Jacob M. Estes

Role of chemotherapy for patients with recurrent platinum-resistant advanced epithelial ovarian cancer: A cost-effectiveness analysis.

Current chemotherapy in platinum‐resistant ovarian cancer patients has demonstrated minimal to no improvements in survival. Despite the lack of benefit, significant resources are utilized with such therapies. Therefore, the objective in the current study was to assess the cost‐effectiveness of salvage chemotherapy for patients with platinum‐resistant epithelial ovarian cancer (EOC).

Lynch Syndrome in Women Less Than 50 Years of Age With Endometrial Cancer

OBJECTIVE: To estimate the frequency of mismatch repair deficiencies associated with hereditary nonpolyposis colorectal cancer, or Lynch syndrome, in women less than age 50 with endometrial cancer. METHODS: Consecutive patients less than age 50 diagnosed with endometrial adenocarcinoma were identified. Available pathologic specimens were freshly sliced, and protein expression for MLH1, MSH2, MSH6, and PMS2 was evaluated by immunohistochemistry. Slides were scored on a semiquantitative method with complete absence of any of the four proteins suggesting a deficiency. All results were confirmed by microsatellite instability testing. RESULTS: Sixty-one pathology specimens were analyzed. Twenty-one (34%) of the tumors had absence of staining of at least one of the four mismatch repair proteins determined by immunohistochemistry and confirmed by microsatellite instability testing. Obese patients were less likely than nonobese patients to have a mismatch repair deficiency (21% versus 59%, respectively). Non-obese patients had a relative risk for a mismatch repair deficiency of 5.5 (95% confidence interval 1.6–19.1; P=.01). CONCLUSION: Many women diagnosed with endometrial cancer before age 50 will have a mismatch repair deficiency discovered by immunohistochemistry and microsatellite instability testing. A number of young women diagnosed with endometrial cancer will require further genetic testing for mismatch repair mutations. LEVEL OF EVIDENCE: III

A phase I study of lapatinib in combination with carboplatin in women with platinum sensitive recurrent ovarian carcinoma

OBJECTIVES To determine the maximum tolerated dose (MTD), spectrum of toxicities, clinical activity, and pharmacokinetics of carboplatin given in combination with lapatinib in women with a first recurrence of platinum sensitive epithelial ovarian carcinoma. METHODS Patients with measurable, platinum sensitive recurrent epithelial ovarian carcinoma were eligible. Cohorts of 3-6 patients were to receive up to 6 cycles of intravenous carboplatin AUC of 6 every 21 days in combination with escalating dosages of oral lapatinib (starting at a dose of 750 mg daily). Toxicity was assessed using NCI CTC for Adverse Events. Clinical response was monitored using RECIST criteria. Pharmacokinetic (PK) analysis was performed for the second cohort of patients. RESULTS Twelve patients were enrolled. No dose limiting toxicity was noted. Two of 6 patients in the first cohort had unanticipated excessive delays in treatment due to non-dose limiting G3 neutropenia. Therefore, the study was modified to reduce the carboplatin dose in the second cohort. The median number of courses administered to the 11 evaluable patients in these two cohorts was 2.8 (range 1-6). Drug-related grade 3 or 4 toxicities included non-dose limiting G4 thrombocytopenia (n=1), and non-dose limiting G3 neutropenia (n=3). Of the 11 patients who received >or=1 course of therapy, 3 (27%) had a partial response, and 3 (27%) had stable disease. The pharmacokinetics of carboplatin were not significantly altered by concomitant administration of lapatinib. CONCLUSIONS This regimen of lapatinib and carboplatin was associated with unacceptable non-dose limiting toxicities, excessive treatment delays and limited clinical responses.

