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Background: We investigated whether mutations in plasma circulating tumor DNA (ctDNA) can provide prognostic insight in patients with different histological types of ovarian carcinoma. We also examined the concordance of mutations detected in ctDNA samples with those identified in the corresponding formalin-fixed paraffin-embedded (FFPE) tumor specimens., Methods: Between July 2016 and December 2017, 29 patients with ovarian carcinoma were prospectively enrolled. FFPE tumor specimens were obtained from all participants. A total of 187 blood samples for ctDNA analysis were collected before surgery (C0), immediate after surgery before adjuvant chemotherapy (C1), and at six-month intervals. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures., Results: The study cohort consisted of 13 (44.8%) patients with high-grade serous carcinomas (HGSC), 9 (31.0%) with clear cell carcinoma, 2 (6.9%) with mucinous carcinomas, 4 (13.8%) with low-grade serous carcinomas, and 1 (3.4%) with endometrioid carcinoma. Twenty-four (82.8%) patients had at least one detectable ctDNA variant. The concordance rate between mutations identified in pretreatment ctDNA and corresponding FFPE tumor specimens was 92.3% for patients with HGSC and 58.6% for the entire cohort. The median follow-up time was 33.15 months (range: 0.79-46.13 months). Patients with an advanced stage disease more likely had detectable ctDNA mutations before surgery (C0) and after surgery at C1, while those with HGSC more likely had ctDNA mutations detected before surgery. The presence of ctDNA mutations at C1 was an independent predictor of worse OS with a hazard ratio of 6.56 (95% confidence interval, (1.07-40.17) for detectable versus undetectable C1 ctDNA variants, p = 0.042)., Conclusions: ctDNA mutations are common in patients with ovarian carcinoma. The presence of ctDNA mutations after surgery was an independent predictor of less favorable PFS and OS., Competing Interests: Conflicts of interest Shu-Jen Chen, Hua-Chien Chen, Wen Hsiao, and Kien-Thiam Tan are employees of ACT Genomics, Co. Ltd., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: To investigate outcomes and morbidity of patients undergoing secondary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent ovarian cancer., Materials and Methods: Between April 2014 and January 2019, a total of 51 recurrent ovarian cancer patients receiving secondary CRS and HIPEC were retrospectively reviewed., Results: Among the 51 patients, median peritoneal cancer index score was 13 (range 3-34), and completeness of cytoreduction (CC) score of 0/1 was achieved in 41 patients (78.8%). Regimen of HIPEC included cisplatin and paclitaxel in 39 (75%) cases. The median follow-up duration of survivors was 20.2 months. Sixteen (30.8%) patients remained free of recurrence after HIPEC. The median progression-free survival (PFS) and overall survival (OS) were 11.8 months and 34.5 months respectively. Multivariate analysis showed previous chemotherapy <2 lines (HR 0.24, 0.11-0.52; p = 0.001), chemotherapy-free interval ≥6 months (HR 0.19, 0.09-0.37; p < 0.001) and CA125 < 35 U/mL before HIPEC (HR 0.133, 0.021-0.0832; p = 0.031) were good prognostic factors for PFS. CC0/1 was not significant in multivariate analysis. The most common grade 3/4 toxicity was anemia (17.3%), pleural effusion (11.5%) and renal insufficiency (5.7%). Patients with age ≥50, peritoneal carcinomatosis index (PCI) ≥ 11, operation time ≥10 h and diaphragm surgery had significantly higher incidence of pleural effusion., Conclusions: The current study showed adding HIPEC to secondary CRS might prolong PFS especially in patients with previous chemotherapy <2 lines, chemotherapy-free interval ≥6 months and CA125 < 35 U/mL before HIPEC., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Objective: The objective of this study is to evaluate the safety and efficacy of adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after neoadjuvant chemotherapy (NAC) and interval debulking surgery (IDS) for stage III/IV ovarian, tubal, and primary peritoneal cancer., Study Design: This phase II clinical trial using Simon's minimax two-stage design was conducted. At the first stage, 13 subjects were