Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

HSA_CIRC_0004050 on proliferation and apoptosis of A549 cells through ERK/JNK signaling pathway.

The aim of this study was to screen the differentially expressed circular ribonucleic acid (circRNA) in non-small cell lung cancer (NSCLC) and explore its functional mechanism. Differentially expressed circRNAs in tumor tissues of NSCLC patients were detected via gene microarray and reverse transcriptionquantitative polymerase chain reaction (RT-qPCR). The associaton between their expressions and the clinical phenotypes was explored combined with clinical data. The effect of overexpression of hsa_circ_0004050 on the proliferation of A549 cells was detected via cell counting kit-8 (CCK-8) assay and CFSE assay. The effect of overexpression of hsa_circ_0004050 (human circular ribonucleic acid_0004050) on the apoptosis of A549 cells was detected using the Annexin V-FITC/PI kit. Then the direct-acting miRNAs of hsa_circ_0004050 were screened using bioinformatics software and luciferase reporter assay, and the direct targets of miR- 1233-3p were explored using bioinformatics software and luciferase reporter assay combined with RTqPCR and Western blotting. The effects of overexpression of miR-1233-3p or knockdown of dual specificity phosphatase 9 (DUSP9) on the cell proliferation and apoptosis affected by overexpression of hsa_circ_0004050 were detected. Western blotting was performed to detect the effects of hsa_circ_0004050 on the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK) signaling pathway. The expression of hsa_ circ_0004050 was significantly lower in tumor tissues than that in para-carcinoma tissues in NSCLC patients. The expression of hsa_circ_0004050 was significantly correlated with TNM stage, tumor size and lymph node metastasis. The results of survival analysis showed that the survival time of patients with a high expression of hsa_circ_0004050 was obviously prolonged. According to the results of phenotype assay, hsa_circ_0004050 could promote apoptosis and inhibit proliferation of A549 cells. In terms of its mechanism, hsa_circ_0004050 could markedly increase the protein expression of DUSP9 via targeting miR-1233-3p in A549 cells, thereby inhibiting the ERK/JNK signaling pathway. Hsa_circ_0004050 may serve as a potential therapeutic target for NSCLC or a biomarker for the diagnosis of NSCLC in the future.

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: recurrent disease.

This manuscript reports the consensus statements regarding recurrent ovarian cancer (ROC), reached at the fifth Ovarian Cancer Consensus Conference (OCCC), which was held in Tokyo, Japan, in November 2015. Three important questions were identified: (i) What are the subgroups for clinical trials in ROC? The historical definition of using platinum-free interval (PFI) to categorise patients as having platinum-sensitive/resistant disease was replaced by therapy-free interval (TFI). TFI can be broken down into TFIp (PFI), TFInp (non-PFI) and TFIb (biological agent-free interval). Additional criteria to consider include histology, BRCA mutation status, number/type of previous therapies, outcome of prior surgery and patient reported symptoms. (ii) What are the control arms for clinical trials in ROC? When platinum is considered the best option, the control arm should be a platinum-based therapy with or without an anti-angiogenic agent or a poly (ADP-ribose) polymerase (PARP) inhibitor. If platinum is not considered the best option, the control arm could include a non-platinum drug, either as single agent or in combination. (iii) What are the endpoints for clinical trials in ROC? Overall survival (OS) is the preferred endpoint for patient cohorts with an expected median OS < or = 12 months. Progression-free survival (PFS) is an alternative, and it is the preferred endpoint when the expected median OS is > 12 months. However, PFS alone should not be the only endpoint and must be supported by additional endpoints including pre-defined patient reported outcomes (PROs), time to second subsequent therapy (TSST), or time until definitive deterioration of quality of life (TUDD).

Protein and mRNA expression of follicle-stimulating hormone receptor and luteinizing hormone receptor during the oestrus in the yak (Bos grunniens).

