Surgery In Ovarian Cancer Patients Research Articles

Optimal debulking surgery in ovarian cancer patients: MRI may predict the necessity of rectosigmoid resection

ObjectivesTo determine whether MRI can predict the necessity of rectosigmoid resection (RR) for optimal debulking surgery (ODS) in ovarian cancer (OC) patients and to compare the predictive accuracy of pre- and post-neoadjuvant chemotherapy (NACT) MRI.MethodsThe MRI of 82 OC were retrospectively analyzed, including six bowel signs (length, transverse axis, thickness, circumference, muscularis involvement, and submucosal edema) and four para-intestinal signs (vaginal, parametrial, ureteral, and sacro-recto-genital septum involvement). The parameters reflecting the degree of muscularis involvement were measured. Patients were divided into non-RR and RR groups based on the operation and postoperative outcomes. The independent predictors of the need for RR were identified by multivariate logistic regression analysis.ResultsImaging for 82 patients was evaluated (67 without and 15 with NACT). Submucosal edema and muscularis involvement (OR 13.33 and 8.40, respectively) were independent predictors of the need for RR, with sensitivities of 83.3% and 94.4% and specificities of 93.9% and 81.6%, respectively. Among the parameters reflecting the degree of muscularis involvement, circumference ≥ 3/12 had the highest prediction accuracy, increasing the specificity from 81.6% for muscularis involvement only to 98.0%, with only a slight decrease in sensitivity (from 94.4% to 88.9%). The predictive sensitivities of pre-NACT and post-NACT MRI were 100.0% and 12.5%, respectively, and the specificities were 85.7% and 100.0%, respectively.ConclusionsMRI analysis of rectosigmoid muscularis involvement and its circumference can help predict the necessity of RR in OC patients, and pre-NACT MRI may be more suitable for evaluation.Critical relevance statementWe analyzed preoperative pelvic MRI in OC patients. Our findings suggest that MRI has predictive potential for identifying patients who require RR to achieve ODS.Key PointsThe need for RR must be determined to optimize treatment for OC patients.Muscularis involvement circumference ≥ 3/12 could help predict RR.Pre-NACT MRI may be superior to post-NACT MRI in predicting RR.Graphical

Surgical evidence-based comparison of [68Ga]Ga-FAPI-04 PET and MRI-DWI for assisting debulking surgery in ovarian cancer patients.

Imaging assessment of abdominopelvic tumor burden is crucial for debulking surgery decision in ovarian cancer patients. This study aims to compare the efficiency of [68Ga]Ga-FAPI-04 FAPI PET and MRI-DWI in the preoperative evaluation and its potential impact to debulking surgery decision. Thirty-six patients with suspected/confirmed ovarian cancer were enrolled and underwent integrated [68Ga]Ga-FAPI-04 PET/MRI. Nineteen patients (15 stage III-IV and 4 I-II stage) who underwent debulking surgery were involved in the diagnostic efficiency analysis. The images of [68Ga]Ga-FAPI-04 PET and MRI-DWI were visually analyzed respectively. Immunohistochemistry on FAP was performed in metastatic lesions to investigate the radiological missing of [68Ga]Ga-FAPI-04 PET as well as its different performance in primary debulking surgery (PDS) and interval debulking surgery (IDS) patients. Potential imaging impact on management was also studied in 35 confirmed ovarian cancer patients. [68Ga]Ga-FAPI-04 PET displayed higher sensitivity (76.8% vs.59.9%), higher accuracy (84.9% vs. 80.7%), and lower missing rate (23.2% vs. 40.1%) than MRI-DWI in detecting abdominopelvic metastasis. The diagnostic superiority of [68Ga]Ga-FAPI-04 PET is more obvious in PDS patients but diminished in IDS patients. [68Ga]Ga-FAPI-04 PET outperformed MRI-DWI in 70.8% abdominopelvic regions (17/24), which contained seven key regions that impact the resectability and surgical complexity. MRI-DWI hold advantage in the peritoneal surface of the bladder and the central tendon of the diaphragm. Of the contradictory judgments between the two modalities (14.9%), [68Ga]Ga-FAPI-04 PET correctly identified more lesions, particularly in PDS patients (73.8%). In addition, FAP expression was independent of lesion size and decreased in IDS patients. [68Ga]Ga-FAPI-04 PET changed 42% of surgical planning that was previously based on MRI-DWI. [68Ga]Ga-FAPI-04 PET is more efficient in assisting debulking surgery in ovarian cancer patients than MRI-DWI. Integrated [68Ga]Ga-FAPI-04 PET/MR imaging is a potential method for planning debulking surgery in ovarian cancer patients.

