main factors affecting the distant metastasis. CONCLUSIONS: Recurrence and(or) metastasis of early stage bulky cervical cancer are mostly happened within 2 years post operation. Patients with pelvic lymph node metastasis have high probability to develop local recurrence and distant metastasis. Patients with non-squamous cell carcinoma and lymphovascular tumor thrombus are more likely to develop distant metastasis. Neoadjuvant chemotherapy does not decrease local recurrence and distant metastasis in patients with stage Ib2 and IIa2 bulky cervical carcinoma. Individualized treatment is advised for recurrent patients.

[The mRNA expression of BRCA1, ERCC1, TUBB3, PRR13 genes and their relationship with clinical chemosensitivity in primary epithelial ovarian cancer].

OBJECTIVE: To evaluate the expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA and their relationship with clinical chemosensitivity in primary ovarian cancer, and to assess the predictive value of joint detection of both BRCA1 and ERCC1 genes for the treatment of primary ovarian cancer. METHODS: Primary epithelial ovarian tumor samples were collected from 46 patients who underwent cytoreductive surgery. Real-time quantitative PCR was used to analyze the relative expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA in those cases. The correlation of clinical chemosensitivity and the test results was statistically analyzed. The efficacy of the joint prediction of clinical chemosensitivity by combining the two drug resistance gene detection was evaluated. RESULTS: The BRCA1 mRNA relative expression logarithm in the clinical-resistant group was 0.673±2.143, and clinical-sensitive group -1.436±2.594 (P=0.008). The ERCC1 mRNA relative expression logarithm in the clinical-resistant group was -0.529±1.982 and clinical-sensitive group -3.188±2.601 (P=0.001). BRCA1 and ERCC1 expression level is negatively correlated with platinum-based chemosensitivity. The PRR13 expressions in the two groups were not significantly different (P=0.074), and the TUBB3 expressions between the two groups were also not significantly different (P=0.619). When the intercept point value BRCA1 mRNA expression logarithm was -0.6, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 73.3%, 75.0%, 84.6% and 60.0%, respectively, with the best comprehensive assessment. When the intercept point value of ERCC1 mRNA expression logarithm was -1, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 80.0%, 68.8%, 82.8% and 64.7%, respectively, with the best comprehensive assessment. The combination detection of BRCA1 and ERCC1 can improve the chemotherapeutic sensitivity, specificity, positive predictive value and negative predictive value to 86.7%, 68.8%, 83.9% and 73.3%, respectively. CONCLUSIONS: BRCA1 and ERCC1 mRNA expression has a negative correlation with the clinical sensitivity of platinum-based chemotherapy. Combination detection of the two drug-resistance associated genes can improve the predictive efficacy of ovarian cancer chemosensitivity and beneficial to individual treatment of ovarian cancer.

[Comparative analysis of neoadjuvant therapies in stage Ib2 and IIa2 cervical carcinoma].

OBJECTIVE: To compare the clinical efficacy of neoadjuvant chemotherapy plus vaginal intracavitary irradiation, neoadjuvant chemotherapy alone and vaginal intracavitary irradiation alone followed by radical hysterectomy in patients with stage Ib2 and IIa2 bulkly cervical carcinoma. METHODS: Between January 2000 and December 2009, 224 patients with stage Ib2 and IIa2 bulkly cervical carcinoma (tumor diameter > 4 cm) received neoadjuvant therapy combined surgery in Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences were respectively analyzed, and they were divided into 3 groups according to the preoperative neoadjuvant therapy, the neoadjuvant chemotherapy combined vaginal intracavitary irradiation group (chemotherapy combined irradiation group, n = 86), the neoadjuvant chemotherapy alone group (chemotherapy group, n = 48), the vaginal intracavitary irradiation alone group (irradiation group, n = 90). The efficacy, postoperative risk factors, postoperative adjuvant therapy and survival were compared among the 3 groups. RESULTS: Among the chemotherapy combined irradiation group, chemotherapy group and irradiation group, the response rate (RR) were respectively 62% (53/86), 42% (20/48) and 37% (33/90), and there was significant difference (P = 0.003). The comparison of deep stromal invasion, lymph node metastases, lympho-vascular space involvement (LVSI) and other risk factors among the 3 groups, which showed that there were no statistically significant differences (P > 0.05). In chemotherapy combined irradiation group, the percentage of stromal invasion ≥ 1/2 was lower than that in chemotherapy group [53% (46/86) vs. 73% (35/48), P = 0.027], and the percentage of lymph node metastases was significantly lower than irradiation group [17% (15/86) vs. 29% (26/90), P = 0.046], and the risk factors-free rate was significantly higher than chemotherapy group [44% (38/86)vs. 25% (12/48), P = 0.028]. Among the chemotherapy combined irradiation group, chemotherapy group and irradiation group, the percentage of postoperative radiation therapy were respectively 47% (40/86), 67% (32/48) and 62% (56/90), and the differences were statistically significant (P = 0.035). The five-year disease free survival (DFS) was 79%, 75% and 78%, respectively. The five-year overall survival (OS) was respectively 81%, 78% and 81% among 3 groups, and there were no statistically significant differences (P > 0.05). Among 224 patients, the five-year DFS of the patients with 0, 1 and ≥ 2 risk factors after surgery were 90%, 75% and 57%, and OS were 95%, 82% and 65%, and there were no statistically significant differences (P < 0.01, respectively). Of patients without postoperative risk factors, the five-year OS in those without receiving postoperative radiation therapy was 96%, while 89% in received postoperative radiation therapy patients, there were no statistically significant differences (P = 0.263). CONCLUSION: There are no differences of DFS and OS among the neoadjuvant chemotherapy combined vaginal intracavitary irradiation group, the neoadjuvant chemotherapy alone group and the vaginal intracavitary irradiation alone group patients with stage Ib2 and IIa2. Patients without risk factors after neoadjuvant therapies have better prognosis.