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) have a central role in follicle growth, maturation and oestrus, but no clear pathway in the seasonal oestrus of yak (Bos grunniens) has been found. To better understand the role of FSH and LH in seasonal oestrus in the yak, six yaks were slaughtered while in oestrus, and the pineal gland, hypothalamus, pituitary gland, and gonads were collected. Using real-time PCR and immunohistochemical assays, we determined the mRNA and protein expression of the FSH and LH receptors (FSHR and LHR) in these organs. The analysis showed that the FSHR mRNA expression level was higher in the pituitary gland tissue compared with LHR (p < .01) during oestrus. By contrast, there was low expression of FSHR and LHR mRNA in the pineal gland and hypothalamus. FSHR mRNA expression was higher than that of LHR (p < .05) in the ovary, whereas LHR mRNA expression was higher than that of FSHR (p < .01) in the uterus. FSHR and LHR proteins were located in the pinealocyte, synaptic ribbon and synaptic spherules of the pineal gland and that FSH and LH interact via nerve fibres. In the hypothalamus, FSHR and LHR proteins were located in the magnocellular neurons and parvocellular neurons. FSHR and LHR proteins were localized in acidophilic cells and basophilic cells in the pituitary gland, and in surface epithelium, stromal cell and gland epithelium in the uterus. In the ovary, FSHR and LHR protein were present in the ovarian follicle. Thus, we concluded that FSHR and LHR are located in the pineal gland, hypothalamus, pituitary and gonad during oestrus in the yak. However, FSHR was mainly expressed in the pituitary gland and ovaries, whereas LHR was mainly expressed in the pituitary gland and uterus.

[Analysis of prognostic factors for patients with stageâ b non-small cell lung cancer after operation].

Objective: To study the prognostic factors for patients with stage ⅠB non-small cell lung cancer (NSCLC) after radical operation (R0). Methods: The clinical data of 458 patients who underwent radical resection for NSCLC and were pathologically diagnosed with stage ⅠB lung cancer from January 2009 to December 2010, were reviewed retrospectively. Those cases include 269 male patients and 189 female, aged between 28 and 88, with a median age of 61 years. The Kaplan-Meier method and Log rank test were used for univariate survival analysis and the Cox proportional hazards model for multivariate survival analysis. Results: Among these 458 cases, 66 patients were dead and the 5-year survival rate was 85.6%.The results of the univariate analysis showed that the age ≥65 years, elevated preoperative CEA, preoperative FEV1%pred<70%, vascular carcinoma embolus, and low tumor differentiation were associated with poor prognosis of patients(P<0.05). The results of the multivariate analysis showed that elevated preoperative CEA, preoperative FEV1%pred<70% and low tumor differentiation were connected with poor prognosis of patients (P<0.05). Conclusions: Elevated preoperative CEA, preoperative FEV1%pred<70% and low tumor differentiation are independent risk factors which influence prognosis and survival rate of patients with stage ⅠB NSCLC, among which those with poorly differentiated tumor could benefit from postoperative chemotherapy.

[Comparative analysis of the role of CD4(+) and CD8(+) T cells in severe asthma development].

The role of CD8^(+) T cells in asthma has not been fully discussed. The mechanisms of CD4^(+) and CD8^(+) cells in severe asthma (SA) development were compared. The microarray data (GSE31773) was downloaded from the Gene Expression Omnibus (GEO) database, including 20 samples of CD4^(+) and CD8^(+) T cells, which were collected from 8 health controls (HC), 4 non-severe asthma (NSA) and 8 SA patients. DEGs of CD4^(+) and CD8^(+) T cells in the HC vs. NSA and HC vs. SA groups were identified using the limma package in R. GO and pathway enrichment analysis of the common DEGs between the two groups were analyzed using DAVID. The interactive network of DEGs and significant modules were further explored. In CD4^(+) cells, there were 168 DEGs in HC vs. NSA group and 685 DEGs in HC vs. SA group, while for CD8^(+) T cells there were 719 DEGs in the HC vs. NSA groups and 1255 DEGs in the HC vs. SA groups. Besides, 80 common DEGs from CD4^(+) samples were enriched in the MAPKKK cascade and molecular metabolism, and 385 common DEGs of CD8^(+) T cells were significantly related with cell apoptosis and transformation. Moreover, two significant modules of DEGs in CD4^(+) were found to be involved with MPO and BPI. One module of CD8^(+) T cells containing PDHA1 and MRPL42 was identified to be related with glycolysis. In conclusion, MPO and BPI in CD4^(+), and PDHA1 and MRPL42 in CD8^(+) T cells might be used as specific biomarkers of SA progression. Therapy targeting the functions of CD4^(+) and CD8^(+) T cells may provide a novel perspective for SA treatment.