The impact of splenectomy and diaphragmatic surgery on perioperative morbidity and overall survival of ovarian cancer patients.

The prognosis of ovarian cancer (OC), among other factors, depends on residual disease after primary debulking surgery (PDS) and initial disease advancement. The main aim of our study was to evaluate the survival benefits of splenectomy and diaphragmatic surgery in OC patients, when the procedures result in resection to no macroscopic residual disease or minimal residual disease [tumor nodules below 2.5 mm according to Sugarbaker's completeness of cytoreduction score (CC) = 1]. The study included 25 OC patients after splenectomy procedures, 28 patients after diaphragmatic surgery and 17 patients who had undergone both splenectomy and diaphragmatic surgery. Patients' overall survival (OS) was compared with residual disease-matched controls (47 patients) who had upper abdomen involvement but no requirement for splenectomy and/or diaphragmatic surgery. Overall survival of patients after splenectomy was not significantly different from OS of patients who did not required splenectomy (36.1 vs 31.6 months; p = 0.85). No differences in OS were observed between patients who did and did not require diaphragmatic surgery (31.3 vs 41.8; p = 0.33). Similarly, we found no differences in OS between patients who underwent both splenectomy and diaphragmatic surgery and those patients who did not require either procedure (20.1 vs 31.6 months; p = 0.45). Splenectomies and diaphragmatic surgeries were associated with prolonged hospitalization and length of surgery, however, no specific morbidity related to the procedures was observed. In the cases of advanced OC, diaphragm and spleen involvement do not hamper patient prognosis when adequately resected.

Maximal Effort Cytoreduction in Epithelial Ovarian Cancer: Perioperative Complications and Survival Outcomes from a Retrospective Cohort.

Background: Rates of maximal effort cytoreductive surgery in ovarian cancer patients increase gradually the last decade. The purpose of the present study is to evaluate factors that contribute to survival and morbidity outcomes in this group of patients. Methods: We retrospectively reviewed patient records of epithelial ovarian cancer patients with an intermediate and high Mayo Clinic surgical complexity score, operated between January 2010 and December 2018. Results: Overall, 107 patients were enrolled in the present study with a median age of 62 years (23-84) and a follow-up of 32 months (2-156). Thirteen Clavien-Dindo grade IIIa complications were documented in 10 patients (9.3%). Of all the investigated factors, only stage IVb (p = 0.027) and interval debulking surgery (p = 0.042) affected overall survival rates. Overall survival outcomes of patients operated on a primary setting started to differentiate compared to those that received neo-adjuvant chemotherapy after the 4th postoperative year. Conclusions: Maximal effort cytoreductive procedures should be considered feasible in the modern surgical era, as they are accompanied by acceptable rates of perioperative morbidity. Hence, every effort should be made to perform them in the primary setting, rather than following neoadjuvant chemotherapy as current evidence favor increased survival rates of patients that will likely surpass an interval of observation of more than 4 years.

Postoperative paralytic ileus following debulking surgery in ovarian cancer patients.

