Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: Results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial.

OBJECTIVE: To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy. METHODS: PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death. HRQoL was assessed as a prespecified secondary end point using patient-reported responses to the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), the EORTC QLQ Ovarian Cancer Module (EORTC QLQ-OV28), the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), and EQ-5D-5L questionnaires. Assessments were collected at baseline and every 8 weeks (±7 days) for 56 weeks, beginning on cycle 1/day 1, then every 12 weeks (±7 days) thereafter while the patient received study treatment. RESULTS: Among trial participants (niraparib, n = 487; placebo, n = 246), PRO adherence exceeded 80% for all instruments across all cycles. Patients reported no decline over time in HRQoL measured via EORTC QLQ-C30 Global Health Status/QoL and FOSI overall scores. Scores for abdominal/gastrointestinal symptoms (EORTC QLQ-OV28) and nausea and vomiting, appetite loss, and constipation (EORTC QLQ-C30) were higher (worse symptoms) in niraparib-treated patients than placebo-treated patients; except for constipation, these differences resolved over time. Patients did not self-report any worsening from baseline of fatigue, headache, insomnia, or abdominal pain on questionnaires. CONCLUSIONS: Despite some early, largely transient increases in gastrointestinal symptoms, patients with OC treated with niraparib first-line maintenance therapy reported no worsening in overall HRQoL.

Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.

BACKGROUND: Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of BRCA mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown. METHODS: In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival. RESULTS: Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred. CONCLUSIONS: Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016.).

BRCA testing in women with high-grade serous ovarian cancer: gynecologic oncologist-initiated testing compared with genetics referral.

OBJECTIVE: Up to 15% of patients with high-grade serous ovarian, tubal, or peritoneal carcinoma harbor a mutation in BRCA genes. Early notion of mutation status may facilitate counseling, predict prognosis, and increase access to Parp-inhibitors. The aim of this study was to examine the rate of germline genetic testing in a retrospective cohort of women with high-grade serous ovarian, tubal, or peritoneal carcinoma to determine if a new pilot project of gynecologic oncologist-initiated genetic testing improved the rate of testing, after 1 year of implementation. METHODS: Gynecologic oncology-initiated genetic testing was implemented at a single university hospital center with input and collaboration from gynecological oncologists, nurses, and genetic counselors. All patients diagnosed with high-grade serous ovarian, tubal, or peritoneal carcinoma after August 2017 were offered gynecologic oncologist- initiated genetic testing for a panel of 13 hereditary breast and ovarian cancer susceptibility genes. Data from this group was then compared with a historic cohort of patients who received traditional genetic counseling between January 2014 and August 2017 (control group). Patients that had genetic testing through a clinical trial were excluded. The primary outcome was the uptake of genetic testing in both groups. Secondary outcomes included difference in time from diagnosis to genetic result between both cohorts. Data was analyzed using SPSS 25.0 and medians (ranges) were reported. RESULTS: A total of 152 women with high-grade serous ovarian, tubal, or peritoneal carcinoma were included in this study. Between January 2014 to July 2017 there were 108 patients with high-grade serous ovarian, tubal, or peritoneal carcinoma, among which 50.9% (n=54) underwent genetic testing following referral to genetics. The prevalence of BRCA pathogenic variants was 25.9% (14/54): 9.2% (5/54) in BRCA1 and 16.7% (9/54) in BRCA2. The median time from diagnosis to genetics referral was 53 days (range; 3-751), and median time from diagnosis to test result disclosure was 186 days (range; 15-938). After 1 year of implementation of the gynecologic oncologist-initiated genetic testing model, among 44 women diagnosed with high-grade serous ovarian, tubal, or peritoneal carcinoma, 86.2% underwent genetic testing. The median time from diagnosis to result disclosure decreased to 58 days, representing a reduction of 128 days, or 4.27 months (P<0.001). Reasons for non-testing included refusal, death, and follow-up at another hospital. The prevalence of germline BRCA1/2 pathogenic variants was 21% (8/38). CONCLUSION: Gynecologic oncologist-initiated genetic testing at the time of high-grade serous ovarian, tubal, or peritoneal carcinoma diagnosis leads to increased uptake and decreased delays in testing compared with referral for traditional genetic counseling.