Predictors of survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery based on the pooled analysis of an international collaborative cohort.

BACKGROUND: This study aims to identify prognostic factors and to develop a risk model predicting survival in patients undergoing secondary cytoreductive surgery (SCR) for recurrent epithelial ovarian cancer. METHODS: Individual data of 1100 patients with recurrent ovarian cancer of a progression-free interval at least 6 months who underwent SCR were pooled analysed. A simplified scoring system for each independent prognostic factor was developed according to its coefficient. Internal validation was performed to assess the discrimination of the model. RESULTS: Complete SCR was strongly associated with the improvement of survival, with a median survival of 57.7 months, when compared with 27.0 months in those with residual disease of 0.1-1 cm and 15.6 months in those with residual disease of >1 cm, respectively (P<0.0001). Progression-free interval (≤23.1 months vs >23.1 months, hazard ratio (HR): 1.72; score: 2), ascites at recurrence (present vs absent, HR: 1.27; score: 1), extent of recurrence (multiple vs localised disease, HR: 1.38; score: 1) as well as residual disease after SCR (R1 vs R0, HR: 1.90, score: 2; R2 vs R0, HR: 3.0, score: 4) entered into the risk model. CONCLUSION: This prognostic model may provide evidence to predict survival benefit from secondary cytoreduction in patients with recurrent ovarian cancer.

MicroRNA-124 inhibits proliferation and metastasis of esophageal cancer via negatively regulating NRP1.

This paper presents several inaccuracies and mistakes. Therefore, the article "MicroRNA-124 inhibits proliferation and metastasis of esophageal cancer via negatively regulating NRP1, by R.-K. Zang, J.-B. Ma, Y.-C. Liang, Y. Wang, S.-L. Hu, Y. Zhang, W. Dong, W. Zhang, L.-K. Hu, published in Eur Rev Med Pharmacol Sci 2018; 22 (14): 4532-4541-DOI: 10.26355/eurrev_201807_15508-PMID: 30058693" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15508.

MicroRNA-487a promotes proliferation of esophageal cancer cells by inhibiting p62 expression.

OBJECTIVE: MicroRNAs are endogenous, non-coding, small RNAs that can regulate biological processes. Previous studies have found that microRNA-487a serves as an oncogene. However, the role of microRNA-487a in esophageal cancer (EC) has not been reported. The aim of this investigation was to investigate the biological role of microRNA-487a in EC and its underlying mechanism. PATIENTS AND METHODS: The expression of microRNA-487a in 65 pairs of EC tissues and para-cancerous tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Chi-square test was used to analyze the relationship between microRNA-487a expression with age, sex, clinical stage and distant metastasis of OS patients. Kaplan-Meier survival analysis was conducted to evaluate the correlation between microRNA-487a expression and prognosis of EC patients. Subsequently, microRNA-487a expression in EC cell lines was detected as well. After microRNA-487a knockdown, cell counting kit-8 (CCK-8), EdU and transwell assay were conducted to evaluate the role of microRNA-487a in the biological performances of EC cells, respectively. Meanwhile, the apoptosis of EC cells was determined using flow cytometry. Finally, the interaction between microRNA-487a and p62 was explored by Western blot. Transwell assay was carried out in EC cells co-transfected with p62 overexpression plasmid and si-microRNA-487a. RESULTS: Compared with para-cancerous tissues, microRNA-487a expression was significantly higher in EC tissues, and the difference was statistically significant. MicroRNA-487a was highly expressed in EC cells as well. Low expression of microRNA-487a was positively correlated with clinical stage, whereas was not correlated with age, sex, lymph node metastasis and distant metastasis of EC patients. Kaplan-Meier survival curves showed that high expression of microRNA-487a was markedly associated with poor prognosis of EC. The knockdown of microRNA-487a significantly inhibited proliferative, migratory and invasive abilities of EC cells but induced cell apoptosis. Western blot results showed that the protein expression of p62 was remarkably upregulated after microRNA-478a knockdown in EC cells. Transwell assay demonstrated that co-transfection with overexpression plasmid of p62 and si-microRNA-487a in EC cells markedly decreased invasive and migratory abilities. CONCLUSIONS: MicroRNA-487a is highly expressed in EC and is closely correlated with clinical stage and poor prognosis of EC. Our findings confirm that microRNA-487a promotes malignant progression of EC by regulating p62 expression.