Incidence of mechanical malfunction in low-profile subcutaneous implantable venous access devices in patients receiving chemotherapy for gynecologic malignancies

OBJECTIVE The purpose of this study was to investigate the incidence of mechanical complications associated with low-profile subcutaneous implantable venous access devices in gynecologic oncology patients. METHODS Gynecologic oncology patients with low-profile Port-a-Caths implanted between March 2005 and July 2006 were identified into a computerized database. Patient demographics, operative complications, number of chemotherapy cycles, duration of implantation, and mechanical complications were collected. Primary outcomes included port leakage, catheter fracture, and catheter embolization. RESULTS 112 patients underwent 115 Port-a-Cath placements with low profile single-lumen plastic ports with Groshong-valved catheters. Mean Port-a-Cath indwelling duration was 197 days (range: 4-395) with a mean number of 12 chemotherapy cycles (range 0-64). The cumulative complication rate necessitating removal or replacement was 15%. Of the 14 Port-a-Caths removed, ten (8.7%) were secondary to mechanical malfunction: one for leakage at the port site, two for catheter fracture, and seven for fracture with catheter embolization to the heart or pulmonary vasculature-most commonly the right ventricle. Patients with embolization were asymptomatic and all embolized catheters were successfully retrieved by interventional radiology without complications. CONCLUSIONS The rates of catheter fracture and embolization have previously been reported to be low in patients with subcutaneous Port-a-Caths, and have not been studied in patients receiving low-profile subcutaneous Port-a-Caths. This study suggests that catheter fracture may be more common (8.7%) and must be considered in patients with malfunctioning low-profile Port-a-Caths. Embolized catheters can be removed by interventional radiology without significant adverse affects.

Diagnostic loop electrosurgical excisional procedure for discrepancy: do preoperative factors predict presence of significant cervical intraepithelial neoplasia?

Objective. Although pathological discrepancy between Pap smear and biopsy is an accepted indication to perform a diagnostic loop electrosurgical excision procedure (LEEP), this procedure is not without complications. Our objective was to determine the incidence of cervical intraepithelial neoplasia (CIN) 2,3 and patient factors that increase the likelihood of detecting CIN 2,3. Materials and Methods. We performed a retrospective chart review of patients who underwent a diagnostic LEEP for pathological discrepancy at a university-based colposcopy clinic. Pathological discrepancy is defined as a high-grade Pap smear with a colposcopically directed biopsy of CIN 1 or less. Demographic, cytological, and histological information were collected using a computerized database. The patients were divided into 2 groups (CIN 2,3 and CIN 1 or less) based on the pathology from the LEEP specimen. Patient factors were compared with final pathological results using &khgr;2 test, Student t test, Wilcoxon rank sum test, and multivariate analysis as indicated. Results. A total of 102 patients were identified. Seven patients had normal specimens, 3 had HPV changes, 25 had CIN 1, 29 had CIN 2, and 38 had CIN 3. Thirty-five patients (34%) had CIN 1 or less, whereas 67 patients (66%) had CIN 2,3. The 2 groups were comparable in terms of age (30.4 vs 28.1 years), parity (2.2 vs 1.9), and age of coitarche (16.3 vs 16.4 years). No statistical difference existed between the groups regarding race, smoking status, Pap smear, history of previous cytological abnormality, contraception method, number of previous sexual partners, and HIV status. The majority of patients (75%) had not undergone previous treatment of CIN. The CIN 2,3 group were more likely than the CIN 1 or less group to have had previous treatment or biopsy for CIN (66% vs 34%; p = .004). Univariate (p = .004) and multivariate (p < .001) analysis demonstrated previous treatment of CIN as the only significant factor predicting CIN 2,3. Conclusion. Two thirds of women undergoing a LEEP for pathological discrepancy between Pap smear and cervical biopsy will have CIN 2,3. Women that have had previous treatment of CIN are more likely to have CIN 2,3 detected on their LEEP specimen.

Incidence of port site hernias and/or dehiscence in robotic-assisted procedures in gynecologic oncology patients.

