Heat-responsive microRNAs participate in regulating the pollen fertility stability of CMS-D2 restorer line under high-temperature stress.

Anther development and pollen fertility of cytoplasmic male sterility (CMS) conditioned by Gossypium harknessii cytoplasm (CMS-D2) restorer lines are susceptible to continuous high-temperature (HT) stress in summer, which seriously hinders the large-scale application of "three-line" hybrids in production. Here, integrated small RNA, transcriptome, degradome, and hormone profiling was performed to explore the roles of microRNAs (miRNAs) in regulating fertility stability in mature pollens of isonuclear alloplasmic near-isogenic restorer lines NH and SH under HT stress at two environments. A total of 211 known and 248 novel miRNAs were identified, of which 159 were differentially expressed miRNAs (DEMs). Additionally, 45 DEMs in 39 miRNA clusters (PmCs) were also identified, and most highly expressed miRNAs were significantly induced in SH under extreme HT, especially four MIR482 and six MIR6300 family miRNAs. PmC28 was located in the fine-mapped interval of the Rf1 gene and contained two DEMs, gra-miR482_L-2R + 2 and gma-miR2118a-3p_R + 1_1ss18TG. Transcriptome sequencing identified 6281 differentially expressed genes, of which heat shock protein (HSP)-related genes, such as HSP70, HSP22, HSP18.5-C, HSP18.2 and HSP17.3-B, presented significantly reduced expression levels in SH under HT stress. Through integrating multi-omics data, we constructed a comprehensive molecular network of miRNA-mRNA-gene-KEGG containing 35 pairs of miRNA/target genes involved in regulating the pollen development in response to HT, among which the mtr-miR167a_R + 1, tcc-miR167c and ghr-miR390a, tcc-miR396c_L-1 and ghr-MIR169b-p3_1ss6AG regulated the pollen fertility by influencing ARF8 responsible for the auxin signal transduction, ascorbate and aldarate metabolism, and the sugar and lipid metabolism and transport pathways, respectively. Further combination with hormone analysis revealed that HT-induced jasmonic acid signaling could activate the expression of downstream auxin synthesis-related genes and cause excessive auxin accumulation, followed by a cascade of auxin signal transduction, ultimately resulting in pollen abortion. The results provide a new understanding of how heat-responsive miRNAs regulate the stability of fertility restoration for CMS-D2 cotton under heat stress.

Dose effects of restorer gene modulate pollen fertility in cotton CMS-D2 restorer lines via auxin signaling and flavonoid biosynthesis.

KEY MESSAGE: Dose effects of Rf1 gene regulated retrieval mechanism of pollen fertility for CMS-D2 cotton. Cytoplasmic male sterility conditioned by Gossypium harknessii cytoplasm (CMS-D2) is an economical pollination control system for producing hybrid cotton seeds compared to artificial and chemical emasculation methods. However, the unstable restoring ability of restorer lines is a main barrier in the large-scale application of "three-line" hybrid cotton in China. Our phenotypic investigation determined that the homozygous Rf1Rf1 allelic genotype had a stronger ability to generate fertile pollen than the heterozygous Rf1rf1 allelic genotype. To decipher the genetic mechanisms that control the differential levels of pollen fertility, an integrated metabolomic and transcriptomic analysis was performed at two environments using pollen grains of four cotton genotypes differing in Rf1 alleles or cytoplasm. Totally 5,391 differential metabolite features were detected, and 369 specific differential metabolites (DMs) were identified between homozygous and heterozygous Rf1 allelic genotypes with CMS-D2 cytoplasm. In addition, transcriptome analysis identified 2,490 differentially expressed genes (DEGs) and 96 unique hub DEGs with dynamic regulation in this comparative combination. Further integrated analyses revealed that several key DEGs and DMs involved in indole biosynthesis, flavonoid biosynthesis, and sugar metabolism had strong network linkage with fertility restoration. In vitro application of auxin analogue NAA and inhibitor Auxinole confirmed that over-activated auxin signaling might inhibit pollen development, whereas suppressing auxin signaling partially promoted pollen development in CMS-D2 cotton. Our results provide new insight into how the dosage effects of the Rf1 gene regulate pollen fertility of CMS-D2 cotton.