enrolled, and the trial would proceed to second stage if ≤3 subjects discontinued treatment for study-defined significant adverse events (AEs). Patients with stage III/IV ovarian, tubal, and primary peritoneal cancer deemed not feasible for primary cytoreductive surgery were enrolled after 3-4 cycles of NAC and IDS without disease progression. NAC could be either weekly paclitaxel (80 mg/m 2 ) (dose-dense) plus 3-weekly carboplatin (AUC5-6) or 3-weekly conventional schedule. After IDS, postoperative dose-dense adjuvant chemotherapy for 3 cycles at least (best to 6 cycles), and 3-weekly bevacizumab 15 mg/kg was given since postoperative cycle 2. Further 3-weekly maintenance bevacizumab 15 mg/kg was given intravenously for 17 cycles., Results: Of the 22 enrolled subjects, 13 (59.1 %) had no gross lesion after IDS. Of the 13 subjects enrolled on the 1 st stage, one study-defined significant AE occurred, therefore the trial proceeded to the 2nd stage (n = 9). The median progression-free survival (PFS) was 22.1 months (95 % confidence interval [CI], 13.7-30.5), and the median overall survival (OS) was 49.2 months (95 % CI, 33.8-64.6). Peritoneal Cancer Index score at entering abdomen during IDS was significant for PFS (>12 vs ≤ 12: p = 0.003). One of the 22 subjects did not receive any study treatment. In the safety analysis (n = 21), grade 3/4 AEs included thrombocytopenia of 38.1 %, neutropenia 71.4 %, and anemia 28.6 %. Study-defined significant AEs of bowel perforation, poor-healing wound, and hypertension were found in 1 case each, respectively., Conclusion: This phase II trial demonstrated adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after NAC was feasible with tolerable toxicity and comparable PFS/OS as compared to other studies using bevacizumab in the NAC phase or dose-dense scheduling throughout., Competing Interests: Declaration of Competing Interest Lai CH, Lin H and Qiu JT report free bevacizumab supply from Roche for this trial. Lai CH reports honorarium from ACT Genomics., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The molecular underpinnings of seromucinous borderline tumor (SMBT) - an uncommon ovarian epithelial neoplasm characterized by association with endometriosis, frequent bilateral ovarian involvement, and occasional progression to invasive carcinoma - remain poorly understood. Here, we sought to comprehensively characterize the mutational landscape of SMBT and elucidate the clonal relationship between bilateral ovarian SMBTs. We also compared the mutational profiles between SMBTs and concurrent invasive carcinomas. Formalin-fixed, paraffin-embedded tissue specimens were retrieved from 28 patients diagnosed with SMBT. Massively parallel sequencing of 409 cancer-related genes was conducted to identify somatic mutations in 33 SMBT samples and four concurrent invasive carcinoma specimens. TERT promoter mutations were assessed by Sanger sequencing, whereas immunohistochemistry was used as a surrogate tool for detecting deletions or epigenetic silencing of relevant tumor suppressor genes. Twenty-six (92.9%) of the 28 patients were diagnosed with stage I SMBTs. Seven (25%) cases showed bilateral ovarian involvement and 13 (46%) had concomitant endometriosis. Concurrent ovarian carcinomas were identified in three patients, whereas one case had a synchronous endometrial carcinoma. Somatic mutations in the KRAS, PIK3CA, and ARID1A genes were identified in 100, 60.7, and 14.3% of SMBT samples, respectively. In contrast, TERT promoter mutations and DNA mismatch repair deficiencies were absent. Sequencing of paired specimens from patients with bilateral SMBT revealed the presence of at least two shared somatic mutations, suggestive of a clonal relationship. Similarly, we identified shared somatic mutations between SMBT samples and concurrent ovarian carcinoma specimens. Taken together, these findings demonstrated a distinct mutational landscape of SMBT in which (1) KRAS is invariably mutated, (2) PIK3CA is frequently mutated, and (3) TERT promoter mutations and DNA mismatch repair deficiencies are absent. Our findings represent the first extensive characterization of this rare ovarian neoplasm, with potential implications for disease classification and molecular diagnostics.