Adjuvant therapy in stage III endometrial cancer confined to the pelvis.

OBJECTIVE: To review outcomes of patients with stage III endometrial cancer confined to the pelvis treated with adjuvant pelvic radiotherapy (RT) or sequential chemoradiotherapy (CRT). METHODS: Between 1990 and 2012, 144 patients diagnosed with stage IIIA, B or C1 endometrial cancer were treated in our institution. All were treated with total hysterectomy, bilateral salpingo-oophorectomy ±â€¯lymph node dissection. Post-operatively, 67 patients received adjuvant RT alone, 37 CRT, 21 chemotherapy alone and 19 had no adjuvant therapy. This analysis focuses on the 104 patients treated with RT or CRT. RESULTS: The median follow-up was 61 months. Forty-six patients (44%) were stage IIIA, 6 (6%) were stage IIIB and 52 (50%) stage IIIC1. The 5-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) for patients treated by RT alone vs. CRT were, respectively, 67% vs. 61% (p = 0.55); 67% vs. 51% (p = 0.35); and 76% vs. 65% (p = 0.21). Grade 3 disease was an independent predictor for worse OS (HR = 6.01, p = 0.001), DFS (HR = 3.16, p = 0.03), and DSS (HR = 3.77, p = 0.02). In patients with grade 3 disease (n = 49), the 5-year OS was superior for the CRT (42% vs. 56%, p = 0.007). CONCLUSIONS: In patients with stage III endometrial cancer confined to the pelvis, the addition of adjuvant chemotherapy with RT significantly improved OS in grade 3 disease. Grade 3 histology is a strong predictor for poor outcome. Further randomized studies aiming specifically at stage III disease are warranted.

Clinical significance of isolated tumor cells and micrometastasis in low-grade, stage I endometrial cancer.

INTRODUCTION: Ultrastaging in endometrial cancer (EC) led to increased detection of isolated tumor cells (ITC, ≤0.2 mm) and micrometastases (MM, 0.2-2 mm), with unclear effect on prognosis. Our aim was to characterize the impact of ITC and MM on the outcome of these patients. METHODS: Grade 1 to 2 stage I endometrioid EC patients with nodal ITC (n = 11) or MM (n = 12) between 2012 and 2018 were retrospectively compared to a matched group of lymph node negative (n = 18) patients based on age, body mass index, grade, myometrial invasion, and lymphovascular space invasion (LVI) status using propensity score analysis (1:1). Mann-Whitney U tests were performed on continuous variables and χ2 tests on categorical variables. Progression-free survival (PFS) was the main endpoint. RESULTS: All MM and 81% of ITC had LVI. More ITC/MM patients received RT and chemotherapy (91.7% vs 18.4%; 70.8% vs 4.5%, respectively; P < 0.01) without significant difference in treatment-related toxicities (25% vs 27.3% grade 1%-2% and 20.8% vs 9.1% grade 2-3; P = 0.538) or PFS (29.2 vs 25 months; P = 0.828). Two distant recurrences occurred in MM patients after 2.5 years; one lung and one para-aortic lymph node. CONCLUSION: With adjuvant treatment, ITC/MM in otherwise well-differentiated stage I endometrial cancer have similar outcomes to matched LN- patients.

Laparoscopic Ureteroneocystostomy: Be Prepared!

