Recurrent High-grade Serous Cancer Research Articles

Laparoscopic Resection of a High Grade Serous Ovarian Cancer that Recurred at the Vaginal Stump with Extensive Pelvic Adhesions after Complete Surgical Staging

To show laparoscopic resection of a high grade serous ovarian cancer that recurred at the vaginal stump with extensive pelvic adhesions after complete surgical staging. Stepwise demonstration of the procedure with narrated video footage. University hospital. We reported a case of a 62-year-old woman with a history of complete surgical staging of high grade serous ovarian cancer staged IIB, which consisted of hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node dissection, and omentectomy, about 18 months before this admission. She received 6 courses of carboplatin/paclitaxel combination therapy after complete surgical staging and achieved complete remission. About 12 months after the last course of chemotherapy, she visited the local clinic because of irregular vaginal bleeding. Physical examination revealed a 3×3×2 cm3 mass at the vaginal vault. Biopsy of the mass was performed under colposcopy, and pathological reports showed recurrent high grade serous cancer. Her serum cancer antigen 125 level was in normal range. Positron emission tomographic/computed tomographic imaging (PET/CT) showed no evidence of disease dissemination. A diagnosis of recurrent high grade serous ovarian cancer was made. After the biopsy of the recurrent mass, there were no visible lesions, which made us believe that laparoscopy management would not contribute to intraperitoneal spread of the tumors. Therefore, laparoscopic resection of the vaginal stump was scheduled. The key steps of the procedure were summarized as follows. First, the bowels were released from the side abdominal wall to expose bilateral external iliac vessels. Second, bilateral ureters were identified and mobilized to avoid incidental ureter injuries. Third, we opened the rectovaginal space and detached the rectum from the posterior vaginal wall. Fourth, the posterior vesical wall was separated from the vaginal stump. After exposure of the key anatomic landmarks, laparoscopic resection of the vaginal stump was performed safely. Final pathologic report showed recurrent high grade serous ovarian cancer. The patient received 6 courses of carboplatin/paclitaxel combination therapy, and maintenance therapy with olaparib was suggested, but the patient refused to accept this suggestion. She is still in complete remission 8 months after surgery. Laparoscopic resection of a high grade serous ovarian cancer that recurred at the vaginal stump with extensive pelvic adhesions after complete surgical staging was achieved successfully in a logical way. The critical point of the procedure is to expose the key anatomic landmarks of the pelvis to avoid incidental injuries [1].

Single-agent bevacizumab for the management of refractory malignant effusions in heavily pretreated patients with recurrent high-grade serous cancers of the ovary, fallopian tube or peritoneum: results from a single institution

Single-agent bevacizumab for the management of refractory malignant effusions in heavily pretreated patients with recurrent high-grade serous cancers of the ovary, fallopian tube or peritoneum: results from a single institution

Strong synergy with APR-246 and DNA-damaging drugs in primary cancer cells from patients with TP53 mutant High-Grade Serous ovarian cancer

BackgroundMutation in the tumor suppressor gene TP53 is an early event in the development of high-grade serous (HGS) ovarian cancer and is identified in more than 96 % of HGS cancer patients. APR-246 (PRIMA-1MET) is the first clinical-stage compound that reactivates mutant p53 protein by refolding it to wild type conformation, thus inducing apoptosis. APR-246 has been tested as monotherapy in a Phase I/IIa clinical study in hematological malignancies and prostate cancer with promising results, and a Phase Ib/II study in combination with platinum-based therapy in ovarian cancer is ongoing. In the present study, we investigated the anticancer effects of APR-246 in combination with conventional chemotherapy in primary cancer cells isolated from ascitic fluid from 10 ovarian, fallopian tube, or peritoneal cancer patients, 8 of which had HGS cancer.MethodsCell viability was assessed with fluorometric microculture cytotoxicity assay (FMCA) and Combination Index was calculated using the Additive model. p53 status was determined by Sanger sequencing and single strand conformation analysis, and p53 protein expression by western blotting.ResultsWe observed strong synergy with APR-246 and cisplatin in all tumor samples carrying a TP53 missense mutation, while synergistic or additive effects were found in cells with wild type or TP53 nonsense mutations. Strong synergy was also observed with carboplatin or doxorubicin. Moreover, APR-246 sensitized TP53 mutant primary ovarian cancer cells, isolated from a clinically platinum-resistant patient, to cisplatin; the IC50 value of cisplatin decreased 3.6 fold from 6.5 to 1.8 μM in the presence of clinically relevant concentration of APR-246.ConclusionThese results suggest that combination treatment with APR-246 and DNA-damaging drugs could significantly improve the treatment of patients with TP53 mutant HGS cancer, and thus provide strong support for the ongoing clinical study with APR-246 in combination with carboplatin and pegylated liposomal doxorubicin in patients with recurrent HGS cancer.