The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells.

The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured when informed by the molecular signatures of the normal fallopian tube epithelium (FTE) cells, the cells of origin of SOC. Surveying the transcriptomes of ∼6,000 FTE cells, predominantly from non-ovarian cancer patients, identified 6 FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH. Importantly, NGH-based stratification of ∼1,700 tumors robustly correlated with survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC.

Morbidity of multiple bowel resection compared to single bowel resection after debulking surgery for ovarian cancer.

OBJECTIVES: To assess the impact of multiple bowel resections on postoperative outcomes in stage IIIC-IV ovarian cancer (OC). METHODS: From the Oxford OC database we retrieved consecutive patients who underwent bowel resection between January 2009 and November 2017. Patients were divided into two groups: single bowel resection (SBR) and MBR (≥2 bowel resections). The following outcomes were compared between the two groups: 30-day related and not related morbidity to bowel surgery, bowel diversion rate and time to start/restart adjuvant chemotherapy. RESULTS: Thirty-five patients were in the MBR and 146 in the SBR group. The 30-day overall surgical-related complication and bowel specific complications rate was higher in MBR group than SBR group (54.3% vs. 23.9%, p < 0.001) and (25.7% vs. 10.5%, p = 0.035), respectively. The rate of bowel diversion was 97.7% in MBR vs. 26.7% in the SBR group (p = 0.021). Trend analysis showed a significant reduction in the rate of MBR after the introduction of NACT (p- for trend <0.001). CONCLUSIONS: Our data show that MBR during OC surgery is associated with a higher rate of overall and bowel specific complication compared to SBR. The introduction of NACT is associated with a reduced rate of MBR.

Concomitant Laparoscopic and Thoracoscopic Resection of Recurrent High-Grade Ovarian Cancer.

STUDY OBJECTIVE: To describe the first case of combined endoscopic management of a thoracic and abdominal recurrence of ovarian cancer. DESIGN: An instructive video showing the combined thoracic and abdominal surgical procedure. SETTING: Department of Gynecological Oncology, Churchill Hospital, Oxford University, UK. PATIENTS: A 64-year-old woman undergoing endoscopic treatment for a third recurrence of ovarian cancer after a full surgical staging in 2007. The disease-free interval from the last recurrence was 31 months. INTERVENTION: The operation was performed by a multidisciplinary team of thoracic and gynecologic oncologist surgeons. Surgery started with thoracoscopic resection of a right enlarged paracardiac lymph node of 24 mm and a small wedge of the right lung, which was attached to the lymph node. At laparoscopy, 2 nodules of 3 and 5 mm were excised from the mesosigmoid and 1 nodule of 20 mm was resected from the right hemidiaphragm. MEASUREMENTS AND MAIN RESULTS: The total operative time was 251 minutes, and no intraoperative complication occurred. No conversion to open surgery was necessary. The estimated blood loss was 50 mL. There was no visible residual disease at the end of the surgery. The patient was discharged 4 days after surgery. The final pathology report confirmed the presence of endometrioid adenocarcinoma in all specimens removed. Adjuvant chemotherapy with carboplatin/paclitaxel was started 2 weeks later. At the 60-day follow-up, no complications were recorded. A computed tomographic scan performed after 6 cycles of chemotherapy did not reveal any evidence of relapse. CONCLUSIONS: The combined endoscopic approach might be feasible in selected patients.

Morbidity and reversal rate of ileostomy after bowel resection during Visceral-Peritoneal Debulking (VPD) in patients with stage IIIC-IV ovarian cancer.

OBJECTIVE: To investigate the morbidity of diverting loop ileostomy (DLI) performed during Visceral Peritoneal Debulking (VPD) for stage IIIC-IV ovarian cancer and to report the rate, timing, and morbidity of DLI reversal. METHODS: We retrieved the data of all consecutive patients who underwent sigmoid-rectum resection (SRR) followed by DLI. Morbidity was defined as any surgical/medical complications clearly correlated to the DLI. The reversal rate of DLI was defined as the number of patients who had the continuity of the gastrointestinal tract restored in the study period. Finally, we recorded the timing and the morbidity of the reversal surgery. Factors associated with non-reversal of DLI were reported. RESULTS: In the study period (01/2010-09/2016), complete data were available for 47 patients. Stoma-related complications occurred in 22 patients (46.8%). Eight patients (17.0%) were readmitted within 30days from surgery. Thirty-two patients (68.1%) had their stoma reversed. The primary cause of non-reversal was tumor recurrence/progression (7/15, 46.7%). Patient's age, length of hospitalization, complications after VPD were associated with non-reversal of DLI. The mean time from DLI formation to stoma reversal was 6months (±1.7). Post-reversal related complications occurred in 37.1% of the patients. CONCLUSIONS: In our series, 31.9% of the patients with FIGO stage IIIC-IV ovarian cancer who underwent SRR and DLI did not have stoma reversal. Overall they had approximately 45% risk of stoma-related morbidity and 37% risk of morbidity related to the stoma reversal. This information should be part of the consulting process when preparing for debulking surgery, particularly in patients who are likely to need a bowel resection.