AimThis study aims to evaluate the incidence of postoperative ileus (POI) following cytoreductive surgery in epithelial ovarian cancer (EOC) patients and its impact on anastomotic leakage occurrence and postoperative complications.MethodsA total of 357 surgeries were performed on 346 ovarian cancer patients between 1/2010 and 12/2020 at our institution. The postoperative course regarding paralytic ileus, anastomotic leakage, and postoperative complications was analyzed by Fisher's exact test and through ordinal logistic regression.ResultsA total of 233 patients (65.3%) returned to normal gastrointestinal functions within 3 days after surgery. A total of 123 patients (34.5%) developed POI. There were 199 anastomoses in 165 patients and 24 leakages (12.1%). Postoperative antibiotics (p 0.001), stoma creation (p 0.0001), and early start of laxatives (p 0.0048) significantly decreased POI, while anastomoses in general (p 0.0465) and especially low anastomoses (p 0.0143) showed increased POI rates. Intraoperative positive fluid excess >5,000 cc was associated with a higher risk for POI (p 0.0063), anastomotic leakage (p 0.0254), and severe complications (p 0.0012).ConclusionPostoperative antibiotics, an early start with laxatives, and stoma creation were associated with reduced POI rates. Patients with anastomoses showed an increased risk for POI. Severe complications, anastomotic leakages, and POI were more common in the case of intraoperative fluid balance exceeding 5,000 cc.

Predicting value of HE4 and CA125 markers for optimal cytoreductive surgery in ovarian cancer patients.

We conducted a cross-sectional study to evaluate the role of serum levels of CA125 and HE4 in predicting optimal cytoreductive surgery. Eligible women who had been diagnosed with ovarian cancer based on both clinical and imaging criteria were enrolled in this study. Serum levels of CA 125 and HE4 were checked before surgery and all patients underwent complete surgical staging. After completion of the pathological evaluation, data were entered in SPSS version 23. One hundred and ten individuals were enrolled in our study. We divided cases between two groups: stage I to Ш b and stage Шc to IV. Serum level of HE4 >170 pmol/L can predict optimal cytoreductive surgery before operation. (sensitivity:80% and specificity 70%) and serum level of CA 125 > 320 UI/mL can predict optimal cytoreductive surgery before operation. (sensitivity:80% and specificity 70%). Our data demonstrated a negative predictive value of about 80% for both HE4 and CA125. Based on these cut-off, unnecessary surgery can be avoided in many cases, however, it is unwise to ignore clinical performance and radiological findings. Nevertheless, we can say the evaluation of tumor markers is feasible and helpful in predicting optimal surgery.

Germline BRCA mutations are associated with an increased likelihood of secondary cytoreductive surgery in ovarian cancer patients (116)

<b>Objectives:</b> <i>BRCA</i> mutations have been associated with improved outcomes in ovarian cancer patients, specifically with delayed recurrences. This study aimed to compare the secondary cytoreduction rates and eligibility among ovarian cancer patients by <i>BRCA</i> mutation status. <b>Methods:</b> The study was retrospective and included high-grade serous ovarian cancer patients from one Canadian center and two Israeli centers from January 1999 to December 2018, with the first disease recurrence 12 months or more from the last cycle of platinum-based chemotherapy. Demographic and genetic data, tumor characteristics, pattern of recurrence, and surgical and medical treatments were obtained from electronic charts. Eligibility for secondary cytoreduction was defined as recurrence 12 months or longer from completion of adjuvant treatment, up to three lesions at recurrence, and absence of ascites, in line with DESKTOP criteria. Patients were grouped according to <i>BRCA</i> mutation status. Continuous variables were compared using the student's t-test and categorical variables using the Chi-square test. Regression analysis was used to identify predictors of eligibility for and performance of secondary cytoreduction. <b>Results:</b> One hundred forty-seven patients were enrolled, including 97 from Canada and 50 from Israel. Forty-seven patients (32%) had a <b>Conclusions:</b> Germline <i>BRCA</i> mutation carriers are more likely to undergo secondary cytoreduction, most likely due to lower volume disease at recurrence. This observation should be considered when planning the follow-up for these patients after first-line treatment.

The role of surgery in platinum-resistant ovarian cancer: A call to the scientific community.

