Enhanced Recovery After Surgery (ERAS) in gynecologic oncology: System-wide implementation and audit leads to improved value and patient outcomes.

OBJECTIVE: Enhanced recovery pathways have been shown to reduce length of stay without increasing readmission or complications in numerous areas of surgery. Uptake of gynecologic oncology ERAS guidelines has been limited. We describe the effect of ERAS guideline implementation in gynecologic oncology on length of stay, patient outcomes, and economic impact for a province-wide single-payer system. METHODS: We compared pre- and post-guideline implementation outcomes in consecutive staging and debulking patients at two centers that provide the majority of surgical gynecologic oncology care in Alberta, Canada between March 2016 and April 2017. Clinical outcomes and compliance were obtained using the ERAS Interactive Audit System. Patients were followed until 30 days after discharge. Negative binomial regression was employed to adjust for patient characteristics. RESULTS: We assessed 152 pre-ERAS and 367 post-ERAS implementation patients. Mean compliance with ERAS care elements increased from 56% to 77.0% after implementation (p < 0.0001). Median length of stay for all surgeries decreased from 4.0 days to 3.0 days post-ERAS (p < 0.0001), which translated to an adjusted LOS decrease of 31.4% (95% CI = [21.7% - 39.9%], p < 0.0001). In medium/high complexity surgery median LOS was reduced by 2.0 days (p = 0.0005). Complications prior to discharge decreased from 53.3% to 36.2% post-ERAS (p = 0.0003). There was no significant difference in readmission (p = 0.6159), complications up to 30 days (p = 0.6274), or mortality (p = 0.3618) between the cohorts. The net cost savings per patient was $956 (95%CI: $162 to $1636). CONCLUSIONS: Systematic implementation of ERAS gynecologic oncology guidelines across a healthcare system improves patient outcomes and saves resources.

Randomized phase II study of two schedules of topotecan in previously treated patients with ovarian cancer: a National Cancer Institute of Canada Clinical Trials Group study.

PURPOSE: As topotecan is S-phase-specific, its efficacy is likely schedule-dependent. Therefore, a randomized study using a "pick the winner" design was undertaken to compare two schedules in patients with recurrent ovarian cancer. PATIENTS AND METHODS: Patients with recurrent epithelial ovarian cancer previously treated with no more than two separate regimens of chemotherapy, one of which had to be platinum-containing, were randomized to either topotecan 1.5 mg/m2 intravenously (i.v.) over 30 minutes daily for 5 days repeated every 21 days (arm A, the standard arm), or topotecan 1.75 mg/m2 as a 24-hour infusion once a week for 4 weeks repeated every 6 weeks (arm B, the experimental arm). RESULTS: Sixty-six patients were eligible and 63 were assessable for response. The response rate in arm A was 22.6% (95% confidence interval [CI], 9.6% to 41.2%), which was significantly superior to that in arm B, 3.1% (95% CI, 0.1% to 16%) (P = .026). The regimens were not equitoxic, with 94% of patients on arm A experiencing grade 3 or 4 granulocytopenia as opposed to 52% on arm B. CONCLUSION: The weekly 24 hour infusion of topotecan at 1.75 mg/m2 was ineffective in relapsed ovarian cancer. The daily-times-five schedule remains the schedule of choice. As the regimens were not equitoxic, one cannot differentiate between an ineffective schedule and an ineffective dose as the reason for the differing response rates. However, the degree of myelotoxicity that already occurs will preclude any substantially higher dosing with the weekly regimen.

Histologic and clinical significance of atypical glandular cells on pap smears.

OBJECTIVE: To determine the association between atypical glandular cells (AGC) on Pap smear and clinically significant histology, in a large health region. METHODS: A cytologic database of over one million Pap smears was reviewed for a result of AGUS/AGC. Cytologic and histologic follow up was obtained to establish the presence of significant histology. RESULTS: 456 patients available for follow up had AGUS/AGC cytology results (0.043% of all Pap smear results). 197(45.2%) patients had a clinically significant diagnosis including 40 with adenocarcinoma in situ (AIS) of the cervix and 48 with endometrial cancer. CONCLUSION: AGC on a Pap smear is frequently associated with a clinically significant diagnosis.

An analysis of the impact of pathology review in gynecologic cancer.