Integrated analysis of metabolome and transcriptome reveals the cytoplasmic effects of CMS-D2 on pollen fertility resulting from disrupted lipid metabolism.

Using cytoplasmic male sterility of Gossypium harknesii (CMS-D2) is an economical and effective method to produce cotton hybrids. However, the detrimental cytoplasmic effects of CMS-D2 on pollen fertility and fiber yields greatly limit the further development of three-line hybrid cotton in China. In this study, an integrated non-targeted metabolomics and transcriptome analysis was performed on mature pollens of maintainer line NB, isonuclear alloplasmic near-isogenic restorer lines NH and SH under two environments. A total of 820 metabolites were obtained, of which lipids and lipid-like molecules were the most, followed by organic acids derivatives, phenylpropanoids, and polyketides. Transcriptome analysis revealed significantly more differentially expressed genes (DEGs) in SH versus NH both in Anyang and Jiujiang, and most of the DEGs were significantly upregulated. Further KEGG analysis showed that most DEGs were enriched in the biosynthesis of unsaturated fatty acids, phenylalanine metabolism, and phagosome. Based on the weighted gene co-expression network analysis, totally 74 hub genes were also identified, of which three transcription factors, i.e., WRKY22, WRKY53, and ARF18 were significantly upregulated in SH and may play a negative regulatory role in pollen development by directly or indirectly regulating the jasmonic acid synthesis and signal transduction. Moreover, we found that the negative effects of CMS-D2 cytoplasm on pollen fertility were mainly due to disturbed lipid metabolism, especially the metabolic balance of unsaturated fatty acids, ultimately resulting in the decline of pollen fertility. Meanwhile, in the presence of CMS-D2 sterile cytoplasm, the cytoplasmic-nucleus interaction effects generated a substantial quantity of flavonoids involved in the fertility restoration process. This study preliminarily clarified some of the reasons for the negative effects of CMS-D2 cytoplasm on pollen fertility, and our results will provide an important theoretical reference for further breeding and improvement of three-line hybrid cotton in the future.

The Phosphofurin Acidic Cluster Sorting Protein 2 (PACS-2) E209K Mutation Responsible for PACS-2 Syndrome Increases Susceptibility to Apoptosis.

Phosphofurin acidic cluster sorting protein 2 (PACS-2) is a multifunctional cytosolic membrane trafficking protein with distinct roles in maintaining cellular homeostasis. Recent clinical reports have described 28 individuals possessing a de novo PACS-2 E209K mutation that present with epileptic seizures and cerebellar dysgenesis. As the PACS-2 E209K missense mutation has become a marker for neurodevelopmental disorders, we sought to characterize its biochemical properties. Accordingly, we observed that the PACS-2 E209K protein exhibited a slower turnover rate relative to PACS-2 wild type (WT) upon cycloheximide treatment in 293T cells. The longer half-life of PACS-2 E209K suggests a disruption in its proteostasis, with the potential for altered protein-protein interactions. Indeed, a regulatory protein in neurodevelopment known as 14-3-3ε was identified as having an increased association with PACS-2 E209K. Subsequently, when comparing the effect of PACS-2 WT and E209K expression on the staurosporine-induced apoptosis response, we found that PACS-2 E209K increased susceptibility to staurosporine-induced apoptosis in HCT 116 cells. Overall, our findings suggest PACS-2 E209K alters PACS-2 proteostasis and favors complex formation with 14-3-3ε, leading to increased cell death in the presence of environmental stressors.

PACS-1 contains distinct motifs for nuclear-cytoplasmic transport and interacts with the RNA-binding protein PTBP1 in the nucleus and cytosol.