In the last decade, a growing attention has been focused on identifying effective therapeutic strategies also in the orphan clinical setting of women with platinum-resistant disease. In this context, secondary cytoreductive surgery (SCS) remains a potential approach only in women with platinum sensitive relapse, but experimental data have been published supporting the role of SCS also in patients with platinum-resistant recurrence. In particular, surgery is emerging as a potential option in specific subgroups of women, such as those patients with low-grade serous histology, or low-volume relapse with disease located in the so-called pharmacological sanctuaries. Furthermore, contrasting evidences have suggested a potential role in this clinical setting of SCS combined with intraperitoneal hyperthermic chemotherapy. In this complex scenario we review here the available evidences regarding the role surgery in ovarian cancer patients with platinum resistant disease, trying also to understand which patients may benefit from this challenging, experimental approach.

Use of ablation and ultrasonic aspiration at primary debulking surgery in advanced stage ovarian, fallopian tube, and primary peritoneal cancer

ObjectivesOvarian cancer patients with miliary disease have the lowest rates of complete surgical resection and poorest survival. Adjunct surgical techniques may potentially increase rates of complete surgical resection. No studies...

Maximal-Effort Cytoreductive Surgery for Ovarian Cancer Patients with a High Tumor Burden: Variations in Practice and Impact on Outcome

BackgroundThis study aimed to compare the outcomes of two distinct patient populations treated within two neighboring UK cancer centers (A and B) for advanced epithelial ovarian cancer (EOC).MethodsA retrospective analysis of all new stages 3 and 4 EOC patients treated between January 2013 and December 2014 was performed. The Mayo Clinic surgical complexity score (SCS) was applied. Cox regression analysis identified the impact of treatment methods on survival.ResultsThe study identified 249 patients (127 at center A and 122 in centre B) without significant differences in International Federation of Gynecology and Obstetrics (FIGO) stage (FIGO 4, 29.7% at centers A and B), Eastern Cooperative Oncology Group (ECOG) performance status (ECOG < 2, 89.9% at centers A and B), or histology (serous type in 84.1% at centers A and B). The patients at center A were more likely to undergo surgery (87% vs 59.8%; p < 0.001). The types of chemotherapy and the patients receiving palliative treatment alone were equivalent between the two centers (3.6%). The median SCS was significantly higher at center A (9 vs 2; p < 0.001) with greater tumor burden (9 vs 6 abdominal fields involved; p < 0.001), longer median operation times (285 vs 155 min; p < 0.001), and longer hospital stays (9 vs 6 days; p < 0.001), but surgical morbidity and mortality were equivalent. The independent predictors of reduced overall survival (OS) were non-serous histology (hazard ratio [HR], 1.6; 95% confidence interval [CI] 1.04–2.61), ECOG higher than 2 (HR, 1.9; 95% CI 1.15–3.13), and palliation alone (HR, 3.43; 95% CI 1.51–7.81). Cytoreduction, of any timing, had an independent protective impact on OS compared with chemotherapy alone (HR, 0.31 for interval surgery and 0.39 for primary surgery), even after adjustment for other prognostic factors.ConclusionsIncorporating surgery into the initial EOC management, even for those patients with a greater tumor burden and more disseminated disease, may require more complex procedures and more resources in terms of theater time and hospital stay, but seems to be associated with a significant prolongation of the patients overall survival compared with chemotherapy alone.

Incorporation of HIPEC into a high volume ovarian cancer program: Initial results and outcomes.