OBJECTIVES The incidence of port site hernia and/or dehiscence using bladeless trocars is 0-1.2%. Robotic surgery uses additional port sites and increases manipulation of instruments, raising the concern for more complications. We sought to characterize the incidence of port site complications following robotic surgery when fascia was not routinely closed. METHODS Robotically-assisted (RA) procedures performed for suspected gynecologic malignancy between 1/2006 and 12/2011 were retrospectively reviewed. Bladeless 12 mm and 8mm robotic trocars were used. Fascial closure was not routinely performed except after specimen removal through the port site. The decision to close the fascia remained at the discretion of the surgeon. RESULTS Data from 842 procedures were included. Mean patient age was 55.6 years. Mean Body Mass Index was 33.6 kg/m(2). RA-total laparoscopic hysterectomy (TLH)± unilateral or bilateral salpingo-oophorectomy (BSO)± lymphadenectomy (LND) accounted for 91.6% of procedures. Final pathology confirmed malignancy in 58.6% of cases, primarily endometrial cancer. In 35 cases, the specimen was removed through the port site; fascia was closed in 54.3% of them and no port site hernias or dehiscences occurred. Only one patient underwent a RA-TLH/BSO/LND for endometrial adenocarcinoma and had a port site dehiscence of the 8mm trocar site. No port site hernias occurred. CONCLUSION Port site hernias and dehiscences are rare in RA gynecologic oncology procedures. When bladeless dilating trocars are used, routine closure of even up to a 12 mm port site is unnecessary, even in cases requiring removal of the specimen through the trocar sites.

Conservative Management of Postoperative Fever in Gynecologic Patients Undergoing Major Abdominal or Vaginal Operations

BACKGROUND To develop a standardized protocol for management of postoperative fever in gynecology patients to decrease unnecessary diagnostic workups and empiric use of antibiotics. STUDY DESIGN A prospective analysis of postoperative gynecology patients identified those who experienced fever (maximum temperature [T(max)] > 100.4 degrees F). Patients were triaged into low- and high-risk groups. High-risk patients were managed independent of the protocol. High-risk criteria included bowel operation, preoperative infection, immunodeficiency, indwelling vascular access, mechanical heart valves, and intensive care unit admissions. Low-risk patients were treated with observation and antipyretics. Patients with persistent or high fever, defined as T(max) > 101 degrees F for > 48 hours, were evaluated and treated based on physical examination findings. RESULTS We evaluated 292 postoperative patients. Forty-seven percent of patients had a final diagnosis of malignancy. Sixty-four patients were high-risk and 33% of these patients experienced fever. Using the standardized protocol, 228 low-risk patients were managed. Thirty-seven of the 228 patients (16%) had fever postoperatively. Nineteen patients had low-grade fever (100.4 to 101 degrees F); none of these patients required antibiotics. Seventeen patients had fever (101.1 to 102 degrees F) and one patient had fever > 102 degrees F. Using the protocol, 6 of 37 patients (16%) were treated with antibiotics for an infectious diagnosis. CONCLUSIONS Although postoperative fever is common in gynecologic patients, the incidence of infection is low (3%). A standardized postoperative fever protocol in low-risk gynecology patients decreases use of empiric antibiotics without compromising morbidity.

Autoclave sterilization of instruments used on women with cervical neoplasia is an effective method of eradicating residual human papillomavirus DNA: a polymerase chain reaction-based evaluation.

Objective: To determine whether autoclave sterilization eradicates human papillomavirus (HPV) DNA on specula and instruments used to treat women with cervical neoplasia. Methods: Specula and instruments used in two referral colposcopy clinics were evaluated to determine the PGMY9/11 primer systems ability to amplify residual HPV DNA. Each speculum and instrument was sampled with a Dacron swab and stored in PreservCyt solution (Cytyc Corporation, Marlborough, MA) at 4°C. DNA amplification was performed under standard conditions with appropriate controls followed by HPV typing using the reverse line blot test (Roche Molecular Systems, Alameda, CA). Once validated, the same polymerase chain reaction method was used on autoclave-sterilized specula and biopsy instruments and heated glass bead- and Cidex bath (Johnson & Johnson, New Brunswick, NJ)-sterilized instruments. All results, with appropriate positive and negative controls, were confirmed in triplicate. Results: A total of 140 instruments (70 used and 70 autoclaved) were sampled for residual HPV DNA. Five samples in the contaminated specula arm were excluded from analysis secondary to insufficient sampling. Of the remaining samples, 52.3% (34/65) of contaminated instruments-both specula and biopsy instruments-had detectable HPV DNA. Fifty-five percent of contaminated biopsy instruments (11/20) were positive and 51.1% of contaminated specula (23/45) were positive. All 70 autoclaved samples (50 specula and 20 biopsy instruments) were negative for residual HPV DNA or &bgr;-globin. One instrument in the glass bead and Cidex group that was presumed sterile was positive for HPV 16 DNA. Conclusions: The PGMY9/11 primer system is an effective method to detect residual HPV DNA. Autoclave sterilization appears to eradicate HPV DNA to levels undetectable with this sensitive assay, whereas heated glass beads followed by Cidex bath appears to be inadequate methods. These results suggest that autoclave sterilization is effective when using nondisposable instruments and should be the method of choice in studies using polymerase chain reaction-based amplification of HPV DNA.

