| Objective:Firstly,to evaluate the clinical outcome of borderline ovarian tumor(BOT)patients,including pregnancy,recurrence and survival and to assess related risk factors.Secondly,to evaluate the sensitivity and positive predictive value(PPV)of intra-operative frozen section(FS)diagnosis in BOTs,and to explore the factors affecting the diagnostic accuracy.Furthermore,we perform a Meta-analysis to verify it.We hope our study could offer beneficial support to the diagnosis and treatment of BOT patients.Methods:We performed a retrospective study of all patients diagnosed as BOT through FS or paraffin section(PS)at Qilu Hospital between January 2005 and December 2015.Clinical and pathologic data were extracted.Patients were followed-up by telephone for the clinical outcome and pregnancy outcome.The follow-up was ended on August 2016.Statistical analysis was constructed to describe the data and to evaluate the statistical significance of related risk factors.Chi-square was performed for enumeration data,t test was performed for category data.Kaplan-Meier estimates were used to assess the progression free survival(PFS)and overall survival(OS),and to describe survival curve.We have searched the Pubmed,PMC,Medline and Cochrane database for literature review.Meta-analysis was performed with Review Manager 5.3 software.Results:Totally,there were 164 patients included in our retrospective study.The median age at diagnosis was 41 years old(range 13-86 years old).77 patients(47%)were?40 years old.Comprehensive surgical staging and fertility sparing surgery(FSS)were performed in 54.9%(n=90)and 45.1%(n=74)of patients respectively.130 patients had stage I disease(79.2%).The most common type of BOT was mucinous(50.6%),followed by serous(43.9%).CA125 and CA19-9 levels were increased in 102(62.2%)and 41(25%)patients,respectively.The median postoperative follow-up was 41 months(range 9-136 months).There were 74 patients who received FSS,of which 68 patients attempted to conceive,and 14 patients achieved pregnancy,the cumulative pregnancy was 16.The total pregnancy rate was 18.9%with 13.3%for unilateral cystectomy(UC),25%for unilateral salpingo-oophorectomy(USO),8.3%for bilateral cystectomy(BC)and 18.2%for unilateral salpingo-oophorectomy + contralateral cystectomy(USO+CC)respectively.Age(p=0.036),endometriosis(p=0.031)were associated with fertility outcome.Meanwhile,different kinds of FSS,FIGO stage,histology and chemotherapy were not statistically significant with fertility outcome.The overall recurrence rate was 4.9%(n=8).Advanced FIGO stage(p<0.001),histology(p<0.001),chemotherapy(p=0.006),and invasive implants(p=0.006)played an important role on recurrence.Meanwhile,age,CA125,cyst rupture,tumor size,bilateral disease,micro-papillary,microinvasion,peritoneal washing and noninvasive implants were not significant statistically.There were seven deaths,including five patients died of disease per se,which indicating the overall death rate was 4.3%.Three-and Five-year PFS rates were 94%and 89%,respectively.Kaplan-Meier curve showed that chemotherapy(p=0.02),mucinous histology(p=0.006),and micro-invasion(p=0.041)were related to the PFS.While elevated CA125,FIGO stage,cyst rupture,hysterectomy,appendectomy,omentectomy,pelvic/para-aortic lymphadenectomy,bilateral tumor,micro-papillary,invasive or non-invasive implants,intraepithelial carcinoma and CA19-9 were not statistically significant with PFS of BOT patients.Three-and Five-year OS rates of BOT patients were 97%and 93%.Recurrence(p<0.001),age(p=0.01),and menopause(p=0.026)were related to the OS.Other factors,such as chemotherapy,histology,micro-invasion,elevated CA125,FIGO stage and so on,were not statistically significant with OS of BOT patients.There were nine patients,who were unavailable to get the information of frozen section diagnosis,excluded in the study regarding frozen section diagnosis accuracy.Eventually,155 patients were included.Agreement between FS and PS diagnosis was observed in 127/155(81.9%)patients,yielding a sensitivity of 92.7%and a PPV of 87.6%.Under-diagnosis and over-diagnosis occurred in 22 cases(14.2%)and 6 cases(3.9%),respectively.In our univariate analysis of our retrospective study,surgery approach(p=0.024)and tumor size(p=0.048)were significantly associated with misdiagnosis.There was no statistical significance of clinical outcome such as extent of surgery(p=0.838),recurrence(p=0.586),fertility(p=0.560),death(p=0.362)between misdiagnosed and accurately diagnosed BOT patients.The Meta-analysis of frozen section diagnosis accuracy of BOT patients,including 13 studies with 1,577 patients,indicated that the accuracy(69.2%),sensitivity(82.5%),and PPV(81.1%)were low;under-diagnosis(20.2%)and over-diagnosis(10.5%)were frequent.The meta-analysis results showed that mucinous histology(p<0.0001,OR=2.03[1.47-2.81])and unilateral tumors(p=0.001,OR=2.39[1.41-4.06])were associated with the misdiagnosis of BOT.In our retrospective study,there was no statistical significance of clinical outcome such as extent of surgery(p=0.838),recurrence(p=0.586),fertility(p=0.560),death(p=0.362)between misdiagnosed and accurately diagnosed BOT patients.Conclusion:BOT patients had an excellent prognosis.Fertility sparing surgery could be performed for young women who want to preserve their fertility ability.USO tended to have a better pregnancy outcome than other type of conservative surgery.Advanced FIGO stage,histology,chemotherapy and invasive implants were associated with high recurrence.Mucinous histology,chemotherapy and micro-invasion were related to the PFS.While age,menopause and recurrence were related to the OS.Diagnosis accuracy of FS of BOT patients differ from different medical institutions obviously.Mucinous BOT and unilateral tumor were related with misdiagnosis,which need our special attention when making surgery decision. |
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