Objective: The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of BRCA1/2 mutations remain poorly understood. We investigated these issues through a review of hospital records and nationwide Taiwanese registry data, followed by BRCA1/2 mutation analysis in hospital-based cases., Methods: We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify BRCA1/2 mutations and large genomic rearrangements, respectively. When BRCA1/2 mutations were identified in index cases, pedigrees were reconstructed and genetic testing was offered to family members., Results: A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent BRCA1/2 sequencing and germline pathogenic mutations were detected in 7 patients (38.9%, 5 in BRCA1 and 2 in BRCA2 ). All BRCA1/2 mutation carriers had ovarian high-grade serous carcinomas. Of the 12 patients who were alive at the time of analysis, 5 were BRCA1/2 mutation carriers. All of them had family members with BRCA1/2 -associated malignancies., Conclusions: Our results provide pilot evidence that BRCA1/2 mutations are common in Taiwanese patients with metachronous breast and ovarian malignancies, supporting the clinical utility of genetic counseling., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer., Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m², n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA /homologous recombination deficiency (HRD) genes, because BRCA /HRD mutations ( BRCA /HRD m ) are known to be associated with better prognosis., Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19-0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA /HRD m was not significantly biased between the two arms. Wild-type BRCA /non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11-1.18; p=0.091)., Conclusions: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Objective: To assess the feasibility and survival outcomes of laparoscopic staging for patients with stage I ovarian cancer., Materials and Methods: Consecutive patients who underwent laparoscopic staging surgery for stage I ovarian cancer from January 2002 to December 2014 were evaluated retrospectively by chart review., Results: Twenty-four patients with mean age 43.9 ± 9.9 years and mean body mass index 24.0 ± 3.8 kg/m 2 were included, in which 12 (50%) patients were in stage IA and 12 (50%) in stage IC. The histological types included serous in 6 (25%), mucinous in 7 (29.1%), endometrioid in 6 (25%), clear cell in 5 (20.8%) patients. The mean surgical time was 306.4 ± 98.5 min, and the mean blood loss was 204.2 ± 188.6 mL. None of the patients required conversion to laparotomy. The median numbers of resected pelvic and para-aortic lymph nodes were 20 and 4, respectively. One (4.1%) patient encountered bowel injury intraoperatively, and the other 1 (4.1%) patient hydronephrosis postoperatively. The overall survival rate was 95% in the current series in a median follow-up of 31.5 months., Conclusion: Laparoscopic staging surgery performed for early stage ovarian cancer has better long term survival outcomes than the literature report. Laparoscopic treatment by a trained gynecologic oncologist is an ideal alternative for early stage ovarian cancer with the advantage of minimal invasiveness., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: Bevacizumab (BEV) has been used for ovarian cancer (OC) for years in Taiwan, but the associated data related to outcome is scant. This retrospective study reviewed patients with OC treated with BEV and analyzed their results., Patients and Methods: All patients with OC treated with BEV from 2009 to 2015 in the Linkou branch of Chang Gung Memorial Hospital in Northern Taiwan were included. According to the means of administration, the patients were classified into 6 groups