e17040 Background: HIPEC showed a progression free survival when incorporated into interval cytoreductive surgery for ovarian cancer patients in a recent phase lll trial. This has led to a paradigm shift at many institutions and the consideration of HIPEC. The goal of this study is to report on the initiation of this program and change in practice at a high volume cancer center over a period of 1 year. Methods: Reviewed surgical cases from 1/2018 through 1/2019 where patients were thought to have a primary ovarian or fallopian tube cancer. Variables included age, stage, histology, primary or interval debulking surgery, number of neoadjuvant (NAJ) chemotherapy cycles. HIPEC patients were selected out and variables examined included intraoperative procedures, optimal cytoreduction, type of chemotherapy administered, postoperative complications, and ability to receive consolidation chemotherapy. Results: 35 cases where ovarian cancer known or suspected preoperatively. 23 patients had primary surgery consisting of tah/bso/surgical staging/tumor debulking. 0/23 of these patients were offered HIPEC chemotherapy as an upfront strategy. 12 patients received neoadjuvant chemotherapy for recurrent (2) or advanced (10) disease. 11/12 of these patients proceeded to an interval surgery. 6/11 (54%) were planned for HIPEC. This was aborted in 1/6 because of thrombocytopenia. 5/6 patients went on to receive HIPEC. They received 3-6 cycles of NAJ chemotherapy, platinum and taxane. 3/5 also received preoperative Avastin. All had R0 resection. 1 patient had a bowel resection. Either carboplatin or cisplatin was used for HIPEC over 90 minutes. 2/5 patients had postoperative G2-3 cytopenias. 3/5 patients were able to receive consolidation chemotherapy, 2 of them within six weeks of surgery and with Avastin containing regimens. Conclusions: In a large volume center initiating a HIPEC ovarian cancer program in less than one years’ time, HIPEC was offered to 50% of patients undergoing interval debulking for Stage III or IV serous ovarian cancer after NAJ chemotherapy and in rare cases for patients with recurrent cancer planned for cytoreduction. Patients may go on to receive postoperative chemotherapy but may have prolonged cytopenias and consolidation therapy delays. HIPEC was not incorporated into an upfront surgical strategy.[Table: see text]

Modeled CA-125 kinetics during neoadjuvant chemotherapy for predicting the likelihood of optimal interval debulking surgery in ovarian cancer patients: Data from CHIVA trial (a GINECO study).

5546 Background: A pre-operative predictive biomarker of CC0 interval debulking surgery (IDS) likelihood would be helpful. The modeled CA125 elimination rate constant KELIM predicts OS in 1st line setting (You et al. Clin Cancer Res 2019). The predictive/prognostic values of KELIM regarding CC scores at IDS, and survivals, during neo-adjuvant chemotherapy were assessed. Methods: The data of the CHIVA randomized phase II trial, comparing carboplatin-paclitaxel +/- nintedanib before IDS (NCT01583322), were used. A semi-mechanistic model was built to describe CA125 longitudinal kinetics during the first 100 treatment days. The relationships between KELIM and IDS CC scores, PFS &amp; OS, were assessed with other major prognostic factors (grade, histology, GCIG CA125 response, FIGO stage, and arm) using multivariate logistic regression (logit), C-index &amp; survival tests. Results: The longitudinal kinetics of 529 CA125 values, assessed every 3 weeks during neo-adj chemotherapy, were modeled in 133 patients (out of 188). KELIM (as a continuous covariate) was the only significant predictive factor of CC0 IDS likelihood using multivariate analyses (OR = 12.37, 95% CI [4.32-39.67]). CC0 IDS probability can be estimated with patient KELIM: ≥ 90 % if standardized KELIM ≥ 0.12. Non-parametric survival models confirmed the independent predictive values of KELIM categorized by terciles regarding PFS &amp; OS (Table). The parametric model linking KELIM (as a continuous covariate) with OS allows to predict the patient survivals (months) based on their estimated KELIM (HR = 0.20, [0.10-0.39]). Conclusions: The prognostic &amp; predictive values of the modeled CA125 KELIM are also confirmed regarding CC0 IDS likelihood, PFS and OS with neo-adjuvant chemotherapy. Patient KELIM is calculable online, based on observed CA125 values, on http://www.biomarker-kinetics.org/ . Clinical trial information: 2011-006288-23. [Table: see text]

Hubungan Kadar CA-125 Praoperatif terhadap Prognosis Survival Penderita Kanker Ovarium Epitelial di RSUP Dr.Sardjito