PURPOSE: To analyze the impact of pathology review in gynecologic malignancies. METHODS AND MATERIALS: For all new gynecologic patients seen between December 2, 1993 and January 4, 1996, we conducted a retrospective chart review to determine if a pathology review by the institute's consultant pathologist changed the diagnosis, and if so whether the change altered patient management. A total of 514 patients were seen, of whom 120 had cervical cancer, 226 had endometrial cancer, 122 had a primary ovarian or peritoneal malignancy, 9 had a vaginal malignancy, 28 had vulvar cancer, and 9 had a miscellaneous gynecologic malignancy. RESULTS: On pathology review the diagnosis changed for 200 of 599 specimens (33%). This altered management for 63 of 514 patients (12%). For patients with cervical cancer, the grade of tumor was the main change in pathologic diagnosis, with occasional change in the presence of lymph vascular invasion. These did not translate into patient management alterations. Eight patients (1.5%) had management alterations. The changes in depth of invasion and vascular invasion altered management for 3 patients. Changes in pap smears resulted in two management alterations, and changes in histologic diagnoses altered management for 3 cases. For endometrial primaries the changes in pathologic diagnosis included grade, depth of invasion, and the presence of cervical involvement. This did alter management in 40 cases (8%). For the ovarian malignancies, the main changes were grade, extent of disease, or histologic classification, some of which (10 patients, 2%) resulted in altered management. One patient with a vaginal lesion had the diagnosis changed, which did alter management. Of the patients diagnosed with vulvar cancer, the pathologic diagnosis changed for 11 patients. This included changes in grade and depth of invasion. This altered management of 2 patients. The remaining miscellaneous gynecologic malignancies had only two diagnosis changes that altered management. CONCLUSIONS: Pathologic review of gynecologic malignancies is justified as it can alter patient management. In addition, the process facilitates cooperation of the multidisciplinary team and provides a valuable educational forum to enhance patient care.

Invasive squamous cell carcinoma of the vagina during pregnancy.

BACKGROUND: Squamous cell carcinoma of the vagina in pregnancy is rare. CASE: A 28-year-old primigravida with antepartum bleeding at 20 weeks' gestation was diagnosed with squamous cell carcinoma after biopsy of a vaginal mass. The histology revealed an invasive grade 3 squamous cell carcinoma of large-cell, nonkeratinizing type. The patient declined pregnancy termination and immediate radiation treatment. She continued to have episodes of vaginal bleeding and was admitted at 30 weeks' gestation. A decision was made in consultation with the neonatal unit to deliver her at 32 weeks' gestation. After corticosteroid treatment, she was delivered by cesarean delivery. Positive pelvic lymph nodes were noted at surgery. Postoperatively, she received external beam radiation and brachytherapy and concurrent cisplatin chemotherapy. She is disease free 3 years from her original diagnosis. CONCLUSION: This case emphasizes the importance of a thorough pelvic examination to assess the vaginal walls and cervix at the first prenatal visit and with any antepartum bleeding episode.

Clinical evaluation of a new two-site assay for CA125 antigen.

As appropriate surgery and chemotherapy can improve both quality of life and survival of patients with ovarian adenocarcinoma, there has been a pressing need for "serodiagnostic" assays to enable close patient monitoring. CA 125 antigen has previously been described as a useful tumor marker of ovarian cancer. This is the first clinical evaluation of a radioimmunoassay using two new monoclonal antibodies, B27.1 and B43.13, that react with separate sites on the glycoprotein marker CA 125. Using the new assay, the majority of patients with clinically or radiologically detectable disease had serum CA 125 antigen levels well above the upper limit seen with random apparently healthy donors, while only three patients who were believed free of disease had elevated levels. Disease progression was associated with increasing values of serum CA 125 antigen, while response to therapy was associated with a steady decline in serum CA 125 antigen levels. Seven patients had steadily rising serum CA 125 antigen levels after initially having normal levels. The mean lead time between rise above normal and clinical or radiological evidence of relapse was 5 months (range 2 to 12 months). The merits of further surgical intervention are illustrated by the serial values of two patients followed after chemotherapy. The assay appears to have value in monitoring response to therapy and in detecting disease relapse at a time when appropriate therapeutic intervention is still possible or likely to be beneficial. Furthermore, monitoring CA 125 antigen was shown to be of benefit in assessing response to chemotherapy in a few patients with metastatic adenocarcinoma of unknown primary, and may be useful in this group of patients in determining those likely to benefit from aggressive chemotherapy.

Early cervical cancer and parametrial involvement: is it significant?