Concurrent chemotherapy and adjuvant extended field irradiation after radical surgery for cervical cancer patients with lymph node metastases.

The purpose of this retrospective study was to report our experience with concurrent chemotherapy and adjuvant extended field irradiation after radical surgery for cervical carcinoma patients with common iliac node and/or multiple pelvic lymph nodes metastases. We studied 25 patients with FIGO stage IB-IIB (IB, 3; IIA, 15; and IIB, 7) cervical carcinoma who underwent radical surgery and had histologically confirmed involvement of common iliac nodes and/or multiple (>or=2) pelvic lymph nodes. These patients received the first cycle of systemic chemotherapy 2 weeks after radical surgery. Then, they received pelvic and extended field irradiation (40-45 Gy) with weekly cisplatinum (30 mg/m(2)). They were then given five more cycles of consolidation chemotherapy. Survival curves were generated by the Kaplan-Meier method. The 3-year progression-free survival (PFS) and overall survival rates were 63% and 76%, respectively. The PFS rates with multiple pelvic node and common iliac node metastases were 69% and 61%, respectively. The pelvic recurrence rate was 8% (2/25) and that for distant metastases was 32% (8/25). No patient's treatment failed in the para-aortic region. The median interval from the surgery to the recurrence was 14 months (range, 5-29 months). Nineteen (76%) patients experienced grades 1-2 and four (16%) experienced grades 3-4 neutropenia. Fifteen patients (60%) experienced grades 1-2 and one (4%) experienced grades 3-4 gastrointestinal toxicity. Concurrent chemotherapy and adjuvant extended field irradiation after radical surgery achieved good local control with acceptable toxicity. However, subsequent distant metastasis was still the predominant form of treatment failure even after consolidation chemotherapy.

MicroRNA-124 inhibits proliferation and metastasis of esophageal cancer via negatively regulating NRP1.

OBJECTIVE: MicroRNAs are a kind of endogenous, non-coding RNAs, which exert a significant role in pathological processes. Previous studies have reported that microRNA-124 is a tumor suppressor. The specific effect of microRNA-124 on esophageal cancer, however, has not been fully elucidated. This study aims to explore the role of microRNA-124 in esophageal cancer and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-124 expressions in 75 esophageal cancer tissues, paracancerous tissues, and esophageal cancer cell lines were detected by qRT-PCR (quantitative Real-Time Polymerase Chain Reaction). The relationship between microRNA-124 expression, clinical progression, pathological indicators, and prognosis of patients with esophageal cancer was analyzed. For in vitro experiments, we performed CCK-8 (cell counting kit-8), colony formation and transwell assay to detect cell proliferation, migration, and invasion abilities after microRNA-124 overexpression in TE-1 and EC-109 cells, respectively. Western blot was utilized to explore the regulatory role of microRNA-124 in esophageal cancer cells. RESULTS: MicroRNA-124 was downregulated in esophageal cancer tissues than that of paracancerous tissues. Patients with esophageal cancer who had lower expression level of microRNA-124 presented higher tumor stage and metastasis incidence, as well as lower survival rate. In vitro studies demonstrated a decreased cell proliferation and migration abilities after microRNA-124 overexpression. Western blot results showed upregulated PI3K and AKT, and downregulated PTEN in esophageal cancer cells after overexpression of microRNA-124. Furthermore, microRNA-124 was confirmed to negatively regulate NRP1, so as to participate in the development of esophageal cancer. CONCLUSIONS: MicroRNA-124 is downregulated in esophageal cancer tissues, which is remarkably correlated to the development, pathological grade, and poor prognosis of esophageal cancer. Overexpressed microRNA-124 is capable of inhibiting the malignant progression of esophageal cancer via negatively regulating NRP1.

Microarray expression profiling of dysregulated long non-coding RNAs in Hirschsprung's disease reveals their potential role in molecular diagnosis.

