Laparoscopic Assessment to Determine the Likelihood of Achieving Optimal Cytoreduction in Patients Undergoing Primary Debulking Surgery for Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of laparoscopic assessment to determine the likelihood of achieving optimal cytoreduction (OC) in patients undergoing primary debulking surgery (PDS) for ovarian cancer. METHODS: All patients who underwent diagnostic laparoscopy and PDS at our institution from January 2008 to December 2013 were identified. We determined the likelihood of achieving optimal cytoreduction by laparoscopic assessment based on tumor site, pattern of spread, and disease burden. Sensitivity was defined as the number of patients who achieved optimal cytoreduction after laparoscopic assessment divided by the number of patients with disease deemed resectable by laparoscopy. RESULTS: We identified 55 patients during study period. Twenty-one of the 55 patients (38%) were early stage disease. Six (10.9%) patients had disease deemed unresectable and 49 (89.1%) had disease deemed resectable at the time of laparoscopy. OC was achieved in 48 of 49 (97.9%) patients. The sensitivity of laparoscopy in predicting OC was 98% (95% confidence interval, 89.3%-99.9%). The operation was completed laparoscopically in 23 of 49 patients (47%); in 26 of 49 (53%), PDS was performed by laparotomy. There were no port site metastases reported. The rate of postoperative complications was 16%. With a median follow-up of 30 months, the median overall survival was not reached and the 75th percentile for overall survival was 37 months. CONCLUSIONS: Laparoscopy was shown to have a high sensitivity in predicting OC and is a feasible tool in triaging patients with ovarian cancer. Laparoscopy is not associated with adverse surgical outcomes.

Robotic Single-Site and Conventional Laparoscopic Surgery in Gynecology: Clinical Outcomes and Cost Analysis of a Matched Case-Control Study.

STUDY OBJECTIVE: To assess the clinical outcomes and costs associated with robotic single-site (RSS) surgery compared with those of conventional laparoscopy (CL) in gynecology. DESIGN: Retrospective case-control study (Canadian Task Force classification II-2). SETTING: University-affiliated community hospital. PATIENTS: Female patients undergoing RSS or CL gynecologic procedures. INTERVENTIONS: Comparison of consecutive RSS gynecologic procedures (cases) undertaken between October 2013 and March 2014 with matched CL procedures (controls) completed during the same time period by the same surgeon. MEASUREMENTS AND MAIN RESULTS: Patient demographic data, operative data, and hospital financial data were abstracted from the electronic charts and financial systems. An incremental cost analysis based on the use of disposable equipment was performed. Total hospital charges were determined for matched RSS cases vs CL cases. RSS surgery was completed in 25 out of 33 attempts; 3 cases were aborted before docking, and 5 were converted to a multisite surgery. There were no intraoperative complications or conversions to laparotomy. The completed cases included 11 adnexal cases and 14 hysterectomies, 3 of which included pelvic lymph node dissection. Compared with the CL group, total operative times were higher in the RSS group; however, there were no significant between-group differences in estimated blood loss, length of hospital stay, or complication rates. Disposable equipment cost per case, direct costs, and total hospital charges were evaluated. RSS was associated with an increased disposable cost per case of $248 to $378, depending on the method used for vaginal cuff closure. The average total hospital charges for matched outpatient adnexal surgery were $15,450 for the CL controls and $18,585 for the RSS cases (p < .001), and the average total hospital charges for matched outpatient benign hysterectomy were $14,623 for the CL controls and $21,412 for the RSS cases (p < .001). CONCLUSION: Although RSS surgery and CL have comparable clinical outcomes in selected patients, RSS surgery remains associated with increased incremental disposable cost per case and total hospital charges. Careful case selection and judicious use of equipment are necessary to maximize cost-effectiveness in RSS gynecologic surgery.

Safety, feasibility and learning curve of robotic single-site surgery in gynecology.

BACKGROUND: Robotic single-site (RSS) surgery has emerged as a novel minimally invasive approach in gynecology. METHODS: Retrospective cohort study of consecutive RSS gynecologic procedures undertaken between October 2013 and March 2014. RESULTS: The 25 RSS completed cases consisted of 11 adnexal and 14 hysterectomy cases of which three included pelvic lymphadenectomies. Mean age, body mass index and estimated blood loss were 51 years, 25 kg/m(2) , 30 mL in the adnexal group, respectively, and 58 years, 27 kg/m(2) , 96 mL in the hysterectomy group, respectively. Mean console time was 20 and 45 min and mean total operative time was 56 and 93 min in adnexal and hysterectomy cases, respectively. The CUSUM method identified two learning phases with significant reduction in console time after the 7th adnexal case and the 5th hysterectomy. CONCLUSION: When performed by advanced minimally invasive surgeons and in appropriately selected patients, RSS surgery is feasible and safe. Copyright © 2015 John Wiley & Sons, Ltd.