Background: CA-125 level increases in 50% of patients with stage I, 90% of patients with stage II, 92% of patients with stage III and 94% of patients with stage IV ovarian cancer. CA-125 level were not a diagnostic tool to detect ovarian cancer, however it was useful to monitor the progressive of disease and as a prognostic marker.Objectives: The aim of this study is to prove whether CA-125 level before surgery in ovarian cancer patients at Dr. Sardjito Hospital as well as a factor that correlates to the survival prognosis of those patients.Method: This research used cohort retrospective study at Dr. Sardjito Hospital Yogyakarta.Result and Discussion: As much as 71 ovarian cancer patients which had been included in this research with inclusion and exclusion criteria. Subjects were divided into two groups. One group was for patients with low CA-125 level (≤35 U/ml) as much as 18 subjects and another group was for patients with high CA-125 level (&gt;35 U/ml) as much as 53 subjects. The result of a bivariate analysis with an independent survival analysis (Cox’s Regression) was the stage of disease (p=0.005, HR 4.827, CI 95% 1.623 – 14.355) and residual tumour (p=0.029, HR 2.605, CI 95% 1.101 – 6.161) were a survival prognosis factor. Multivariate analysis with a survival analysis (Cox’s Regression) shows CA-125 level (p=0.031, HR 4.131, CI 95% 1.143 – 14.933) and menarche (p=0.003, HR 4.989, CI 95% 1.736 – 14.342) were significantly related with survival prognosis in EOC (Epithelial Ovarian Cancer) patients at Dr. Sardjito Hospital.Conclusion: CA-125 level affects the survival rate of epithelial ovarian cancer patients in Dr. Sardjito Hospital. Besides the level of CA-125, there are other factors that affect the survival rate of epithelial ovarian cancer patients which is the stage of cancer, residual operation and age of menarche.Keywords: CA-125 level, EOC, prognosis, survival.

Increased RHAMM expression relates to ovarian cancer progression

BackgroundElevated hyaluronan-mediated motility receptor (RHAMM) has been reported to contribute to disease progression, aggressive phenotype and poor prognosis in multiple cancer types, however, RHAMM’s role in ovarian cancer (OC) has not been elucidated. Therefore, we sought to evaluate the role for RHAMM in epithelial OC.ResultsDespite little to no expression in normal ovarian surface epithelium, western immunoblotting, immunohistochemical staining and enzyme linked immunosorbent assay showed elevated RHAMM levels in clinical tissue sections, omental metastasis and urine specimens of serous OC patients, as well as in cell lysates. We also found that RHAMM levels increase with increasing grade and stage in serous OC tissues and that RHAMM localizes to the apical cell surface and inclusion cysts. Apical localization of RHAMM suggested protein secretion which was validated by detection of significantly elevated urinary RHAMM levels (p < 0.0001) in OC patients (116.66 pg/mL) compared with normal controls (8.16 pg/mL). Likewise, urinary RHAMM levels decreased following cytoreductive surgery in OC patients suggesting the source of urinary RHAMM from tumor tissue. Lastly, we validated RHAMM levels in OC cell lysate and found at least 12× greater levels compared to normal ovarian surface epithelial cells.ConclusionThis pilot study shows, for the first time, that RHAMM may contribute to OC disease and could potentially be used as a prognostic marker.

INDICATIONS FOR DIAGNOSTIC LAPAROSCOPY IN VARIOUS STAGES OF TREATMENT OF PATIENTS WITH OVARIAN CANCER

The experience in performing laparoscopic surgery for ovarian cancer patients was analyzed. Laparoscopic surgery with biopsy is currently the optimal diagnostic technique before starting systemic treatment in patients with advanced ovarian cancer. This procedure allows not only to obtain morphological verification but also to evaluate the extent of ovarian cancer involvement and its respectability. Laparoscopy is preferred over laparotomy because of its minimally invasive nature and shorter healing time, with comparable results in terms of the surgical outcomes and oncological safety.

Complications associated with 9–10 Fr venous access port use in adjuvant intraperitoneal chemotherapy after a cytoreductive surgery in ovarian cancer patients