BACKGROUND: Hirschsprung's disease (HSCR) is one of the common digestive disorders in the new born. Long non-coding RNAs (lncRNAs) play an important role in various biological processes. However, knowledge on lncRNAs in HSCR is limited. METHODS: The expression profile of lncRNAs in HSCR was obtained using microarray. A total of 2078 differentially expressed lncRNAs were detected by microarray in HSCR tissues compared with matched normal colon tissues (fold change ≥2, p < 0.05). Candidate biomarkers were selected from these differentially expressed lncRNAs based on artificial criterion (raw signal intensity ≥50; fold change ≥8) and then validated in 80 pairs of HSCR and normal tissues using quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the computational analysis was used to evaluate the lncRNA-microRNA and lncRNA-protein relationships. KEY RESULTS: A panel of 5-lncRNAs was identified to distinguish HSCR from normal tissues with remarkable sensitivity and specificity. The area under the receiver operating characteristic curve (AUC) for HSCR identification in the validation set was 0.875. The bioinformatics analysis reveals that these dysregulated lncRNAs are mainly involved in RNA-protein relationships, including RNA splicing, binding, transport, processing, and localization. CONCLUSIONS & INFERENCES: Our results are the first to report the expression profile of dysregulated lncRNAs in HSCR and infer that lncRNAs may serve as novel diagnostic biomarkers for HSCR.

Impact of secondary cytoreductive surgery on survival of patients with advanced epithelial ovarian cancer.

AIMS: To investigate the impact on survival of secondary cytoreduction for advanced epithelial ovarian cancer and variables influencing redebulking surgical outcome. METHODS: Between 1986 and 1997, 106 patients who received secondary cytoreductive surgery and consequent second-line chemotherapy for stages III and IV epithelial ovarian cancer were retrospectively reviewed. The optimal residual disease cut-off was 1.0 cm. The Cox proportional regression model and logistic stepwise regression were used in statistical processing of the data. RESULTS: The median age of the patients was 50 years (range, 26-77 years). Optimal secondary cytoreduction was achieved in 46 of 106 patients (43.4%). There was a significant difference in survival between patients who were optimally cytoreduced compared to those suboptimaly cytoreduced, with an estimated median survival in the optimal group of 20 months vs 8 months in the suboptimal group ((2)=42.03, P=0.0000). When factorized, patients had significant survival benefit from optimal secondary cytoreduction for recurrent disease and interval cytoreduction. Survival was adversely influenced by progression-free interval < or =12 months (P=0.0078), residual disease >1 cm (P=0.0001) and presence of refractory ascites (P=0.0001). The probability of successful redebulking surgery was affected by presence of refractory ascites (P=0.0023) in all 106 patients and by the ascites (P=0.0072) and residual disease at initial operation in recurrent disease (P=0.0096). CONCLUSION: Secondary surgical cytoreduction surgery significantly lengthened survival for patients with recurrent epithelial ovarian cancer or those receiving interval cytoreduction. Patients with refractory ascites, however, were not suitable for aggressive secondary surgery, and redebulking surgery for those with residual disease of >1.0 cm after primary operation should be considered prudently in recurrent disease.

Epithelial ovarian cancer presenting initially with extraabdominal or intrahepatic metastases: a preliminary report of 25 cases and literature review.

The purpose of this study was to investigate the clinical features of patients with epithelial ovarian cancer (EOC) that are initially categorized as extraabdominal adenocarcinoma of unknown primary. Twenty-five patients with EOC, who were treated in the Cancer Hospital of Shanghai Medical University from January 1986 to December 1997, and manifesting as extraperitoneal or liver parenchyma metastases at the time of presentation without detectable ovarian tumors, were retrospectively studied. Sixteen patients (64%) were optimally surgical debulked. When compared with 52 other women with stage IV EOC, 20 patients who initially sought treatment for extraabdominal metastases experienced a better prognosis, with an estimated median survival of 24 months versus 10 months (p = 0.0427). The median survival was 30 months in patients with pleural effusion or supraclavicular lymph node metastases versus 19 months in those with spread to other sites (p = 0.0264). The prognosis of such cases, mainly for those with supraclavicular lymphadenopathy or malignant pleural effusion, is better than that for other stage IV EOC patients, probably because most of the patients who initially had distant metastases were generally in condition that permitted aggressive surgery or multicycle chemotherapy.

The safety and efficacy of the Isola Spinal Implant System for the surgical treatment of degenerative disc disease. A prospective study.