Randomized controlled double-blind trial of transversus abdominis plane block versus trocar site infiltration in gynecologic laparoscopy.

OBJECTIVE: The objective of the study was to determine whether transversus abdominis plane (TAP) block reduces postoperative pain when compared with trocar site infiltration of bupivacaine in gynecological laparoscopy. STUDY DESIGN: This was a prospective, randomized, double-blinded clinical trial using patients as their own controls. Women undergoing gynecologic laparoscopy using a 4-port symmetrical technique were randomly assigned to right- or left-sided TAP block using 30 mL of 0.25% bupivacaine with epinephrine. Two cohorts of patients were studied. Cohort 1 consisted of anesthesiologist-administered ultrasound-guided TAP block. Cohort 2 consisted of surgeon-administered laparoscopic-guided TAP block. In both cohorts, contralateral port sites were infiltrated with an equal amount of bupivacaine in divided doses. All patients received intraoperative acetaminophen and ketorolac. Postoperative abdominal pain was assessed at 1, 2, 4, 6, 8, 12, 18, 24, and 48 hours on the block and contralateral sides, before and after palpation, using the 10 point visual analog scale. A 2 point difference in the reported pain scores was considered clinically meaningful. RESULTS: Eighty-eight patients were eligible for statistical analysis: 45 and 43 patients in cohorts 1 and 2, respectively. In both cohorts, most patients reported equal pain on the block side and local side. In cohort 1, there was a statistically significant difference in mean reported pain scores at 2 hours and across time favoring the ultrasound-guided block; however, this did not reach clinical significance. There was no statistically significant difference found at all other time points or when pain scores were objectively assessed after palpation of the incisions. When comparing laparoscopic-guided block with local infiltration, there was no statistically significant difference in reported mean pain scores at all time points or after palpation. CONCLUSION: As part of this multimodal analgesic regimen, neither block method provided a significant clinical benefit compared with trocar site bupivacaine infiltration.

Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer.

Rigosertib (ON 01910.Na), a synthetic novel benzyl styryl sulfone, was administered to 28 patients with advanced cancer in a Phase I trial in order to characterize its pharmacokinetic profile, determine the dose-limiting toxicities (DLT), define the recommended phase II dose (RPTD) and to document any antitumor activity. Patients with advanced malignant neoplasms refractory to standard therapy were given escalating doses of rigosertib (50, 100, 150, 250, 325, 400, 650, 850, 1,050, 1,375, 1,700 mg/m(2)/24h) as a 3-day continuous infusion (CI) every 2 weeks. An accelerated Fibonacci titration schedule with specified decreases for toxicities was used for escalation until grade ≥2 toxicity occurred. Intrapatient dose escalation was allowed if toxicity was grade ≤2 and the disease remained stable. Plasma pharmacokinetics (PK) and urinary PK assessments were studied in the 1st and 4th cycles. Twenty-nine patients (12 men and 17 women; age 36-87 y with a median of 63 y) were registered, but one died before study drug was given. Twenty-eight patients received a median of 3 cycles of therapy. Most common grade ≥2 toxicities attributable to rigosertib included fatigue, anorexia, vomiting and constipation. DLTs included muscular weakness, hyponatremia, neutropenia, delirium and confusional state. Risk factors for severe toxicities include pre-existing neurological dysfunction or advanced gynecologic cancer after pelvic surgery. Rigosertib pharmacokinetics showed rapid plasma distribution phases and urinary excretion. Elevations in plasma Cmax and AUC due to decreases in plasma clearance were associated with acute grade ≥3 toxicities. Of 22 evaluable patients, 9 (41%) achieved a best overall response of stable disease; all other patients (n=13; 59%) progressed. The median progression-free survival time was 50 days (95% confidence interval [CI]: 37-80 days). Nine (41%) patients survived for over 1 y. In summary, prolonged IV infusions of rigosertib were generally well tolerated. Nine (41%) patients achieved stable disease and 9 (41%) patients survived for over 1 year. The RPTD appears to be 850 mg/m(2)/24hr CI x 3 days. (ClinicalTrials.gov identifier: NCT01538537).

Primary pulmonary carcinoid tumor with metastasis to endometrial polyp.