PurposeTo determine the complication rate associated with using a single-lumen intravenous access port with a silicone catheter of 9–10Fr size in the intraperitoneal treatment, including hyperthermic intraperitoneal chemotherapy, in ovarian cancer. Patients/methodsWe reviewed 27 patients who had subcutaneous venous access ports placed for the administration of IP chemotherapy. With four patients, the catheter was implanted during a hyperthermic intraperitoneal chemotherapy-related laparotomy using the closed technique. Each case was categorized as to the number of cycles of IP therapy received. ResultsSeven catheter-related complications were noted. These were divided into two categories: six malfunctions (24%) and one infection (4%). Overall, of the patients who had IP catheters placed and received IP chemotherapy, 13 (54.2%) were able to complete the six regimens. Among the four (14.8%) patients who had the catheters planted directly following the HIPEC, one experienced a catheter leak, one an infection and one concluded the treatment successfully; one is still being treated. ConclusionsA subcutaneous single-lumen intravenous access port with a silicone catheter of a large size (9–10Fr) is related to a lower rate of catheter-related complications than previously reported open-ended Tenckhoff catheter treatment. An additional advantage is the possibility of removing the catheter as an office procedure under local anesthesia. Intraperitoneal chemotherapy following a HIPEC procedure may cause increased occurrence of catheter-related complications. As of 2010 we have been using silicone subcutaneous catheters in our center.

Specialist surgery for ovarian cancer in England

ObjectiveThe aim of this study is to evaluate the impact of the 1999 national recommendations for ovarian cancer surgery in England to be performed by specialist surgeons in specialist centres. MethodsA retrospective analysis of English cancer registry records, Hospital Episode Statistics (HES) data for all English NHS providers and General Medical Council (GMC) sub-specialty accreditation, to consider changes to the annual proportion of ovarian cancer (ICD10 C56-C57) patients undergoing major gynaecological surgery in gynaecological cancer centres (GCCs) or by specialist gynaecological oncologists (GOs). ResultsFrom 2000 to 2009, 2428 consultants were responsible for surgery on 30,753 patients. There were significant increases in the proportions of patients undergoing surgery at GCCs (43% to 76%, P<0.001), by GMC accredited GOs (5% to 36%, P<0.001), and by high ovarian cancer caseload (≥18 cases) surgeons (22% to 56%, P<0.001). ConclusionThere have been increased centralisation and specialisation of surgery for ovarian cancer patients since the NHS Cancer Plan (2000) and there has also been improved survival. However, by 2009, many ovarian cancer patients were still not receiving specialist surgery; the majority of patients were not operated on by GMC accredited gynaecological oncologists and there was considerable regional variation. Systems of accreditation should be reviewed and trusts should ensure that HES data accurately records clinical activity.

Abstract 4937: Fluorescence imaging using Clostridium Perfringens Enterotoxin carboxi-terminal fragment (c-CPE) to target metastatic chemotherapy-resistant human ovarian cancer in xenograft mice