as follows: A-BEV plus chemotherapy (C/T) for initial platinum-resistant (PR) recurrent OC, B-BEV plus C/T for initial platinum-sensitive (PS) recurrent OC, C-BEV alone for recurrent OC, D-BEV plus 1st adjuvant C/T, E-BEV plus neoadjuvant C/T, and F-intraperitoneal (IP) BEV. Progression-free survival (PFS), overall survival (OS), hazard ratios (HRs), overall response rate (ORR), and mean number of BEV cycles were analyzed for groups A to E. Clinical improvement of ascites was assessed for group F., Results: A comparison of early use (only one round of prior C/T) versus late use (multiple rounds of prior C/T) in patients of groups A and B showed a superior PFS (8.27 vs. 3.67, p = 0.037) in the early use group. No significant differences were found between groups A and B (PFS: 4.24 vs. 4.17 months, p = 0.690; OS: 10.06 vs. 9.93 months, p = 0.819; mean BEV cycles: 4.63 vs. 5.0 p = 0.992; ORR: 48.1% vs. 53.5%, p = 0.425). Comparing the response and non-response subgroups of patients in groups A and B, a better outcome was associated with endometrioid type cell (HR = 0.28, p = 0.008), good ECOG performance status (HR = 0.51, p = 0.005), and lack of ascites (HR = 0.67, p = 0.004). Comparing group C with groups A plus B, the BEV alone group had a poorer PFS (1.02 VS. 4.19, p = 0.04) and OS (1.42 VS. 9.99 p = 0.001) than the BEV plus C/T group. In group F, a good clinical benefit rate (85.6%) of ascites improvement was noted. Two patients had grade 5 gastrointestinal bleeding and venous/arterial thromboembolic events after administration of BEV. Grade 3 neutropenia and thrombocytopenia occurred more frequently in our study., Conclusion: Early use of BEV combined with chemotherapy had a significant benefit in PFS for patients with recurrent OC. BEV plus chemotherapy was better than BEV alone for recurrent OC. In addition, IP BEV was helpful for improving clinical ascites.

Objective: To evaluate the incidence and prognosis of unexpected epithelial ovarian cancers (EOCs) occurring in presumed benign endometrioma., Materials and Methods: Patients who underwent primary surgery at Chang Gung Memorial Hospital between November 2003 and October 2013 were searched with the Systematized Nomenclature of Medicine code followed by chart review., Results: The incidence of unexpected EOCs in presumed ovarian endometrioma was 0.14%, as 11 patients were revealed after reviewing 497 patients of pathology-proven EOCs in the current series. All patients were aged ≥ 40 years; seven (63.6%) had inward mass within ovarian cyst in preoperative images, six had cancer antigen-125 (CA-125) > 200 U/mL, and two with CA-125 > 1500 U/mL. Ten patients underwent laparoscopy initially, including five with ovarian preservation at the beginning. Ten patients subsequently completed concurrent or secondary staging surgery, including four totally with laparoscopy. The histologic subtypes had clear-cell (8/11), endometrioid (1/11), mixed clear-cell and endometrioid (1/11), and low-grade serous adenocarcinoma (1/11). Seven patients had endometriosis-associated ovarian carcinoma (EAOC), while the other four were non-EAOC with no endometriosis component. The only mortality was a patient of non-EAOC in Stage IIIc, whereas the other 10 in Stage I were alive. The overall survival rate was 90.9% (10/11) with follow-up ranging from 23 months to 130 months., Conclusion: Unexpected EOCs occurring in presumed ovarian endometrioma was rare and, if present, the prognosis was good in Stage I disease with laparoscopic management. Combining parameters of patient's age, CA-125 level, and inward solid mass at imaging could help to raise the precautions., (Copyright © 2017 Taiwan Association of Obstetrics & Gynecology. Published by Elsevier B.V. All rights reserved.)