STUDY OBJECTIVE: To assess the outcomes and complications of laparoscopic ureteroneocystotomy in gynecologic surgery. DESIGN: We retrospectively reviewed all medical records of patients who underwent ureteroneocystostomy between April 2008 and May 2012. DESIGN CLASSIFICATION: Retrospective case series study. SETTING: A university tertiary care hospital. PATIENTS: Nine patients underwent ureteroneocystostomy: 3 patients had ureteral endometriosis stenoses; and 6 patients had iatrogenic ureter injuries. INTERVENTIONS: All procedures were performed laparoscopically. The ureterovesical re-implantation was unilateral in 8 cases and bilateral for 1 patient. MEASUREMENTS AND MAIN RESULTS: The mean operating time was 226.7 min (range, 120-480). Average blood loss was 114.4 mL (range, 30-400). The mean duration of the in-dwelling catheter was 10.4 days (range, 7-21); the average hospital stay was 12.6 days (range, 6-26). The mean duration of the ureteral double J stent was 7.8 weeks (range, 6-16). One patient was re-operated for vaginal and laparoscopic drainage of a pelvic abscess on the sixth postoperative day. The median follow-up time was 20.8 months (range, 9-36), No patient had stenosis or breakdown of a suture line. CONCLUSIONS: Our series confirms the feasibility and the effectiveness of laparoscopic ureteroneocystostomy. This minimally invasive approach, which avoids laparotomy, requires a multidisciplinary team.

Impact of intraperitoneal pressure of a CO2 pneumoperitoneum on the surgical peritoneal environment.

BACKGROUND: Animal experiments have suggested that a high intraperitoneal pressure (IPP) might adversely affect the surgical peritoneal environment. The present experimental study investigates the impact of IPP of a CO(2) pneumoperitoneum on human peritoneum. METHODS: Patients undergoing laparoscopic surgery were subjected to either low (8 mmHg) or standard (12 mmHg) IPP. Normal peritoneum was collected from the parietal wall at the beginning of surgery and every 60 min thereafter. Expression levels of 168 genes that encode extracellular matrix proteins, adhesion molecules or inflammatory cytokine signaling molecules were measured in peritoneal tissues using real-time polymerase chain reaction (PCR)-based assay panels. Human peritoneal mesothelial cells (HPMCs) and human peritoneal fibroblasts (HPFBs) were incubated in a CO(2) insufflation chamber for 1 h at 12 or 8 mmHg. Hyaluronan (HA) synthesis and mRNA expression levels of hyaluronic acid synthases (HAS) and hyaluronidases (Hyal) in HPMCs and HPFBs were measured at 0, 4, 8, 12, 24 and 48 h after CO(2) gas exposure by ELISA and real-time PCR, respectively. RESULTS: Expression levels of connective tissue growth factor (CTGF), matrix metalloproteinase-9, E-selectin, chemokine (C-X-C motif) ligand 2 (CXCL-2), Hyal-1 and Hyal-2 were significantly higher and those of HAS-1, HAS-3, thrombospondin-2 (TSP-2) and interleukin-10 were significantly lower in the 12 mmHg group compared with the 8 mmHg group. HA synthesis was significantly lower in the 12 mmHg group compared with the 8 mmHg group in HPMCs and HPFBs throughout the time course. CONCLUSIONS: A low IPP (8 mmHg) may be better than the standard IPP (12 mmHg) to minimize the adverse impact on the surgical peritoneal environment during a CO(2) pneumoperitoneum.

Ovarian carcinomatosis: how the radiologist can help plan the surgical approach.

Ovarian carcinoma is the most common cause of death due to gynecologic malignancy. Peritoneal involvement is present in approximately 70% of patients at the time of initial diagnosis. The disease spreads abdominally by direct extension, exfoliation of tumor cells into the peritoneal space, and dissemination of tumor cells along lymphatic pathways. Carcinomatosis characterizes an advanced stage of disease in which peritoneal disease has spread throughout the upper abdomen (stage IIIC) or in which diffuse peritoneal disease is accompanied by malignant pleural infiltration or visceral metastases (stage IV). Common sites of intraperitoneal seeding of ovarian carcinoma include the pelvis, omentum, paracolic gutters, liver capsule, and diaphragm. Soft-tissue thickening, nodularity, and enhancement are all signs of peritoneal involvement. Advanced-stage disease is treated either with initial cytoreductive surgery (debulking) followed by adjuvant chemotherapy, or with initial neoadjuvant chemotherapy followed by debulking. Radiologic imaging plays an important role in the selection of patients who may benefit from neoadjuvant chemotherapy before debulking. However, accurate interpretation of the imaging findings is challenging and requires a detailed knowledge of the complex peritoneal anatomy, directionality of flow of peritoneal fluid, and specific disease sites that are likely to present particular difficulties with regard to surgical access and technique. Although there is as yet no clear consensus on the criteria for resectability of peritoneal lesions, extensive involvement of the small bowel or mesenteric root, involved lymph nodes superior to the celiac axis, pleural infiltration, pelvic sidewall invasion, bladder trigone involvement, and hepatic parenchymal metastases or implants near the right hepatic vein are considered indicative of potential nonresectability. Implants larger than 2 cm in diameter in the diaphragm, lesser sac, porta hepatis, intersegmental fissure, gallbladder fossa, or gastrosplenic or gastrohepatic ligament also may represent nonresectable disease.