Phosphofurin acidic cluster sorting protein 1 (PACS-1) is canonically a cytosolic trafficking protein, yet recent reports have described nuclear roles for PACS-1. Herein, we sought to define the nuclear transport mechanism of PACS-1. We demonstrate that PACS-1 nucleocytoplasmic trafficking is dependent on its interaction with the nuclear transport receptors importin alpha 5 and exportin 1. PACS-1 nuclear entry and exit are defined by a nuclear localization signal (NLS, residues 311-318) and nuclear export signal (NES3, residues 366-375). Mutation of the PACS-1 NLS and NES3 altered the localization of a complex formed between PACS-1 and an RNA-binding protein, polypyrimidine tract-binding protein 1. Overall, we identify the nuclear localization mechanism of PACS-1 and highlight a potential role for PACS-1 in RNA-binding protein trafficking.

Sentinel lymph Node mapping versus systematic pelvic lymphadenectomy on the prognosis for patients with intermediate-high-risk Endometrial Cancer confined to the uterus before surgery: trial protocol for a non-inferiority randomized controlled trial (SNEC trial).

BACKGROUND: Sentinel lymph node (SLN) mapping has been recommended as an alternative staging approach to lymphadenectomy for apparent uterine-confined endometrial cancer (EC). However, the prognostic value of SLN mapping alone instead of systematic lymphadenectomy on EC patients remains unclear. METHODS: A multi-center, open label, non-inferiority randomized controlled trial has been designed to identify if SLN mapping alone is not inferior to pelvic lymphadenectomy on prognosis of patients with intermediate-high-risk EC clinically confined to uterus. Eligible patients will be 1:1 randomly assigned to accept SLN mapping or pelvic lymphadenectomy. The primary endpoint is the 2-year progression-free survival (PFS). The second points are the 5-year PFS, 5-year overall survival, surgery-related adverse events and life quality. A total of 780 patients will be enrolled from 6 hospitals in China within 3-year period and followed up for 5 years. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04276532.

Chiral UiO-MOFs based QCM sensors for enantioselective discrimination of hazardous biomolecule.

Developments of enantioselective devices for discriminating bio-enantiomers is of significant importance. Due to the vital role of Cysteine (Cys) in biological processes and the hazardous effect of its D-enantiomer, discriminating Cys enantiomers without auxiliary enzyme is highly wanted. In this work, a pair of UiO-MOF enantiomers (UiO-tart) have been fabricated through post-modification, which could be further fabricated into enantiomeric sensing devices (UiO-tart@Au). By employing the Quartz Crystal Microbalance (QCM) technology, gravimetric discrimination of Cys enantiomers could be achieved. UiO-tart@Au is highly enantioselective, and the afforded enantioselective factor (5.97 ± 0.54) represents the best performance reported ever. In the fabricated device, MOF layer acts as the chiral selector for specific Cys enantiomer, and the reaction between the captured Cys enantiomer and Au results in the mass growth of the system. Solid-phase extraction (SPE) gives an e.e. value of 71.6 ± 3.8%, substantially confirming the chiral-selector role of UiO-tart. DFT calculations indicate that enantiomeric H-bonding effect and greater reaction enthalpy should be the reason. To the best of our knowledge, this work represents the first example of chiral tartaric acid derived MOF sensors for enantioselective discrimination of Cys, suggesting a promising potential of developing chiral MOFs based devices for enhanced enantioselective application.

Postmodified Dual Functional UiO Sensor for Selective Detection of Ozone and Tandemly Derived Sensing of Al3.

