Stabilization of Metastatic Uterine Leiomyosarcoma Using Pembrolizumab.

The estimated 5-year survival rate for patients with stage IV uterine leiomyosarcoma is 29%, with a median survival of <1 year. This report describes a patient with stage IVB leiomyosarcoma who experienced stable disease for 15 months on pembrolizumab. A woman aged 62 years, gravida 2 para 2, with postmenopausal bleeding and a necrotic uterine fibroid underwent a dilation and curettage and was diagnosed with uterine leiomyosarcoma. CT imaging showed pulmonary and bony metastasis. She underwent surgical staging with biopsy-proved stage IVB disease. A mixed partial response was noted using first- and second-line chemotherapy. Molecular tumor profiling confirmed PD-L1 expression. The patient was started on pembrolizumab, and at the time of writing she is status post 23 cycles with stable disease. Pembrolizumab was well tolerated and aided prolonged disease stabilization.

Human ovarian tissue cortex surrounding benign and malignant lesions.

OBJECTIVE: To quantify the number of follicles in patients with ovarian pathologies, benign and malignant, in pregnant and nonpregnant states and to determine how the presence of ovarian masses and BRCA status affects follicular counts. MATERIALS AND METHODS: Slides from 134 reproductive-aged women undergoing oophorectomy were examined using light microscopy by 3 independent counters blinded to the diagnosis. In all, 20 patients had cancer, 69 had benign conditions, and 35 patients were BRCA+ or had a strong family history of breast and/or ovarian cancer. In all, 10 women were either pregnant or immediately postpartum. RESULTS: Patients undergoing risk-reducing surgery had significantly decreased follicle count compared to physiologic control. Patients with cancer had significantly decreased counts compared to all other groups. There were no differences within the benign cohort. CONCLUSIONS: When compared to benign masses, the cortex surrounding an ovarian malignancy has decreased follicle density. The stretch impact may minimize any impact on total follicle numbers. Furthermore, there may be a proliferation of ovarian stroma, with the same number of follicles spread over a larger surface area. This information is important when counseling women with ovarian masses regarding the use of ovarian tissue cryopreservation.

Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma.

OBJECTIVE: We examined the safety and efficacy of combining bevacizumab with albumin-bound (ab-) paclitaxel to treat patients with recurrent, platinum-resistant primary epithelial ovarian or peritoneal carcinoma. METHODS: Patients had measurable disease per RECIST guidelines, progressing within 6 months after a prior course of platinum-based treatment. Patients received ab-paclitaxel 100mg/m(2) given by intravenous infusion over 30 min on days 1, 8, and 15 of a 28-day cycle with bevacizumab 10mg/kg given on days 1 and 15. RESULTS: Forty-eight patients with an average 1.8 prior lines of treatment participated. The overall response rate was 50% (24/48) (95% CI, 34.8% - 65.1%), with 4 complete and 20 partial responses. Fourteen patients (29%) had stable disease, whereas eight (17%) had progressive disease, and two (4%) were not evaluable. Patients received a median of 6 treatment cycles (range, 1 - 31 cycles). The median progression-free survival was 8.08 months (95% CI, 5.78 - 10.15 months); 6 month progression-free rate was 62.5% (95% CI, 47.8%-77.2%); median overall survival was 17.15 months (95% CI, 13.57 - 23.82 months). Grade 3-4 adverse events included gastrointestinal disorders (18.8%), neutropenia (8.3%), and hypertension (6.3%). CONCLUSIONS: Ab-paclitaxel with bevacizumab clearly demonstrates antitumor activity and manageable toxicity profile in patients with recurrent, platinum-resistant ovarian carcinoma. This regimen should be evaluated in a larger randomized trial.

Robotic surgical management of endometrial cancer in octogenarians and nonagenarians: analysis of perioperative outcomes and review of the literature.