[Analysis of 25 cases of brain metastasis from gynecological cancers].

OBJECTIVE: To discuss the clinical characteristics, treatment and prognostic factors of brain metastasis from gynecological cancers. METHODS: Clinical records of 25 brain metastasis patients from gynecological cancers admitted from January 1999 to January 2009 were reviewed retrospectively. The curative effects of different treatments were compared. The prognostic factors were determined using the Cox regression model. RESULTS: There were 14 cases ovarian malignant tumor, 6 cases cervical carcinoma and 5 cases uterine malignant tumor. Seven cases (28%, 7/25) had solitary metastatic lesion in the brain. Extracranial metastases were detected in 18 cases (72%, 18/25). Five patients only received one kind of treatment, and the mean survival time was 4.0 months (0.5 to 9.5 months). Sixteen patients received combined treatment, 3 of them received combined treatment including surgery, and the mean survival time was 8.4 months (4.1 to 13.4 months); 13 of them received chemotherapy and radiotherapy, and the mean survival time was 14.2 months (4.3 to 58.1 months). Four patients received only palliative supportive care, and the survival time was only 0.1 to 1.0 month. The Cox regression model showed that Karnofsky performance status scale, with or without extracranial metastases and the treatment method were the independent prognostic factors of brain metastasis from gynecological cancers (P < 0.05). CONCLUSION: The incidence of brain metastasis from gynecological cancers is low and the prognosis is very poor. Combined treatments may get better effects.

[Primary leiomyosarcoma of the vagina: a clinical analysis of 9 cases].

OBJECTIVE: To analyze the clinical characteristics, diagnoses, treatments and prognoses of vaginal leiomyosarcoma (LMS). METHODS: The clinical and pathological recordings of 9 patients suffering from vaginal leiomyosarcoma from January 1973 to May 2011 were analyzed retrospectively. RESULTS: The study group constituted 2.7% (9/330) of all the malignant vaginal tumor admitted to our hospital in the same period. The major clinical manifestations were asymptomatic vaginal mass (3/9), bellyache and vaginal bleeding (2/9), vaginal pain (2/9), and difficulty in defecation (1/9) and micturition (1/9). Preoperative diagnosis was highly unreliable. Based on the sample chose, the diagnosis were made in 3 cases by preliminary biopsy before undertaking surgery, while 6 cases were confirmed shortly after simple tumor excision or unexpected recurrence. All the patients were pathologically confirmed diagnosis by tumor resection specimen or biopsy, 5 cases of them were also confirmed by virtue of immunohistochemistry staining. All 9 patients, 8 cases received initial surgery, four of them patients received postoperative adjuvant chemotherapy or radiation therapy, the remaining 1 patients received initial chemotherapy and radiotherapy. Follow-up was performed for all the 9 patients, of which 3 cases were lost, the median follow-up time was 50 months (range 7 - 134). Four patients underwent local recurrence and adjacent organ metastases within two years, with 5 years survival rate 4/9. CONCLUSIONS: Primary vaginal leiomyosarcoma is a rare and difficult to diagnose preoperatively tumor. In this regard, It is strongly recommend preoperative biopsy for definitive diagnosis and perform surgery as the principal approach, in conjunction with radiotherapy or chemotherapy when needed to improve survival.