Development of highly sensitive and selective fluorescent sensors toward hazardous analytes represents great progress in fabricating sensing devices for practical applications. In this work, a highly selective sensor with dual functions has been fabricated via facile postmodification of the UiO-MOF. Butene modified salicylaldehyde is covalently linked to the UiO-66 scaffold via an efficient Schiff-base reaction, resulting in a highly fluorescent ozone sensor of UiO-66-butene. Ozonolysis of the terminal olefin followed by ß-elimination could significantly quench the bright blue fluorescence of UiO-66-butene, and linear turn-off detection of ozone in the range of 0-100 µM is well established. The detection is highly sensitive and selective, and a detection limit of 73 nM was calculated. Remarkably, the ozonolysis afforded product could further act as a selective sensor for Al3+ via turn-on fluorescence with a detection limit of 142 nM, representing a second potential sensing function. The chemically selective sequential ozonolysis/ß-elimination and remarkable dual functions offer the exclusive detection of ozone over other oxidative species as well as Al3+ over other cations following a tandem process, representing the first example of a direct MOF sensor for dual sensing of ozone and Al3+. This work demonstrates the potential of employing combinatorial principles for fabricating highly selective sensors, and postmodification of MOFs represents a promising facile strategy for developing various functional sensors.

Surgical and oncological outcomes of an improved nerve-sparing radical hysterectomy technique: 6 years of experience at two centres.

OBJECTIVE: An improved nerve-sparing radical hysterectomy (NSRH), which is based on the paravesico-vaginal space, has been recently introduced in a phase II, prospective clinical trial by our team. This study aims to report the surgical and oncological outcomes of this improved NSRH. METHODS: One hundred seventy-seven consecutive patients were enrolled in our study and underwent the improved NSRH. The proportion of successful catheter removal and postvoid residual urine volume (PVR) of 50 mL or less at postoperative day 7 or day 4 was used to assess surgical outcomes. The local control rate (LCR), disease free survival (DFS), and overall survival (OS) were used to assess oncological outcomes. RESULTS: Postoperative 30-day complications occurred in 27/177 (15.3%) patients. The rate of successful catheter removal and PVR of 50 mL or less were 85.2% (23/27) and 66.7% (18/27) at postoperative day 7, and 73.3% (110/150) and 35.3% (53/150) at postoperative day 4. A total of 13 (7.9%) patients showed recurrence after a median follow-up time of 39.2 months (range 3.2-68.1 months). The estimated 2-year and 5-year DFS rates were 92.2% and 91.1%, respectively. Seven (4.2%) patients presented local recurrence, and five (3.0%) patients were dead at the end of the follow-up period. The estimated 5-year LCR and OS were 95.1% and 96.2%, respectively. In univariate analysis, International Federation of Gynecology and Obstetrics (FIGO) stage, lymphovascular space invasion (LVSI), and lymph node metastasis were found to be the prognostic risk factors of DFS. Patients with LVSI were associated with a worse DFS according to the multivariate analysis. CONCLUSIONS: The improved NSRH in our study may provide better surgical outcomes without compromising the survival in patients with early cervical cancer.

Comparison of the adipogenesis in intramuscular and subcutaneous adipocytes from Bamei and Landrace pigs.

Fat deposition is a complex process involving proliferation, differentiation, and lipogenesis of adipocytes. Bamei and Landrace are considered to represent fat- and lean-type pig breeds. Subcutaneous (SC) and intramuscular (IM) pre-adipocytes were cultured to compare the proliferation and lipogenesis in these breeds. The differentiated adipocytes were exposed to glucose or insulin to evaluate their effects on lipogenesis and lipogenic gene expression. Pre-adipocytes proliferated dramatically faster in SC vs. IM cells, and in Bamei vs. Landrace breeds. Lipogenesis and lipogenic gene expression had a greater increase in Bamei than in Landrace, and in SC vs. IM in the process of differentiation. Glucose markedly promoted lipogenesis and lipogenic gene expression in differentiated adipocytes. The stimulation of high-glucose levels on lipogenesis and ChREBP and lipogenic gene expression was higher in SC than IM adipocytes, and in Bamei vs. Landrace. Insulin largely increased SREBP-1c expression, however it modestly stimulated lipogenesis and lipogenic gene expression, and there was no difference between cell populationsor between breeds. These data demonstrated that regional and varietal differences obviously existed in the development of porcine adipocytes. The proliferation and differentiation capacity of pre-adipocytes, and the adipocyte lipogenesis stimulated by glucose, are stronger in Bamei than Landrace, and in SC vs. IM adipocytes independent of breed.