OBJECTIVE: To determine the incidence of parametrial involvement in clinical stage IA and IB1 cervical cancer and whether pelvic lymph node status is a predictor of parametrial status. METHODS: Retrospective review of 120 patients with FIGO stage IA/IB1 cervical carcinoma treated by class II radical abdominal hysterectomy between January 1997 and December 2001 was performed. The parametria were examined for microscopic involvement of parametrial lymph nodes and/or tissue. Continuous variables were compared using Wilcoxon rank sum test, and Fisher's exact test was used to categorical variables. Kaplan-Meier curves were constructed for overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazards model was used to investigate prognostic factors. RESULTS: One hundred ten patients were eligible. Five patients (5%) had positive parametria and 13 patients (12%) had positive pelvic lymph nodes. Four (80%) patients with positive parametria had positive pelvic lymph nodes. The groups did not differ significantly in terms of age (P = 0.92), histology (P = 0.15), or LVSI (P = 0.20). Positive parametria was associated with larger tumor size (3.0 vs. 2.0 cm, P < 0.05), greater depth of invasion (16 mm vs. 5 mm, P = 0.03), and pelvic lymph node metastases (80% vs. 10%, P = 0.001). The only variable that was significant in the proportional hazards model was lymph node status (P = 0.02). After median follow-up of 48 months, there was a significant difference in recurrence (40% vs. 4%, P = 0.03) and RFS (0.0003). CONCLUSIONS: Acknowledging small sample size and retrospective study, positive parametrial involvement in stage IA and IB1 cervical cancer is infrequent. There is a significant association with lymph node status. Thus, there may be a role for less radical surgery combined with pelvic lymphadenectomy in this patient population.

A randomised, double-blind, parallel-group study to compare the efficacy and safety of ondansetron (GR38032F) plus dexamethasone with metoclopramide plus dexamethasone in the prophylaxis of nausea and emesis induced by carboplatin chemotherapy.

A double-blind, parallel-group study in 189 ovarian cancer patients compared the efficacy of ondansetron 8 mg i.v. (OND) and metoclopramide 60 mg i.v. (MET) both in combination with dexamethasone 20 mg i.v. in the prevention of carboplatin-induced emesis. On day 1, complete or major control of emesis (0-2 emetic episodes) was observed in 97% patients from the OND group compared with 74% patients from the MET group (p < 0.001). Similarly, a worst-day analysis over days 1-3 showed complete or major control of emesis in 87% patients (OND) compared wth 66% patients (MET) (p < 0.001). Similar findings in favour of the OND group were observed for nausea grade on day 1 and the worst-day grade during days 1-3. OND was better tolerated than MET. Fewer patients from the OND group (13%) reported adverse events compared with the MET group (21%). Extrapyramidal type symptoms were observed in 6 (6%) patients from the MET group (paraesthesia, involuntary movement of the jaw and tongue, and restlessness), compared with none from the OND group. Ondansetron plus dexamethasone is a highly effective and well-tolerated treatment and is significantly superior to metoclopramide plus dexamethasone in the prevention of carboplatin-induced emesis.

A randomized trial of paracentesis plus intraperitoneal tumor necrosis factor-alpha versus paracentesis alone in patients with symptomatic ascites from recurrent ovarian carcinoma.

PURPOSE: Previous phase I and II studies of intraperitoneal recombinant human tumor necrosis factor-alpha (rhTNF-alpha) suggested a high degree of efficacy in reducing or eliminating ascitic fluid. To more accurately determine the efficacy of this agent, the role of paracentesis versus paracentesis plus intraperitoneal rhTNF-alpha was studied in a randomized trial. PATIENTS AND METHODS: Thirty-nine patients with symptomatic ascites with a volume of > 1000 ml from recurrent epithelial ovarian carcinoma or primary peritoneal carcinoma, which was refractory to standard therapy, were randomized either to receive 0.06 mg/m2 rhTNF-alpha (Knoll, Canada) (the dose determined optimal from phase I and II studies) intraperitoneally after drainage of fluid or to receive drainage alone. A maximum of three treatments were given at weekly intervals. Eighteen patients were randomized to receive rhTNF-alpha. RESULTS: None of 18 evaluable rhTNF-alpha patients had either a complete response (CR) (no clinical evidence of ascites and < 400 ml of fluid on ultrasound) or a partial response (PR) (asymptomatic ascites and < or = 1000 ml of fluid ultrasound). There were no CRs or PRs in the 17 evaluable patients who received drainage alone. The intraperitoneal infusion of rhTNF-alpha was generally well tolerated. Moderate to severe toxicity consisted of pain/discomfort in 42.1%, fever/chills in 36.9%, nausea/vomiting in 10.5%, edema in 10.5%, and hypotension in 5.3% of patients receiving rhTNF-alpha. CONCLUSION: rhTNF-alpha, as given in this study, was not effective in preventing recurrence of ascites in this patient population.