Impact of intraperitoneal pressure and duration of surgery on levels of tissue plasminogen activator and plasminogen activator inhibitor-1 mRNA in peritoneal tissues during laparoscopic surgery.

BACKGROUND: Our objective was to evaluate the impact of intraperitoneal pressure (IPP) and duration of a CO(2) pneumoperitoneum on the peritoneal fibrinolytic system during laparoscopic surgery. METHODS: Human study: Patients undergoing laparoscopic surgery were divided into two groups: low (8 mmHg, n= 32) or standard (12 mmHg, n= 36) IPP. Normal peritoneum was collected from the parietal wall at the beginning of surgery and every 60 min thereafter. Mouse study: Mice were divided into three groups: low (2 mmHg) or high (8 mmHg) IPP or laparotomy. Peritoneal tissue was collected at 0, 4, 8, 24, 48 and 72 h, and 5 and 7 days after surgery. Real-time RT-PCR was performed in humans and mice to measure the levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) mRNA in peritoneal tissues. RESULTS: Human study: The tPA/PAI-1 mRNA ratio was significantly decreased in the 12 mmHg group at 1 h [P < 0.0001 versus matched initial peritoneal biopsies (MI)]. The tPA/PAI-1 mRNA ratio decreased in both groups at 2 h (P < .0.01 versus MI). Mouse study: The tPA/PAI-1 ratio was decreased at 0 h, and the difference was significant at 4 h in both the laparotomy (P < 0.001 versus controls, 0 h, 5 and 7 days) and high-IPP (P < 0.0001 versus 0, 48 and 72 h, 5 and 7 days) groups. No changes in tPA/PAI-1 ratio were observed in the low-IPP group. CONCLUSIONS: A low IPP and shorter duration of surgery appear to minimally impact the fibrinolytic system during a CO2 pneumoperitoneum.

Comparison between standard and reverse laparoscopic techniques for rectovaginal endometriosis.

BACKGROUND: This study was designed to compare the surgical outcomes of standard and reverse laparoscopic techniques for the treatment of rectovaginal endometriosis. METHODS: A retrospective study was conducted in a teaching and research hospital (tertiary center), which included 75 women subjected to laparoscopic treatment of rectovaginal endometriosis that required both vaginal resection and rectal surgery. Standard and reverse laparoscopic techniques were compared in 35 and 40 women, respectively. Student's t test, Mann-Whitney test, and Fisher's exact test were performed to compare groups when needed; p < 0.05 was considered statistically significant. RESULTS: There was no statistically significant difference in operating time, blood loss, conversion rate, major intraoperative complications, length of hospital stay, and minor postoperative complications between the two techniques. The rate of major postoperative complications for the standard technique was 22.9%, whereas only 5% for the reverse technique (p = 0.02). The rate of postoperative rectovaginal fistula was the same for both techniques. CONCLUSIONS: Major postoperative complications were reduced by using the reverse technique.

Surgical outcomes of laparoscopic hysterectomy for enlarged uteri.