INTRODUCTION: A carcinoid tumor occurring in the endometrium has been documented in the literature, but there is no report in regard to carcinoid tumor metastasis to endometrium. PRESENTATION OF CASE: We report a case of a malignant carcinoid metastasis to an endometrial polyp. Patient underwent hysteroscopy, and polypectomy. The pathology demonstrated an endometrial polyp containing a 4 mm x 5 mm nodule of metastatic carcinoid tumor, consistent with metastasis from patient's known pulmonary carcinoid. The tumor was morphologically similar to the tumors of the right lung, with similar immune-profile. DISCUSSION: This patient presented with a suspicious pelvic ultrasound. Due to her age, the first priority was to exclude uterine cancer. The endometrial polyp, which was found, had a small focus of metastatic carcinoid tumor. To the best of our knowledge, this finding has not been previously recorded in the literature. Our patient also had a history of metastatic carcinoid tumor to breast. This finding is also very uncommon. CONCLUSION: This is the first case in the literature described a malignant carcinoid metastasis to an endometrial polyp.

Differences in perioperative outcomes after laparoscopic management of benign and malignant adnexal masses.

OBJECTIVE: To compare the feasibility and safety of the laparoscopic management of adnexal masses appearing preoperatively benign with those suspicious for malignancy. METHODS: Retrospective study of 694 women that underwent laparoscopic management of an adnexal mass. RESULTS: Laparoscopic management of an adnexal mass was completed in 678 patients. Six hundred and thirty five patients had benign pathology (91.5%) and 53 (7.6%) had primary ovarian cancers. Sixteen patients (2.3%) were converted to laparotomy; there were 13 intraoperative (1.9%) and 16 postoperative complications (2.3%). Patients divided in 2 groups: benign and borderline/malignant tumors. Patients in the benign group had a higher incidence of ovarian cyst rupture (26% vs. 8.7%, p<0.05). Patients in the borderline/malignant group had a statistically significant higher conversion rate to laparotomy (0.9% vs. 16.9%, p<0.001), postoperative complications (1.9% vs. 12.2%, p<0.05), blood loss, operative time, and duration of hospital stay. The incidence of intraoperative complications was similar between the 2 groups. CONCLUSION: Laparoscopic management of masses that are suspicious for malignancy or borderline pathology is associated with an increased risk in specific intra-operative and post-operative morbidities in comparison to benign masses. Surgeons should tailor the operative risks with their patients according to the preoperative likelihood of the mass being carcinoma or borderline malignancy.

Chylous ascites following robotic lymph node dissection on a patient with metastatic cervical carcinoma.

Chylous ascites is an uncommon postoperative complication of gynecological surgery. We report a case of chylous ascites following a robotic lymph node dissection for a cervical carcinoma. A 38-year-old woman with IB2 cervical adenocarcinoma with a palpable 3 cm left external iliac lymph node was taken to the operating room for robotic-assisted laparoscopic pelvic and para-aortic lymph node dissection. Patient was discharged on postoperative day 2 after an apparent uncomplicated procedure. The patient was readmitted the hospital on postoperative day 9 with abdominal distention and a CT-scan revealed free fluid in the abdomen and pelvis. A paracentesis demonstrated milky-fluid with an elevated concentration of triglycerides, confirming the diagnosis of chylous ascites. She recovered well with conservative measures. The risk of postoperative chylous ascites following lymph node dissection is still present despite the utilization of new technologies such as the da Vinci robot.

Sulforaphane induces growth arrest and apoptosis in human ovarian cancer cells.

OBJECTIVES: Isothiocyanates (ITC) from broccoli and other cruciferous vegetables have long been shown to have chemopreventive properties, as demonstrated in cancer models in rodents. Sulforaphane (SFN) is a major ITC present in broccoli. We examined the effects of SFN on the growth of the OVCAR-3 and SKOV-3 ovarian carcinoma cell lines. METHODS: Cell cycle phase determination was performed using a Coulter flow cytometer. DNA strand breaks in apoptotic cells were measured by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labelling (TUNEL). RESULTS: There was a concentration dependent decrease in cell density. Approximately 50% decrease was observed after 48 h of incubation with SFN (2 µM). Analysis of cell cycle phase progression revealed a decrease in the cell populations in S and G2M phases, with an increase of G1 cell population, indicating a G1 cell cycle arrest. The degree of decrease in the replicating population was concentration and time dependent. Incubation of OVCAR-3 cells in cultures with concentrations of 2, 10 and 50 µM of SFN showed 6, 8 and 17% apoptosis, respectively. In addition, when OVCAR-3 cells were exposed to SFN for various time periods (1, 2 or 3 days), the percentage of cells undergoing apoptosis was directly proportional to the incubation period. In this regard, while 18% of the cells underwent apoptosis after 2 days, 42% of the cells showed apoptosis after 3 days of incubation. CONCLUSIONS: These results clearly demonstrated an effect of SFN in inducing growth arrest and apoptosis in ovarian carcinoma cell lines.