A prospective study of fertility-sparing treatment with megestrol acetate following hysteroscopic curettage for well-differentiated endometrioid carcinoma and atypical hyperplasia in young women.

PURPOSE: To investigate the feasibility and efficacy of curettage with hysteroscopy followed by megestrol acetate (MA) for well-differentiated endometrioid carcinoma (EC) confined to the endometrium and for atypical hyperplasia (AH) in young women. PATIENTS AND METHODS: Fourteen patients with EC and 12 patients with AH were prospectively enrolled in this study. All of the patients received at least 12 weeks of oral MA (160 mg/day) following thorough curettage with hysteroscopy. The response was assessed histologically every 12 weeks. The primary endpoint was the complete response rate. Adverse events, pregnancy rates and recurrence rates were secondary end points. RESULTS: Twenty-one (80.8 %) patients responded to treatment. The median time to response was 12 weeks. After a median follow-up of 32 months, 6 patients had recurrences. Significantly, more patients with infertility or PCOS experienced recurrence (P = 0.040, P = 0.015). Eight patients attempted to conceive after complete response; two spontaneous conceptions and one normal delivery were achieved. No disease-related or treatment-related deaths were observed. CONCLUSIONS: Fertility-sparing treatment with MA following entirely hysteroscopic curettage is effective, demonstrating the least toxicity for rigorously selected young women with well-differentiated EC confined to the endometrium or with AH; however, close follow-up is required for the potential consequences of improper patient selection and a substantial rate of recurrence.

Association between XPF polymorphisms and cancer risk: a meta-analysis.

BACKGROUND: Xeroderma pigmentosum complementation group F (XPF or ERCC4) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. A series of epidemiological studies have examined associations between XPF polymorphisms and cancer risk, but the findings remain inconclusive. METHODOLOGY/PRINCIPAL FINDINGS: In this meta-analysis of 47,639 cancer cases and 51,915 controls, by searching three electronic databases (i.e., MEDLINE, EMBASE and CNKI), we summarized 43 case-control studies from 29 publications on four commonly studied polymorphisms of XPF (i.e., rs1800067, rs1799801, rs2020955 and rs744154), and we did not find statistical evidence of any significant association with overall cancer risk. However, in stratification analyses, we found a significant association of XPF-rs1799801 with a reduced cancer risk in Caucasian populations (4,845 cases and 5,556 controls; recessive model: OR=0.87, 95% CI=0.76-1.00, P=0.049, P=0.723 for heterogeneity test, I(2) =0). Further genotype-phenotype correlation analysis showed that the homozygous variant CC genotype carriers had higher XPF expression levels than that of the TT genotype carriers (Student's t test for a recessive model: P=0.046). No publication bias was found by using the funnel plot and Egger's test. CONCLUSION: This meta-analysis suggests a lack of statistical evidence for the association between the four XPF SNPs and overall risk of cancers. However, XPF-rs1799801 may be associated with cancer risk in Caucasian populations, which needs to be further validated in single large, well-designed prospective studies.

A risk model for secondary cytoreductive surgery in recurrent ovarian cancer: an evidence-based proposal for patient selection.