STUDY DESIGN: This is a prospective study designed in consultation with and approved by the Food and Drug Administration with the purpose of determining the safety and efficacy of the Isola Spinal Implant System for the surgical treatment of patients with degenerative disc disease. OBJECTIVES: To report the results of the degenerative disc disease group from the Isola Investigational Device Exemption study, which was done to determine whether the Isola Spinal Implant System is a safe and effective treatment. SUMMARY OF BACKGROUND DATA: The safety and efficacy of transpedicular instrumentation as an adjunct in achieving lumbar spine fusion are still debated. METHODS: Hospital Investigational Review Board approval of the study protocol was obtained at the 10 participating centers. One hundred twenty patients (49 men and 71 women; average age, 54 years [range, 25-83 years]) were enrolled. Clinical and radiographic follow-up evaluation was done using protocols established prospectively. RESULTS: Of the 120 patients, 12 (10%) had device-related problems. There were two operative and four device related complications after surgery. Six other patients had their implants removed either for local pain (two) or for looseness or breakage (four). Of 118 patients eligible for follow-up evaluation at 24 months, 107 (91%) were available for study. Fusion was achieved in 97 (91%) patients. Average combined function and pain scores improved by 2.6 points (P < 0.0001). Clinical success, as measured by combining function and pain scores, was achieved in 65% of the patients by the most stringent criteria and 73% by less stringent criteria. Clinical success was significantly higher in patients who had not had previous surgery than in those who had, 77% versus 57% (P = 0.04). CONCLUSIONS: The present study suggests that the Isola Spinal Implant System can be safely used, is an effective adjunct in the achievement of fusion, and yields an acceptable number of successful clinical outcomes, especially when considering the preponderance of previously operated patients included in this group.

Cytoreductive surgery for stage IV epithelial ovarian cancer.

We tried to determine the role of cytoreductive surgery for stage IV epithelial ovarian cancer and in what conditions this surgical procedure could carry the best benefits. From January 1986 to December 1997, seventy-one of 73 patients with stage IV epithelial ovarian cancer who were treated in Cancer Hospital of Shanghai Medical University were retrospectively reviewed. Clinical information including age, grade, histology, presence of ascites, size of residual disease, site of extra-abdominal metastasis, whether initially presenting as metastatic disease or not, neo-adjuvant chemotherapy, platinum-based chemotherapy and second-line chemotherapy was obtained. Survival was calculated by life-table and survival curves were computed using the Kaplan-Meier method with differences in survival estimated by log-rank test. Independent prognostic factors were identified by Cox's proportional hazards regression model. The median age of the patients' population was 54 years (range 22-82), median follow-up time was 12 months (range 3 to 130) and estimated 5-year survival rate 6.1%. Thirty out of 71 (42.3%) patients were successfully debulked (< or = 1 cm) at the time of initial surgery. There was a significant difference in five-year survival rate between patients optimally (14.1%) vs suboptimally (0%) cytoreduced, with an estimated median survival in the optimal group of 23 months vs 9 months in the suboptimal group (P=0.0001, long-rank test). When the variables were factorized, only in patients with malignant pleural effusion or positive supraclavicular lymph nodes, optimal cytoreduction could get the greatest benefits. Multivariate analysis revealed that the size of residual disease and ascites were independent factors of survival. However, only ascites was the prognostic factor of progression-free survival. Optimal cytoreductive surgery is an important determinant of survival in women with stage IV epithelial ovarian cancer, mainly in those with malignant pleural effusion or positive supraclavicular lymph node pathology.

[Pelvic exenteration of advanced gynecological malignacies: a report of 18 cases].

OBJECTIVE: To investigate the role of pelvic exenteration in the treatment of advanced gynecological malignances. METHODS: Eighteen patients with cervical cancer in 8, vulvar cancer in 8, and vaginal cancer in 2, who underwent pelvic exenteration at the Cancer Hospital of Shanghai Medical University between 1970 and 1990 were retrospectively analyzed. RESULT: Median age was 52 years (range 27-65). One woman received surgery of total pelvic exenteration, 10 anterior and 7 posterior exenteration. The 3,5-year survival rates were 72%, 50%, respectively. Postoperative morbidity was 16%, and the surgical mortality was 0%. Bowel obstruction occurred in 2 of 18 cases, one of them was treated surgically. CONCLUSIONS: (1) Patients with advanced central type pelvic neoplasms can be successfully treated with exenteration; (2) The patients should be properly selected prior to and in operation, and the procedures must be performed specifically, particularly in exploration stage.