Treatment of chemotherapy-induced anemia in ovarian cancer patients: does the use of erythropoiesis-stimulating agents worsen survival?

Objective Considering the paucity of data relating erythropoiesis-stimulating agent (ESA) use to ovarian cancer survival, our objective was to evaluate the effect of ESA as used for the treatment of chemotherapy-induced anemia (CIA) on survival in ovarian cancer patients. Materials and Methods A multi-institution retrospective chart review was performed on ovarian cancer patients. Data collection included patient demographic, surgicopathologic, chemotherapy, ESA, and survival data. Patients were stratified by ever-use of ESA and were compared using appropriate statistical methods. Results A total of 581 patients were eligible for analysis with 39% (n = 229) patients with ever-use of ESA (ESA-YES) and 61% (n = 352) never-use ESA (ESA-NO). Mean age was 60.4 years with most patients having stage IIIC (60%) of papillary serous histological diagnosis (64%) with an optimal cytoreduction (67%). Median follow-up for the cohort was 27 months. Both ESA-YES and ESA-NO groups were similar regarding age, body mass index, race, stage, histological diagnosis, and debulking status. Compared with the ESA-NO group, ESA-YES patients were significantly more likely to experience recurrence (56% vs 80%, P < 0.001) and death (46% vs 59%, P = 0.002). Kaplan-Meier curves demonstrated a significant reduction in progression-free survival for ESA-YES patients (16 vs 24 months, P < 0.001); however, overall survival was statistically similar between the 2 groups (38 vs 46 months, P = 0.10). When stratifying by ever experiencing a CIA, ESA-YES patients demonstrated a significantly worse progression-free survival (17 vs 24 months, P = 0.02) and overall survival (37 vs 146 months, P < 0.001). Conclusions Our data evaluating the use of ESA as a treatment of CIA in ovarian cancer patients are similar to reports in other tumor sites. Considering that patients who used ESA were more likely to experience recurrence and death and to have decreased survival, the use of ESA in ovarian cancer patients should be limited.

Does a standardized preoperative algorithm of clinical data improve outcomes in patients with ovarian cancer? A quality improvement project.

Objective To evaluate the potential impact of a standardized preoperative algorithm on outcomes of patients with suspected ovarian cancer. Methods From January 1 to December 31, 2013, patients with suspected ovarian cancer were triaged to primary debulking surgery or neoadjuvant chemotherapy/interval debulking surgery (NACT/IDS) based on a comprehensive review of preoperative clinical data as part of a quality improvement project. Demographics, surgical, and postoperative data were collected. Results A total of 110 patients with newly diagnosed ovarian cancer were identified: 68 (62%) underwent PDS with an 85% optimal debulking rate. The 30-day readmission rate was 14.7% with a 2.9% 60-day mortality rate. Forty-two patients (38%) underwent NACT. Two patients (4.8%) died before receiving NACT. Thirty-five patients have undergone IDS with an 89% optimal debulking rate. The 30-day readmission rate was 8.5% with a 5.7% 60-day mortality rate after IDS. Conclusions Although it is difficult to predict which patients will undergo optimal debulking at the time of PDS, surgical morbidity and mortality can be decreased by using NACT in select patients. The initiation of a quality improvement project has contributed to an improvement in patient outcomes at our institution.