BACKGROUND: To develop a risk model for predicting complete secondary cytoreductive surgery (SCR) in patients with recurrent ovarian cancer. METHODS: Individual data of 1075 patients with recurrent ovarian cancer undergoing SCR from 7 worldwide centers were pooled and analyzed. The risk model was developed based on the factors impacting on SCR surgical outcome. Additional data on 117 patients who were not included in the development of the model were used for external validation and to assess the discrimination of the model. RESULTS: Of the 1075 patients, 434 (40.4%) underwent complete resection. Complete secondary cytoreduction was associated with six variables: FIGO stage (odds ratio [OR] = 1.32, 95% confidence interval [95% CI]: 0.97-1.80), residual disease after primary cytoreduction (OR = 1.69, 95% CI: 1.26-2.27), progression-free interval (OR = 2.27, 95% CI: 1.71-3.01), Eastern Cooperative Oncology Group (ECOG) performance status (OR = 2.23, 95% CI: 1.45-3.44), CA125 (OR = 1.85, 95% CI: 1.41-2.44), and ascites at recurrence (OR = 2.79, 95% CI: 1.88-4.13). These variables were entered into the risk model and assigned scores ranging from 0 to 11.9. Patients with total scores of 0-4.7 were categorized as the low-risk group, in which the proportion of complete cytoreduction was 53.4% compared with 20.1% in the high-risk group (OR = 4.55, 95% CI: 3.43-6.04). In external validation, the sensitivity and specificity was 83.3% and 57.6%, respectively. Area under the curve of the receiver-operating characteristics for predicting complete SCR was 0.68 (95% CI: 0.60-0.79). CONCLUSIONS: This model and scoring system may well predict the outcome of SCR and could potentially be useful in future clinical trials to determine which patients with recurrent ovarian cancer should have SCR as part of their management.

Surgery in recurrent epithelial ovarian cancer: benefits on Survival for patients with residual disease of 0.1-1 cm after secondary cytoreduction.

AIMS: Recent retrospective trials stated that a benefit of surgery for recurrent ovarian cancer may be limited to patients in whom a complete cytoreduction (R0) could be achieved. Most of them pointed out there was no difference in survival between residual disease of 0.1-1 cm (R1) and >1 cm (R2). The aim of this study was to evaluate survival benefits from cytoreduction to R1. METHODS: Between 2002 and 2006, 123 patients with recurrent epithelial ovarian cancer undergoing secondary cytoreduction were identified from tumor registry databases. RESULTS: The median age at recurrence was 51 years (range: 28-84). Fifty-one (41.5%) patients had R0, 46 (37.4%) patients had R1, and 26 (21.1%) patients had R2 resection. The median survival of the entire cohort was 31.7 months, with an estimated 5-year survival of 31.1%. The median survival and estimated 5-year survival for patients with R1 were 31.1 months and 23.9%, and there were significant differences in survival when compared to 15.6 months and 6.4% in R2 (chi(2) = 7.45, P = 0.006), 63.2 months (mean survival) and 54.4% in complete cytoreduction (chi(2) = 8.93, P = 0.0028). CONCLUSIONS: Complete secondary cytoreduction is the strongest survival determinant in recurrent epithelial ovarian cancer, whereas patients with residual disease of 0.1-1 cm may also benefit from secondary cytoreduction.

Weekly induction intraperitoneal chemotherapy after primary surgical cytoreduction in patients with advanced epithelial ovarian cancer.

BACKGROUND: Traditional intraperitoneal (IP) therapy administered simultaneously with intravenous (IV) chemotherapy in the primary setting has been well documented. This retrospective study was conducted to investigate the role of weekly IP therapy as an inducing intervention before front-line IV chemotherapy, particularly in patients with bulky residual disease after surgery. METHODS: A total of 426 patients with advanced ovarian cancer treated between 1990 and 1999, were reviewed. Follow-up data were available in 409 patients. Of whom, 230 patients received postoperative weekly IP therapy with a median cycles of 4, other 179 patients who did not receive any IP therapy were used as the control group. RESULTS: The median age of the patients was 51 years (range, 20-77 years). One hundred eighty-nine patients with stage III disease and 41 patients with stage IV disease were treated with postoperative IP therapy, respectively. Complications and toxicity were observed in 68 patients (29.5%), but there were no grade 4 toxicities and no patients died of complications or toxicities. In patients with residual disease > 1 cm, the median survival of those with IP delivery of chemotherapy and those without was 21.6 months and 18.8 months, respectively (hazard ratio [HR]= 0.69, P = 0.02). Whereas, in patients with residual disease

[Multidisciplinary therapy after radical surgery in stage I b1-II b cervical cancer patients with positive lymph nodes].