The primary aim of this article is to report the outcomes of octogenarians and nonagenarians who have undergone robotic surgery for endometrial cancer. A multi-institutional research consortium was created to evaluate the utility of robotics for gynecologic surgery (benign and malignant). IRB approval was obtained at each institution. A multi-institutional HIPPA compliant database was then created and analyzed for all patients that underwent robotic-assisted surgery with staging for endometrial cancer between the April 2003 and January 2009. In total, 395 patients were identified. A subset of patients between the ages of 80 and 95 years were then identified and analyzed for demographic data and perioperative outcomes. Twenty-seven patients in this age group were identified who underwent robotic-assisted hysterectomy and staging. The median age was 84, and median body mass index was 28. Comorbidities such as diabetes mellitus and hypertension were identified in 22 and 74% of patients, respectively. Over one-half (56%) of the patients reported a prior abdominal surgery. Final pathological analysis demonstrated that 88% of all patients had either Stage I or II disease. The median operative time was 192 min. The median estimated blood loss was 50 cc, and the median lymph node count was 16. The median hospital stay was 1.0 day. The overall intraoperative and postoperative complication rate was 7.4 and 33%, respectively. No patient received a blood transfusion. There was one conversion to laparotomy (3.7%). A comparison of the outcomes of the elderly cohort to those of all patients in the database (control group) revealed that there was no statistically significant difference between the groups in terms of operative time, blood loss, hospital stay, nodal yield, or conversion rate. Intraoperative complications were statistically similar between the groups; however, postoperative complications were significantly higher in the elderly cohort. We conclude that robotic surgery is safe, feasible, and expands surgical options for octogenarians and nonagenarians diagnosed with endometrial cancer. Age should not be considered a contraindication for robotic surgical management of patients with endometrial cancer.

A multiinstitutional experience with robotic-assisted hysterectomy with staging for endometrial cancer.

OBJECTIVE: To report perioperative outcomes and learning curve characteristics from a multiinstitutional experience with robotic-assisted surgical staging for endometrial cancer. METHODS: A multiinstitutional robotic surgical consortium was created to evaluate the usefulness of robotics for gynecologic oncology surgery. An analysis of a multiinstitutional database of all patients who underwent robotic surgery for endometrial carcinoma between April 2003 and January 2009 was performed. Records were reviewed for demographic data and perioperative outcomes. Individual surgeon outcomes were analyzed as well in an attempt to evaluate characteristics of learning with incorporation of robotic technology. RESULTS: Four hundred five patients were identified who underwent robotic surgery for endometrial cancer. Mean age was 62.2 years and mean body mass index was 32.4. Fifty-five percent of patients reported a prior abdominal surgery. Final pathologic analysis demonstrated that 89.6% of all patients had stage I and II disease. Mean operative time was 170.5 minutes. Mean estimated blood loss was 87.5 mL. Mean lymph node count was 15.5. Mean hospital stay was 1.8 days. Intraoperative complications occurred in 3.5% of the patients and conversion to laparotomy occurred in 6.7%. Postoperative complications were reported in 14.6% of the patients. For the group, fewer than 10 cases were required to achieve proficiency with the procedure. CONCLUSION: Robotic technology may level the playing field between the novice and expert laparoscopist for endometrial cancer staging. Prospective trials should be undertaken to compare robotic and laparoscopic approaches to treat endometrial cancer. LEVEL OF EVIDENCE: III.

The impact of robotics on practice management of endometrial cancer: transitioning from traditional surgery.

BACKGROUND: Evaluation of the impact of a new robotic surgery programme on perioperative outcomes for endometrial cancer METHODS: A prospective database of all patients undergoing staging for endometrial cancer during July 2007-July 2008 was collected and analysed. Demographic data and perioperative outcomes were compared between cases performed via laparotomy, laparoscopy and robotics. RESULTS: Sixty-five patients underwent staging during the time of data collection (LAP-26, LSC-7, ROB-32). No difference in surgical volume in the year before vs. after robotics was identified. Median operative time for robotics and laparotomy was significantly less than for laparoscopy (p = 0.023). There was no significant difference in lymph node yields between the three groups (p = 0.92). Robotics was associated with significantly less blood loss (p < 0.0001). Complication rates were significantly lower in the robotic group compared to the laparotomy group (p = 0.05). Median hospital stay was 1 day for the minimally invasive groups. Total number of perioperative inpatient days decreased from 331 to 150 in one year. Practice management of endometrial cancer transitioned from a predominantly open approach (5.6% LSC) to robotics (11% LSC, 49% ROB) within 12 months. CONCLUSIONS: Robotic surgery dramatically altered our management of endometrial cancer and was associated with a significant improvement in several perioperative outcomes when compared to laparotomy and laparoscopy.

Robotic surgery in gynecologic oncology: impact on fellowship training.