STUDY OBJECTIVE: To compare surgical outcomes of laparoscopic hysterectomy for benign diseases according to the uterine weight. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: Teaching and research hospital, a tertiary center. PATIENTS: Women undergoing laparoscopic hysterectomy for benign diseases. INTERVENTIONS: Patients were divided into three groups according to the uterine weight: <250 g (n = 1300), 250 to 500 g (n = 614), and >500 g (n = 178). MEASUREMENTS AND MAIN RESULTS: Primary outcomes were differences in conversion rates, operating time, and blood loss. Secondary outcomes were differences in length of hospital stay, time to first bowel movement, time of bladder catheterization, and complications. Operating time increased according to the uterine weight (116.5 vs 124.1 vs 133 minutes; p <.001). The rate of conversion was statistically higher only for patients with uteri >500 g (3.3% vs 5% vs 13.5%; p <.001). However, the difference between preoperative and postoperative hemoglobin levels was equivalent for the three groups, as well as the overall rates of minor and major intraoperative complications. There was no difference in the time of bladder catheterization, time to first bowel movement, length of hospital stay, and incidence of minor and major postoperative complications among the three groups. CONCLUSION: Despite longer operating time, there is no increase in the intraoperative or postoperative complication rates in those patients with enlarged uteri undergoing laparoscopic hysterectomy. Only conversion is higher in patients with uteri >500 g.

Long-term follow-up after laparoscopic management of endometrial cancer in the obese: a fifteen-year cohort study.

STUDY OBJECTIVE: To assess the surgical outcomes and long-term results of laparoscopic treatment of endometrial cancer in obese patients, and compare these results with those of nonobese women. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Two referral cancer centers. PATIENTS: Fifty-two obese and 155 nonobese women with clinical stage I endometrial cancer managed by laparoscopy from 1990-2005 in two referral centers. INTERVENTIONS: Demographic, surgical, perioperative and pathological characteristics of obese women and nonobese women with endometrial cancer treated by laparoscopy were analyzed and then compared. Recurrence-free and overall survival was calculated by use of Kaplan-Meier method. MEASUREMENTS AND MAIN RESULTS: Median BMI of the study population was 26.2 Kg/m(2). Median BMI among obese patients was 34.2 Kg/m(2). The conversion rate was independent from the BMI of the patient (3.8% vs 4.5%, p = .80). Neither mean operative time (187.5 vs 172 min, p = .11) neither hospital stay (5.2 vs 4.9 days, p = .44) were related with BMI. Lymphadenectomy was considered not feasible in 7 obese (17%) and 8 nonobese (7%) women (p = 0.09). Fewer lymph nodes were retrieved among obese women (8 versus 11, p <.0002). No differences were found between the groups in terms of perioperative complications. Median follow-up was 69 and 71 months for the obese and nonobese, respectively (p = .59). Overall and disease-free 5-year survival rates did not differ between obese and nonobese patients (90.3% and 87.5% versus 88.5% and 89.8%, respectively). CONCLUSION: Despite some limitations, the laparoscopic approach seems to be particularly useful for obese patients with endometrial cancer, with similar survival and recurrence rates and without any more complications compared to the nonobese population.

[Optical biopsy: the surgical perspective]. / Biopsie optique: le point de vue du chirurgien.

Several new intraoperative imaging techniques, often described under the generic term "optical biopsy", have been developed over the last twenty years. The term optical biopsy in fact covers two distinct approaches. The first is endomicroscopy, which provides the surgeon with histologic images comparable to those obtained by the pathologist in the laboratory. The second is image-guided surgery, which includes a variety of techniques, from fluorescence to sentinel node biopsy and real-time image fusion (enhanced reality). The diagnostic value of intraoperative histology, and the reproducibility of these methods outside the expert centers where they were initially developed, remains to be determined In particular, it remains to be seen whether they can avoid the need for conventional biopsy. The main issue will probably be to decide who is qualified to read these images: a surgeon with training in pathology, or a pathologist who examines images transmitted to the lab or directly in the operating room? Pathologic diagnosis may require several readings of the same slides, additional biopsy sections, or even additional staining procedures. The ability to examine living tissue in situ is a very attractive prospect and will probably represent a major step forward in diagnosis and treatment evaluation. It is difficult to know which of the many candidate techniques will finally be adopted, but the future seems to lie in a combination of image-guided surgery and endomicroscopy.

Incidence of intraabdominal adhesions in a continuous series of 1000 laparoscopic procedures.