[Cytoreductive surgery in the management of stage IV epithelial ovarian cancer].

OBJECTIVE: To determine the role of cytoreductive surgery in patients with stage IV epithelial ovarian cancer. METHODS: From Jan. 1986 to Dec. 1997, 71 patients with stage IV epithelial ovarian cancer who were surgically treated in our hospital were retrospectively reviewed. Survival was calculated by Kaplan-Meier method with differences in survival estimated by Log-rank test. Independent prognostic factors were identified by the COX's stepwise regression model. RESULTS: Thirty (42.3%) of 71 patients were successfully debulked (< or = 1 cm) at the time of initial surgery. The estimated 5-year total survival rate was 6.1%. There was a significant difference in survival between patients optimally (13.7%) vs. suboptimally (0.0%) cytoreduced, with an estimated medium survival of 23 months in optimal group vs. 9 months in suboptimal group (P < 0.001). When the variables were factorized, optimal cytoreduction could get the greatest benefit. Only in patients with malignant pleural effusion or positive supraclavicular lymph node. Multivariate analysis revealed that size of residual disease and ascites were independent factors for both overall and progression-free survival (P < 0.05). CONCLUSIONS: Optimal cytoreductive surgery is an important determinant of survival in women with stage IV epithelial ovarian cancer, especially in those with malignant pleural effusion or positive supraclavicular lymph node pathology.

[Ovarian carcinoma presents as distant metastases without detectable tumors of the origin disease at the first presentation].

OBJECTIVE: To study the characteristics, therapies and prognosis of the patients with epithelial ovarian cancer (EOC) that are initially categorized as extra-abdominal adenocarcinoma of unknown primary. METHODS: Twenty-five patients with EOC, who were treated in the Cancer Hospital of Fudan University from Jan. 1986 to Dec. 1997, and manifesting as extra-peritoneal or liver parenchyma metastases at the time of presentation, without detectable ovarian tumors, were retrospectively studied. RESULTS: Supraclavicular and inguinal lymph node metastases were common in this group of patients, with 6 and 5 cases respectively, and 6 patients with more than two sites metastases simultaneously. 16 patients (64%) were optimally surgical debulked. 20 patients with stage IV EOC initially presenting as extra-abdominal metastases experienced a better prognosis, with an estimated median survival of 24 months. Of whom the median survival was 30 months in patients presenting with pleural effusion or supraclavicular lymph node metastases Vs. 19 months in those with other sites spread (P = 0.0264). CONCLUSIONS: The prognosis of such cases, particularly for those with supraclavicular lymphadenopathy or malignant pleural effusion, is a lot better than other stage IV EOC patients, probably because of most of the patients initially presenting with distant metastases being generally in a good condition competent for aggressive surgery or multi-cycle chemotherapy.

[Impacts of chemotherapy on long-term survival of patients with advanced epithelial ovarian cancer].

OBJECTIVE: To investigate the role of first-line chemotherapy in the management of advanced epithelial ovarian cancer (AEOC) and the effects on long-term survival epithelial. METHODS: From January 1986 to December 1997, 348 cases of stage III and IV epithelial ovarian cancer treated at our institute were reviewed retrospectively, and the patients were divided into optimal and suboptimal groups according to the size of residual disease after primary cytoreduction. Survival was calculated by Kaplan-Meier method with difference in survival estimated by Log-rank test. Long-term survival (5 years) determining factors were identified by Logistic regression model. RESULTS: The median age was 55 years (range, 20-82 years). In the optimal group, there was a significant difference in survival between patients with and without intraperitoneal chemotherapy, with an estimated median survival of 46 months and 36 months respectively (chi2 = 7.39, P = 0.0065). In the suboptimal group, the estimated median survival was 22 months in patients with more than 6 cycles of chemotherapy, 11 months in those less than 6 cycles (chi2 = 4.31, P = 0.0380). Neoadjuvant chemotherapy, tumor grade were independent prognostic factors of survival in this group. Size of residual disease, intraperitoneal chemotherapy, and tumor grade were determinants of long-term survival of AEOC. CONCLUSIONS: Multi-courses ( > 6) of platinum-based intravenous chemotherapy prolonged the survival of patients with suboptimal cytoreduction. Intraperitoneal chemotherapy was one of the dominant long-term survival determinants, and mainly on those with size of residual disease less than 1 cm.