Objectives: Synchronous endometrial and ovarian carcinomas (SEOCs) present gynecologic oncologists with a challenging diagnostic puzzle: discriminating between double primary cancers and single primary cancer with metastasis. We aimed to determine the clonal relationship between simultaneously diagnosed endometrial and ovarian carcinomas., Methods: Fourteen pairs of SEOCs of endometrioid type and two pairs of SEOCs with disparate histologic types (control for dual primary tumors) were subjected to massively parallel sequencing (MPS) and molecular inversion probe microarrays., Results: Thirteen of the 14 pairs of SEOCs harbored somatic mutations shared by both uterine and ovarian lesions, indicative of clonality. High degree of chromosomal instability in the tumors from 10 patients who received adjuvant chemotherapy, of whom 9 had synchronous carcinomas with significantly overlapping copy number alterations (CNAs), suggestive of single primary tumors with metastasis. The clonal relationship determined by genomic analyses did not agree with clinicopathological criteria in 11 of 14 cases. Minimal CNAs were identified in both ovarian and endometrial carcinomas in 4 patients, who did not receive adjuvant chemotherapy and experienced no recurrent diseases. In contrast, two of the 10 patients with chromosomally unstable cancers developed recurrent tumors., Conclusion: Our findings support a recent paradigm-shifting concept that most SEOCs originate from a single tumor. It also casts doubt on the clinicopathological criteria used to distinguish between dual primary tumors and single primary tumor with metastasis. Testing of CNAs on SEOCs may help determining the need of adjuvant therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To identify candidate microRNAs (miRNAs) in the serum of patients with clear cell carcinomas in monitoring disease progression., Materials and Methods: The sera of patients with diagnosed ovarian clear cell carcinoma were collected from 2009 to 2012. Real-time quantitative polymerase chain reaction (PCR) analysis for 270 miRNAs was performed. To offset the potential extraction bias, an equal amount of Caenorhabditis elegans cel-miR-238 was added to each serum specimen before miRNA isolation. miRNA expression was analyzed using the ΔCt method, with cel-miR-238 as controls., Results: Twenty-one patients with clear cell carcinoma were included. In the discovery phase on four pairs of pre- and postoperative sera, 18 differentially expressed miRNAs were selected from 270 miRNAs. In the validation phase on an independent set of 11 pairs of pre- and postoperative sera, 4 miRNAs (hsa-miR-130a, hsa-miR-138, hsa-miR-187, and hsa-miR-202) were confirmed to be higher in the preoperative sera. In the application phase, hsa-miR-130a remained consistent with the different time points in seven of the 10 patients during clinical follow-up periods. More importantly, in three patients, hsa-miR-130a levels were elevated in early disease recurrences before CA125 was found to be elevated., Conclusion: Hsa-miR-130a may be a useful serum biomarker for detecting recurrence of ovarian clear cell cancer, and warrants further studies., (Copyright © 2014. Published by Elsevier B.V.)

A 21-year-old lady diagnosed with Stage 3 ovarian yolk sac tumor (YST) underwent primary cytoreductive fertility sparing surgery, followed by conventional courses of platinum-based chemotherapy and etoposide. Recurrence at cul-da-sac was noted after a short period of remission and secondary debulking performed followed by four cycles of conventional chemotherapy. The patient's disease progressed despite courses of treatments. A joint team management including a hematologist was commenced following the failure of conventional chemotherapies. Two cycles of high-dose chemotherapy (HDCT) with ifosfamide/cisplatin/etoposide (ICE) regimen, followed by autologous stem cell transplantation (ASCT) were given. With this salvage treatment, she remained in complete remission and disease-free for more than 30 months, while maintaining her reproductive function. These approaches appear to be effective as a salvage treatment in selected cases of patients with ovarian germ cell tumor, especially those who failed primary conventional chemotherapy.