OBJECTIVE: The objective of the study was the laparoscopic evaluation of the incidence of intraabdominal adhesions related to prior abdominal surgery. STUDY DESIGN: This was a prospective monocentric study including a continuous series of 1000 gynecologic laparoscopic procedures. Data were collected on history of abdominal surgery. A precise initial description of intraoperative adhesions was performed. RESULTS: Six hundred thirty-seven of the 1000 procedures (63.7%) were performed in patients with a history of 1 or more than 1 abdominal surgery. Intraoperative adhesions were found in 211 of the 1000 subjects (21.10%). Fifty-nine of the 211 cases (28%) involved bowel loops. The prior indication for surgery did not seem to influence adhesion formation. The rate of intestinal adhesions significantly increased with the number of prior abdominal surgeries. The rate of intestinal adhesions was significantly higher in cases of prior midline incisions in comparison with the other incisions. CONCLUSION: Extensive preoperative knowledge of prior surgery is essential to evaluate the risk of adhesion formation.

Carbon dioxide pneumoperitoneum, intraperitoneal pressure, and peritoneal tissue hypoxia: a mouse study with controlled respiratory support.

BACKGROUND: Animal experiments have suggested that the laparoscopic peritoneal environment is hypoxic. This study aimed to investigate whether peritoneal tissue is hypoxic on a cellular level during a carbon dioxide (CO(2)) pneumoperitoneum at different intraperitoneal pressures (IPPs) and to determine the short-term effects of surgical injury on the hypoxia status of peritoneal tissue in the injured peritoneum and the distant noninjured peritoneum at cellular and molecular levels. METHODS: Experiment 1: Mice were divided into five groups according to the following treatments: anesthesia alone, laparotomy, and CO(2) pneumoperitoneum at IPPs of 2, 8, or 15 mmHg. Over the course of each experiment, the peritoneal tissue-oxygen tension (PitO(2)) was continuously monitored. Experiment 2: On the first day, the mice were divided into three groups according to the following treatments: CO(2) pneumoperitoneum at an IPP of either 2 or 8 mmHg or laparotomy. The bilateral caudal epigastric arteries and uterine horns then were coagulated using a bipolar cautery device. On day 7, peritoneal tissue samples were collected for real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. In both experiments, pimonidazole hydrochloride was used to detect tissue hypoxia at a cellular level. RESULTS: Experiment 1: Peritoneal hypoxia at both tissue and cellular levels was detected only in the groups treated with an IPP of 15 mmHg (PitO(2): 5.2 ± 1.0 mmHg, mean ± SEM). Experiment 2: The percentage of pimonidazole immunostained mesothelial and stromal cells from the distant noninjured peritoneum was significantly higher in the group treated with an IPP of 8 mmHg than in the other groups. Hypoxia-inducible factor 1 alpha subunit mRNA expression in the distant noninjured peritoneum of the group treated with an IPP of 8 mmHg was significantly higher than in the control group (anesthesia alone). CONCLUSION: The CO(2) pneumoperitoneum itself did not cause peritoneal hypoxia at either a tissue or a cellular level in a mouse model when a low IPP was used.

Real-world direct healthcare costs of treating recurrent high-grade serous ovarian cancer with cytotoxic chemotherapy.

Aim: To describe the direct healthcare costs associated with repeated cytotoxic chemotherapy treatments for recurrent high-grade serous cancer (HGSC) of the ovaries. Patients & methods: Retrospective review of 66 women with recurrent stage III/IV HGSC ovarian cancer treated with repeated lines of cytotoxic chemotherapy in a Canadian University Tertiary Center. Results: Mean cost of treatment of first relapse was CAD$52,227 increasing by 38% for two, and 86% for three or more relapses with median overall survival of 36.0, 50.7 and 42.8 months, respectively. In-hospital care accounted for 71% and chemotherapy drugs accounted for 17% of the total costs. Conclusion: After the third relapse of HGSC, cytotoxic chemotherapy did not prolong survival but was associated with substantially increased healthcare costs.