En-bloc resection of the pelvis (EnBRP) in patients with stage IIIC-IV ovarian cancer: A 10 steps standardised technique. Surgical and survival outcomes of primary vs. interval surgery.

OBJECTIVE: In this study we describe the technique of the En-bloc resection of the pelvis (EnBRP) in 10 standardised and reproducible steps, whereby all pelvic organs, except the bladder, are removed together with the peritoneum. In addition, we compare the surgical and survival outcomes of patients who underwent upfront vs. interval surgery. METHODS: Retrospective analysis of patients with FIGO Stage IIIC-IV ovarian cancer treated with Visceral Peritoneal Debulking (VPD) who had EnBRP. The study population was divided into Group 1 (up-front VPD) and group 2 (VPD after neo-adjuvant chemotherapy). The aim was to assess the incidence of EnBRP. We also assessed rate of complete resection (CR), procedure-specific and overall morbidity, disease free and overall survival. Results were compared between group 1 and 2. RESULTS: Overall 92 out of 200 patients (46%) needed an EnBRP during the VPD. Forty-eight patients were in Group 1 and 44 patients in Group 2. CR was achieved in all patients. No intra-operative procedure specific morbidity was recorded. Dehiscence of bowel anastomosis was the only procedure specific morbidity. Rate was 2%, with 1 episode recorded in each group. Both patients were managed and settled with formation of a bowel diversion. The overall morbidity rate was 33%, 35% in group 1 and 31% in group 2. The mortality rate was 1%. Median disease free survival was 20months, 25 in group 1 vs. 15 in group 2 (P=0.009). CONCLUSIONS: EnBRP is a safe and effective technique to tackle the pelvic disease of patients with advanced ovarian cancer. The reduced blood loss, the high rate of clear margins and CR of the disease are accompanied by a low rate of surgical morbidity. These features are particularly suitable for patients who are due to start or re-start chemotherapy. The standardization of the technique will make it more reproducible and easier to be taught. In addition, it will facilitate comparison of results and the inclusion of this technique in the portfolio of procedures as part of debulking surgery.

Porta hepatis peritonectomy and hepato-celiac lymphadenectomy in patients with stage IIIC-IV ovarian cancer: Diagnostic pathway, surgical technique and outcomes.

OBJECTIVE: To report the surgical technique of ovarian cancer resection at the porta hepatis (PH) and hepato-celiac lymph nodes (HCL). To assess surgical and survival outcomes. Define the accuracy of an integrated diagnostic pathway. METHODS: Patients with FIGO stage IIIC-IV ovarian cancer that underwent Visceral-Peritoneal Debulking (VPD). Data of patients with disease at the PH/HCL during VPD were extracted from our database. The CT scan findings were compared with the exploratory laparoscopy. Accuracy of CT scan, intra- and post-operative morbidity, rate of complete resection (CR), disease free and overall survival are reported. RESULTS: Thirty one patients out of 216 (14.3%) had tumor at the PH and/or HCL. In 8 patients out of 31 (25.8%) it was only found with the aid of the exploratory laparoscopy. CR was achieved in 28 patients out of 31 (90.3%). Pathology confirmed disease in the PH/HCL specimens of all but one patient. Overall morbidity relating to the VPD was 29.2%. No complication was specifically related to the PH/HCL. Median disease free survival was 19months and median overall survival was 42months. CONCLUSION: PH/HCL surgery was required in 15% of patients with FIGO stage IIIC-IV. The surgery was feasible, safe and significantly contributed to CR. CT scan failed to identify the disease in 31% of the patients. CT and laparoscopy correctly identified all patients.