Background: The aim of this study was to evaluate the impact on survival of initial laparoscopic surgery compared with conventional laparotomy in stage I epithelial ovarian cancer., Methods: We conducted a retrospective study which enrolled all consecutive patients with stage I epithelial ovarian cancer between January 1984 and December 2006. Patients with a histological diagnosis of epithelial ovarian cancer who underwent laparoscopy were recruited if their cases were compatible with stage I (clinical or surgical) at initial exploration. The independent samples t test, chi-square test, log-rank and Cox proportional hazards model were performed., Results: A total of 208 patients were enrolled, including 34 patients with initial laparoscopy and 174 with laparotomy. The median follow-up time for survivors was 65 (range, 2-276) months. The 5-year overall survival (OS) and recurrence-free survival (RFS) rates were 67.4% and 69.5% in the laparoscopy group, and 88.7% and 78.7% in the laparotomy group, respectively. The median time to recurrence was 14.5 (range, 2-67) months. In multivariate analysis, the initial laparoscopy approach posted significant adverse impacts on the OS (laparoscopy vs laparotomy, the hazard ratio [HR]: 3.52, p=0.009) and the RFS (laparoscopy vs laparotomy, HR: 2.58, p=0.024), while a higher substage (stage IB-IC vs IA, HR: 8.29, p=0.040) was associated with only a worse OS, and its impact on the RFS was marginal., Conclusion: An initial laparoscopy intervention and higher substage posted significant adverse effects on the prognosis in stage I epithelial ovarian cancer. Important precautions when using laparoscopy for adnexal masses, such as avoiding rupture, applying protection, and submitting frozen sections, are recommended.

Objective: We aimed to investigate outcome of borderline ovarian tumors (BOTs) with respect to methods and extent of surgical approach and to evaluate prognostic factors., Methods: A retrospective study included consecutive patients with BOT treated from 1984 to 2008. These cases were confirmed by histological review. The influence of clinico-pathological characteristics upon recurrence and death were analyzed by independent sample t test, Chi-square test, logistic regression model, and Cox proportional hazard model., Results: A total of 233 patients were enrolled, 214 in Stage I, 11 Stage II and 8 Stage III. There were 21 relapses, only 5 of which died of disease. 5-year and 10-year overall survival were 97.6% and 96.4%, and recurrence-free survival rates (RFS) were 92.7% and 88.2%, respectively. Median follow-up time for survivors was 81 (range, 0.5-295) months. Median time to recurrence was 31 (range, 5.5-181) months. In multivariate analysis, Stage II/III, cystectomy and higher pretreatment serum CA-125 level (>or=144 U/mL) were selected for a model predicting 5-year RFS, where risk factor=0, 1, and 2-3 had odds ratios of 1, 14.9, and 113.3, respectively (p<0.001). Replacing stage with peritoneal implants, the latter two factors along with invasive peritoneal implants were selected. Of the 5 cases died of disease, all had invasive recurrences. Initial laparoscopic or laparotomy approach had no influence on prognosis., Conclusions: Although BOT has an excellent prognosis, they are not exempted from a risk of recurrence. Stage II/III (or invasive implants), cystectomy and higher pre-operative serum CA-125 were independent variables predicting recurrence.

Great advances in technology offer meticulous options of minimally invasive surgery to empower the gynecologists to manage patients of early ovarian cancer. Laparoscopy affords improved visualization of the pelvic peritoneum, diaphragm and the deep pelvic structures, and offers many advantages in the avoidance of long abdominal incision, including shorter hospital stay and a more rapid recovery time. Most studies showed that laparoscopy did not compromise the survival and recurrence prognosis in comparison with open abdominal approach of staging surgery. Contrarily, laparoscopy precludes the advantage of open surgery, such as manual examination of the full extent of the bowel and palpation of lymph nodes. Besides, laparoscopy technically hampers the removal of large ovarian mass, and laparoscopic cancer surgery has a potential risk of trocar site metastasis. As the trend shows that laparoscopy has been playing an important role in treating early ovarian cancer, we could expect laparoscopy to become an attractive surgical option in the future for ovarian cancers.