Assessment of sentinel nodes for gynecologic malignancies by natural orifices transluminal endoscopic surgery (NOTES): preliminary report.

OBJECTIVE: To assess the feasibility of sentinel lymph node (SLN) biopsy in gynecologic malignancies using natural orifices transluminal endoscopic surgery (NOTES) in an animal model. METHODS: Ten female pigs were operated. Patent blue dye was injected in the paracervical region. The endoscope was introduced through a right lateral colpotomy. Internal iliac vessels were visualized followed by the identification of external iliac vessels. Bilateral dissection was performed to achieve visualization of the aorta and the vena cava. SLN colored in blue were bluntly dissected and then excised. RESULTS: Mean operative time was 56+/-16 minutes. The mean number of SLN retrieved was 1.75+/-1.28. All but one SLN were identified by NOTES procedure. No major complication was observed in this series. A total of 19 SLN were harvested, of which 11 from the left side and 8 from the right side. Fifteen lymph nodes were obtained from the iliac vessels or the promontory and 4 from the lateral aortic or preaortic region. CONCLUSIONS: In this study, we confirmed the feasibility of the SLN technique by NOTES. It can be considered as a potential alternative to reduce morbidity during staging procedures for gynecologic malignancies. Prospective randomized series are necessary to establish the safety and the real benefits of this new technique.

Total laparoscopic radical hysterectomy in the treatment of early cervical cancer.

Total laparoscopic radical hysterectomy (TLRH) has been reported since the early 1990 s. Although the acceptance of TLRH had been slow over the past 15 years, several teams throughout the world have recently reported promising results in the treatment of early cervical cancer with this procedure. Several modifications of the originally described technique have also been reported. From the currently existing data, these is no doubt that TLRH is technically feasible. Its operative safety profile is comparable to that of radical abdominal hysterectomy (RAH), and there exist sufficient data to suggest that the histopathologic outcome is also similar in terms of local radicality and lymph node yield. The duration of the procedure has become acceptable but remains still longer in comparison to RAH, in most series. It is now evident that with increasing experience, repetition, standardization, and incorporation of technological advances, duration can be reduced considerably and become similar to that of RAH. Total laparoscopic radical hysterectomy is associated with less blood loss, faster recovery and return of bowel function, reduced febrile morbidity, and a better cosmetic result. Nevertheless, shorter hospitalization in comparison to that observed after RAH is not consistently reported, and return of normal bladder activity is similar to that observed after RAH. It is also true that the currently existing recurrence and survival data are still immature to draw safe conclusions on its long-term oncological safety. Probably, the time has come for a multicenter randomized study between TLRH and RAH with participation of the institutions with significant experience in this procedure.

Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers.

We report the detection of endometrial and ovarian cancers based on genetic analyses of DNA recovered from the fluids obtained during a routine Papanicolaou (Pap) test. The new test, called PapSEEK, incorporates assays for mutations in 18 genes as well as an assay for aneuploidy. In Pap brush samples from 382 endometrial cancer patients, 81% [95% confidence interval (CI), 77 to 85%] were positive, including 78% of patients with early-stage disease. The sensitivity in 245 ovarian cancer patients was 33% (95% CI, 27 to 39%), including 34% of patients with early-stage disease. In contrast, only 1.4% of 714 women without cancer had positive Pap brush samples (specificity, ~99%). Next, we showed that intrauterine sampling with a Tao brush increased the detection of malignancy over endocervical sampling with a Pap brush: 93% of 123 (95% CI, 87 to 97%) patients with endometrial cancer and 45% of 51 (95% CI, 31 to 60%) patients with ovarian cancer were positive, whereas none of the samples from 125 women without cancer were positive (specificity, 100%). Finally, in 83 ovarian cancer patients in whom plasma was available, circulating tumor DNA was found in 43% of patients (95% CI, 33 to 55%). When plasma and Pap brush samples were both tested, the sensitivity for ovarian cancer increased to 63% (95% CI, 51 to 73%). These results demonstrate the potential of mutation-based diagnostics to detect gynecologic cancers at a stage when they are more likely to be curable.