Abstract Epithelial ovarian cancer is the most lethal gynecologic malignancy. It is treated through up front surgery followed by chemotherapy or with neoadjuvant chemotherapy before surgical debulking. Achieving complete or optimal cytoreduction improves both progression free and overall survival. In the operating room, no matter the care taken, there is the potential for areas of macroscopic, microscopic and occult metastases to remain unvisualized. The development of a sensitive and specific intraoperative system for the visualization and removal or destruction of metastatic disease may improve patient outcome. Fresh ovarian cancer samples were recently analyzed by our group with genetic fingerprinting. This analysis revealed high expression of claudin-3 and -4, the epithelial receptors for Clostridium Perfringens Enterotoxin (CPE). Although the administration of the full length CPE in mice is toxic, the injection of the only carboxi-terminal fragment (c-CPE) avoids toxicity while preserving the binding to the receptors. Our previous data showed specific binding of FITC conjugated c-CPE (FITC-c-CPE) to primary ovarian cancer cell lines in vitro as well as preferential accumulation of the labeled peptide into ovarian cancer xenografts in vivo. This study evaluates the in vivo distribution of FITC-c-CPE after intraperitoneal (IP) injection of the peptide as well as the kinetics and tumor binding capacity of c-CPE conjugated to the NearInfraRed Dye CW800 (CW800-c-CPE), focusing on the ability of CW800-c-CPE to identify metastases of chemotherapy-resistant ovarian cancer overexpressing claudin-3 and -4 in vivo. We found that fluorescence uptake by the tumor starts 30 minutes after FITC-c-CPE injection with negligible staining of healthy organs. When the abdominal cavity of FITC-c-CPE injected mice was visualized using a fluorescence microscope, strong signal was detected in near microscopic metastatic nodules and in malignant tumor spheroids isolated from the ascites. Similarly, CW800-c-CPE also accumulated in tumors in vivo following IP or systemic (IV) injection. Ex vivo distribution analysis demonstrated a significantly higher mean fluorescence intensity (MFI) in tumor compared to healthy organs (MFI: mean ± STDV: 156.55 ± 23.73, 95.72 ± 18.19, 30.68 ± 5.88, 23.33 ± 4.05, 34.71 ± 12.71, 28.16 ± 6.1413.46 ± 1.35, 19.78 ± 5.43 in the tumor, kidney, liver, spleen, bowel, lungs and brain, respectively; p&amp;lt;0.01). The accumulation of CW800-c-CPE was also noted in small size tumor implants in the abdomen. These data suggest that c-CPE has tremendous specificity for targeting metastatic chemotherapy-resistant ovarian cancer in vivo. Furthermore, the c-CPE peptide has the potential to be implemented into the operative setting to allow for improved detection of residual tumor during staging and cytoreductive surgery for ovarian cancer patients. Citation Format: Emiliano Cocco, Sara Gasparrini, Erik M. Shapiro, Carlton Schwab, Stefania Bellone, Ileana Bortolomai, Salvatore Lopez, Natalia J. Sumi, Elena Bonazzoli, Roberta Nicoletti, Yang Deng, William M. Saltzman, Caroline J. Zeiss, Dan-Arin Silasi, Thomas J. Rutherford, Peter E. Schwartz, Alessandro D. Santin. Fluorescence imaging using Clostridium Perfringens Enterotoxin carboxi-terminal fragment (c-CPE) to target metastatic chemotherapy-resistant human ovarian cancer in xenograft mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4937. doi:10.1158/1538-7445.AM2014-4937

Secondary debulking surgery in ovarian cancer patients with isolated nodal recurrence located in the region above and behind the renal vein

ObjectiveWe describe our early experience with a suprarenal and retrorenal para-aortic lymphadenectomy involving the mobilization of the left kidney. MethodsThree patients with isolated nodal recurrence located in the region above and behind the renal vein underwent the removal of these metastatic lymph nodes using a left renal mobilization procedure. Results and conclusionThe enlarged suprarenal and retrorenal lymph nodes were safely and effectively removed in all 3 patients. Postoperatively, a lymphatic fistula developed in one patient. However, no morbidities related to renal mobilization, including renal ischemia, were observed in the current series. A further large, prospective study is required to evaluate this surgical procedure.

Involvement of Gynecologic Oncologists in the Treatment of Patients With a Suspicious Ovarian Mass

To identify the factors associated with inclusion of a gynecologic oncologist in managing the care of a woman with suspected ovarian cancer. A vignette-based survey was mailed to 3,200 physicians aged 64 and younger who were randomly sampled from family physician, general internist, and obstetrician-gynecologist (ob-gyn) lists from the American Medical Association Physician Masterfile. The vignette described a 57-year-old woman with pain, bloating, and a suspicious right adnexal mass with ascites. Using multivariable analysis we evaluated patient, physician, and practice characteristics associated with a self-reported referral or inclusion of a gynecologic oncologist in the patient's care. The response rate was 61.7%. After exclusions we included 569 ob-gyns, 591 family physicians, and 414 general internists. Gynecologic oncologist referral and consultation was self reported by 39.3% of family physicians and 51.0% of general internists (P=.01). Among ob-gyns, 33.7% indicated they would perform surgery and 66.3% recommended consultation or referral. Factors associated with not referring and consulting included patients having Medicaid insurance (family physicians), providers' weekly average number of patients being more than 91 (family physicians and general internists), male sex (family physicians), a rural practice location (general internists), and solo practice (general internists). Factors associated with primary surgical management for ob-gyns were small and remote rural practice locations and Census division. When presented with a patient with a suspicious ovarian mass, the majority of primary care physicians do not self-report direct referral to a gynecologic oncologist. This may contribute to the high rates of noncomprehensive surgery for ovarian cancer patients in the United States. II.