Objective: The purpose of this study was to define the clinical features and long-term prognosis of port-site metastasis after primary laparoscopic surgery for ovarian cancer., Study Design: All the patients with epithelial ovarian cancer or borderline malignancy who had undergone primary laparoscopic surgery at our institution were reviewed. The clinicopathologic parameters, flow cytometric parameters, p53, p27, bax, HER-2/neu, and bcl-2 by immunostaining, presentation of port-site implants, management of the individual patient, and long-term outcome were analyzed. CANCERLINE and MEDLINE (1960-2002) were searched for related papers., Results: Between 1993 and 2001, of the 31 patients with epithelial ovarian cancer or borderline malignancy who underwent primary laparoscopic surgery at Chang Gung Memorial Hospital, 6 (19.4%) had port-site metastasis. The other 2 patients were referred after port-site metastasis. Tumors with port-site recurrences had higher S-fraction than those without (median: 18.2% vs 9.9%, P =.003; relative risk ratio: >15.5% vs

Treatment results of 26 patients with squamous cell carcinoma (SCC) arising in mature cystic teratoma of the ovary were analyzed. Four nulliparous patients with stage Ia tumors underwent conservative salpingo-oophorectomy. Following surgery, 2 patients had successful pregnancies. The remaining 7 patients with stage Ia tumors were observed after hysterectomy and bilateral salpingo-oophorectomy. Fifteen patients with stage Ic-IV tumors underwent cytoreductive surgery followed by cis-platinum-based chemotherapy with or without sequential radiotherapy. The mean survival was 63.9 months. The overall actuarial disease-free survival at 2 years was 69%, and by stage was as follows: stage I, 100% (13/13); stage II, 100% (2/2); stage III, 30% (3/10); and stage IV, 0% (0/1). A significant difference in disease-free survival was noted in stage (P = 0.0001). Optimal versus suboptimal operation was associated with a median Kaplan-Meier survival of 65 months versus 34.8 months, with actuarial disease-free survival at 2 years of 60 and 0%, respectively (P = 0.0210). Our study shows that 67% (16/24) of the patients had SCC antigen levels exceeding 2 ng/ml, which by stage was as follows: stage I, 5/11 (45%); stage II, 1/2 (50%); stage III, 9/10 (90%); and stage IV, 1/1(100%). After completion of treatment, all 8 patients with recurrent lesions had reelevated SCC antigen levels in series SCC antigen monitoring. In conclusion, positive prognostic factors of disease-free survival were optimal cytoreduction and lower FIGO stage. We suggest that multimodality therapy, including aggressive cytoreduction followed by cis-platinum-based chemotherapy with or without sequential radiotherapy, is recommended. In addition, we suggest that serum SCC antigen monitoring may be helpful in early detection of cancer recurrence.

Background: The role of flow cytometric DNA analysis in predicting prognosis of patients with borderline malignant ovarian tumors has been controversial., Methods: Fifty cases of patients with borderline malignant ovarian tumors were analyzed by histology and by flow cytometry on paraffin embedded tissue. Multiple tissue blocks and serial sections were analyzed for each tumor. The results of DNA analysis were correlated to clinicopathologic data., Results: DNA aneuploidy was demonstrable in 4 cases (8%) when the most atypical section was analyzed. The overall rate of aneuploidy was 14% if additional blocks and serial sections were studied. Two patients died from tumor. One of the two patients had an initial diagnosis of Stage IIc mucinous borderline tumor with DNA indices (DI) of 1.12, 1.42, and 2.04. She had a recurrence in the contralateral ovary 1 year later (DI = 1.83), and a second frankly malignant recurrence diffusely in peritoneum (DI = 1.89). The other patient had an initial diagnosis of Stage IIIc mucinous borderline ovarian tumor with pseudomyxoma peritonei. DNA diploidy was obtained in all of the samples from the primary tumor. An aneuploid peak (DI = 1.28) was demonstrated in only one serial section of the peritoneal implants. Of the other 5 patients who had aneuploid histograms but were disease-free, the DNA indices were 1.35, 1.14/1.18, 1.15, 1.20, and 1.31 and were demonstrable only in either 1 or 2 of the blocks or unproven on serial sections. All patients with diploid-peridiploid tumors were alive and disease free., Conclusions: Reproducible DNA aneuploidy of high DI may be predicting a poor outcome, whereas the significance of inconsistently reproducible aneuploidy of low DI remains to be determined. Further studies of prospective DNA analysis with adequate sampling are necessary to define the role of flow cytometry in patients with borderline malignant ovarian tumors.