OBJECTIVE: To study the modality of multidisciplinary therapy and prognosis of cervical cancer patients with positive lymph nodes after radical surgery. METHODS: From January 1990 to June 2003, 215 patients with clinical stage I b1-II b node-positive cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy and were histologically confirmed to have lymph node involvement were analyzed. These patients were divided into four groups as chemoradiotherapy group (107 cases), radiotherapy group (45 cases), chemotherapy group (22 cases) and no adjuvant therapy group (41 cases). The prognosis and potential prognostic variables of the four groups were studied by survival analysis. RESULTS: The 3-year disease-free survival (DFS) rate of the chemoradiotherapy group, chemotherapy group, radiotherapy group and no adjuvant therapy group were 60.7%, 53.5%, 47.4% and 36.0% respectively. The 3-year DFS rate of the chemoradiotherapy group was significantly higher than that of the no adjuvant therapy group (P = 0.001). However, the 3-year DFS rate of the chemotherapy group, radiotherapy group were not significantly higher than that of the no adjuvant therapy group (P = 0.060 and 0.159). Among the four groups, the pelvic recurrent rate of the chemoradiotherapy group (7.5%) was much lower than those of the other three groups (22.7%, 26.7%, 34.1%, respectively; P < 0.01). However, the distant metastases rate did not decrease significantly (16.8%, 18.2%, 15.6%, 22.0%, respectively; P > 0.05), neither did the distant metastasis with pelvic recurrent rate (P > 0.05). COX proportional hazard model analysis showed that tumor size, histological type, the number of positive lymph node and postoperative adjuvant therapy were independent survival predictors of the patients with positive lymph node (P < 0.05). CONCLUSION: Chemoradiotherapy after radical surgery significantly improves the 3-year DFS, and decreases the pelvic recurrence in the cervical cancer patients with positive lymph node.

Recurrent ovarian carcinoma of low malignant potential: the role of secondary surgical cytoreduction and the prognosis in Chinese patients.

BACKGROUND AND OBJECTIVES: The study of pathology and prognosis for patients with ovarian tumors of low malignant potential (LMP) has been well documented. The treatment, particularly the secondary surgery, for recurrent disease is less documented. This study was conducted to investigate the role of secondary surgical cytoreduction for recurrent ovarian carcinoma of LMP. METHODS: Patients with ovarian carcinoma of LMP at advanced stages experiencing disease recurrence and treated by secondary surgical cytoreduction at Fudan University Cancer Hospital were retrospectively reviewed. RESULTS: Sixteen patients with recurrent serous and mucinous ovarian LMP tumors who underwent secondary surgical cytoreduction were entered in this study. The median age was 46.5 years. The 5-year survival in those with residual disease < or =1 cm after secondary surgical cytoreduction was 83%, compared to 26% in those with residual disease >1 cm (P = 0.01). Multivariate analysis suggested that extent of recurrent disease (solitary vs. multiple, relative risk [RR] =2.69, P < 0.01), and residual disease after secondary surgical cytoreduction (< or =1 cm vs. >1 cm, RR = 2.56, P < 0.01) were determinants of survival. CONCLUSIONS: For recurrent ovarian carcinomas of low malignant potential, prolonged survival was observed in patients with solitary recurrent disease and optimal secondary surgical outcome.

[Multidisciplinary treatment of recurrent epithelial ovarian carcinoma and prognostic analysis].