A comparative analysis of 57 serous borderline tumors with and without a noninvasive micropapillary component.

The literature concerning serous borderline tumors with a noninvasive micropapillary component suggests an association with invasive implants. We compared the clinicopathologic features of micropapillary serous borderline tumors (MSBTs) with typical SBTs to determine the following: 1) the importance of focal micropapillary architecture in an otherwise typical SBT, 2) the behavior of low-stage MSBTs, 3) whether high-stage MSBTs are inherently more aggressive than high-stage SBTs, and 4) whether invasive implants are prevalent in an MSBT cohort without referral selection bias. The 57 borderline tumors studied were diagnosed at a university hospital between 1981 and 1998; they included 14 MSBTs, 35 SBTs, and 8 SBTs with focal micropapillary features. None of the specimens were referrals for expert pathologic consultation, thus distinguishing our study group from most of those previously reported. Neither MSBTs nor SBTs were associated with invasive implants at diagnosis (0 of 14 and 0 of 43, respectively). They also did not differ with respect to overall stage at diagnosis, but MSBTs were more frequently bilateral than SBTs (71% versus 23%, p = 0.001). There was an increased risk of recurrence in MSBT versus SBT (3 of 14 versus 1 of 43, p = 0.035), but this was stage related; there was no difference between groups when evaluating recurrence in stage I disease (0 of 8 versus 0 of 27). There was no difference in recurrence or stage at diagnosis between SBTs with focal micropapillary features and other SBTs. There was 100% survival in all groups. We conclude that high-stage MSBTs with noninvasive implants should be considered a subtype of SBTs with an increased risk of recurrence. Stage I MSBTs demonstrate clinical features that are similar to low-stage SBTs. Focal micropapillary architecture (<5 mm) has no bearing on outcome. MSBTs in the general population are not strongly associated with invasive implants.

Vacuum-assisted closure in the treatment of complex gynecologic wound failures.

BACKGROUND: Complex wound failures are a source of significant morbidity and mortality. They are costly and time consuming to treat, and may evolve into chronic, debilitating conditions. Vacuum-assisted closure is a novel wound healing technique applying subatmospheric pressure to wounds to expedite healing. CASES: We report the successful use of vacuum-assisted closure therapy on three patients on a gynecologic oncology service with complex wound failures of various chronicity. In all cases, vacuum-assisted closure therapy was well tolerated and demonstrated efficacy within 48 hours of initiation. CONCLUSION: We conclude that vacuum-assisted closure therapy should be included in the armamentarium of the gynecologist addressing complex wound failures.

Supracervical hysterectomy versus total abdominal hysterectomy: perceived effects on sexual function.

BACKGROUND: Our investigation sought to compare changes in sexual function following supracervical hysterectomy (SCH) and total abdominal hysterectomy (TAH). METHODS: A retrospective chart review was performed to identify all patients who underwent supracervical hysterectomy or total abdominal hysterectomy at a tertiary care center. Patients who met criteria for participation were sent a one page confidential, anonymous questionnaire to assess sexual function experienced both pre- and postoperatively. A total of 69 patients in each group were eligible for participation. A multiple logistic regression model was used to analyze measured variables. RESULTS: Forty-eight percent (n = 33) of women undergoing a SCH returned the questionnaire, while 39% (n = 27) of those undergoing a TAH chose to participate. There were no significant demographic differences between the two groups. Patients who underwent TAH reported worse postoperative sexual outcome than SCH patients with respect to intercourse frequency, orgasm frequency and overall sexual satisfaction (P = 0.01, 0.03, and 0.03, respectively). Irrespective of type of hysterectomy, 35% of patients who underwent bilateral salpingoophorectomy (BSO) with hysterectomy experienced worse overall sexual satisfaction compared to 3% of patients who underwent hysterectomy alone (P = 0.02). CONCLUSIONS: Our data suggest that TAH patients experienced worse postoperative sexual function than SCH patients with respect to intercourse frequency and overall sexual satisfaction. Irrespective of type of hysterectomy, patients who underwent bilateral salpingoophorectomy experienced worse overall sexual satisfaction.