OBJECTIVE: To investigate individualized and multi-phase management of recurrent epithelial ovarian carcinoma in order to improve survival of the patients. METHODS: From 1998 to 2002, 70 patients with recurrent epithelial ovarian carcinoma were enrolled in the present study. The treatments were divided into: (1) Induction of tumor remission: platinum sensitive patients were treated with paclitaxol + cisplatin (TP) or carboplatin + cyclophosphamide (CP) regimen; platinum resistant patients used Taxol + mitomycin (TM) or etoposide + mitomycin (VM) regimen. Resection of tumors was done in an attempt to reduce the residual tumor with a diameter less than 1 cm. Local radiotherapy was performed for those with residual tumor and who achieved clinical response after chemotherapy or surgery. (2) Consolidation therapy: chemotherapy with lower doses was administrated after disease remission. Interferon was used as immunotherapy during chemotherapy and radiotherapy. Survival analysis was done. RESULTS: (1) The 1, 2, 3, 4, 5-year survival rates were 67%, 51%, 45%, 38%, 32%. Median survival was 38.57 months. (3) The 1, 2, 3-year progression-free survival rates of the research arm were 41%, 37%, 24%. Median progression-free survival was 12.00 months. (4) Multivariate analysis revealed that platinum-free interval (P < 0.05), Karnofsky performance scale (P < 0.01), residual disease (P < 0.01) and courses of second-line chemotherapy (P < 0.05) were independent prognostic factors. Residual disease (P < 0.05) and courses of second-line chemotherapy (P < 0.01) contributed to progression-free survival. CONCLUSIONS: Individualized and multi-phase treatment of recurrent epithelial ovarian carcinoma is efficacious. Optimal second cytoreduction and second-line chemotherapy are beneficial to improve the survival.

Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: who benefits?

BACKGROUND: This study was performed to address patient selection criteria and the role of secondary cytoreductive surgery (SCR) in patients with epithelial ovarian carcinoma (EOC) who had relapsed tumors after a progression-free interval > or = 3 months. METHODS: One hundred seventeen patients with relapsed EOC after a clinical complete remission duration > or = 3 months who underwent SCR were entered on this prospective trial. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using log-rank tests, logistic stepwise regression analyses, and a Cox stepwise regression model. RESULTS: The median patient age at the time of relapse was 53 years (range, 20-78 years). The median survival was 22 months and the estimated 5-year survival rate for the entire cohort was 17.2%. Tumor was confined to a solitary site in 33 patients and to > or = 2 sites in 84 patients. After they underwent SCR, 11 patients were rendered macroscopically disease free, 61 patients had residual disease that measured < or = 1 cm in greatest dimension, and 45 patients had bulky intraabdominal residual disease. Survival was influenced by the extent of relapse disease (solitary site vs. multiple sites; P < 0.0001), the size of residual disease after SCR (0 cm vs. < or = 1 cm [P = 0.1211], < or = 1 cm vs. > 1 cm [P = 0.0002], and 0 cm vs. > 1 cm [P = 0.0011]), Eastern Cooperative Oncology Group performance status (0 vs. 1 [P = 0.134], 1 vs. 2 [P = 0.007], and 0 vs. 2 [P = 0.0012]), and the number of cycles of salvage chemotherapy (1-2 cycles vs. 3-5 cycles [P = 0.0144]; 1-2 cycles vs. > or = 6 cycles [P < 0.0001]; and 3-5 cycles vs. > or = 6 cycles [P = 0.0009]). The outcome of SCR was influenced by the extent of relapse disease (multiple sites [51.2%] vs. solitary sites [87.9%]; relative risk [RR] = 9.1237; P = 0.0002) and by the use of bowel resection (yes [60.9%] vs. no [37.5%]; RR = 0.3828; P = 0.0106). CONCLUSIONS: SCR was found to be safe for patients with relapsed EOC who achieved a clinical complete remission that lasted > or = 3 months, with resectability similar to that of primary debulking surgery. Optimal surgical outcomes were achieved easily in patients who apparently had solitary tumor sites, with bowel resection making it possible to remove bulky tumors that involved the intestine. A survival benefit was provided by optimal SCR, particularly when surgery was supported by multiple courses of salvage chemotherapy.