OBJECTIVES: To report the impact of a new robotic surgery program on the surgical training of gynecologic oncology fellows over a 12 month period of time. METHODS: A robotic surgery program was introduced into the gynecologic oncology fellowship program at Northwestern University Feinberg School of Medicine in June 2007. A database of patients undergoing surgical management of endometrial and cervical cancer between July 2007 and July 2008 was collected and analyzed. Changes in fellow surgical training were measured and analyzed. RESULTS: Fellow surgical training for endometrial and cervical cancer underwent a dramatic transition in 12 months. The proportion of patients undergoing minimally invasive surgery increased from 3.3% (4/110 patients) to 43.5% (47/108 patients). Fellow training transitioned from primarily an open approach (94.4%) to a minimally invasive approach (11% laparoscopic, 49% robotic, 40% open) for endometrial cancer stagings, and from an open approach (100%) to an open (50%) and robotic (50%) approach for radical hysterectomies. Fellow participation in robotic procedures increased from 45% in the first 3 months to 72% within 6 months, and 92% by 12 months. The role of the fellow in robotic cases transitioned from bedside assistant to console operator within 3 months. CONCLUSIONS: Fellow surgical training underwent a dramatic change with the introduction of a robotic surgery program. The management of endometrial and cervical cancer was impacted the most by robotics. Robotic surgery broadened fellowship surgical training, but balanced surgical training and standardized fellow training modules remain challenges for fellowship programs.

A multi-institutional experience with robotic-assisted radical hysterectomy for early stage cervical cancer.

OBJECTIVE: The purpose of the study is to report a multi-institutional experience with robotic-assisted radical hysterectomy to treat patients with early stage cervical cancer with respect to perioperative outcomes. METHODS: A multi-institutional robotic surgical consortium consisting of five board-certified gynecologist oncologist in distinct geographical regions of the United States was created to evaluate the utility of robotics for gynecologic surgery (benign and malignant). Between April 2003 and August 2008, a total of 835 patients underwent robotic surgery for benign gynecologic disorders and/or gynecologic malignancies by a surgeon in the consortium. IRB approval was obtained and data was collected in a prospective fashion at each institution. For the purposes of the study, a multi-institutional HIPPA compliant database was then created for all patients that underwent robotic-assisted surgery between the April 2003 and August 2008. This database was queried for all patients who underwent a robotic-assisted type II or III radical hysterectomy for Stage IA1 (+vsi)-IB2 cervical carcinoma. Forty-two patients were identified. Records were then reviewed for demographic data, medical conditions, prior abdominal or pelvic surgeries, and follow-up. The perioperative outcomes analyzed included: operative time (skin-skin), estimated blood loss (EBL), length of hospital stay, total lymph node count, conversion to laparotomy, and operative complications. RESULTS: From a database of 835 patients who underwent robotic surgery by a gynecologic oncologist, a total of 42 patients who underwent a robotic-assisted type II (n=10) or type III (n=32) radical hysterectomy for early stage cervical cancer were identified. Demographic data demonstrated a median age of 41 and a median BMI of 25.1. With regard to stage, seven patients (17%) were Stage IA2, twenty-eight patients (67%) were Stage IB1 and six patients (14%) were Stage IB2. There was a single patient with Stage IA1 cervical cancer with vascular space invasion who underwent a type II radical hysterectomy. The overall median operative time was 215 min. The overall median estimated blood loss was 50 cc. No patient received a blood transfusion. The median lymph node count was 25. The median hospital stay was 1 day. Positive lymph nodes were detected in 12% of the patients. Pelvic radiotherapy or chemo-radiation was given to 14% of the patients based on final surgical pathology. Intraoperative complications occurred in 4.8% of the patients and included one conversion to laparotomy (2.4%) and one ureteral injury (2.4%). Postoperative complications were reported in 12% of the patients and included a DVT (2.4%), infection (7.2%), and bladder/urinary tract complication (2.4%) The conversion rate to laparotomy was 2.4%. CONCLUSIONS: Robotic-assisted radical hysterectomy is associated with minimal blood loss, a shortened hospital stay, and few operative complications. Operative time and lymph node yields are acceptable. This data suggests that robotic-assisted radical hysterectomy may offer an alternative to traditional radical hysterectomy. This series contributes to the growing literature on robotic-assisted radical hysterectomy and prospective comparisons with traditional radical hysterectomy are needed.

A comparison of robot-assisted and traditional radical hysterectomy for early-stage cervical cancer.

A robotics surgery program was introduced into the division of gynecologic oncology at Northwestern University Feinberg School of Medicine in June 2007. A prospective database of all patients undergoing a type III radical hysterectomy for stage IB1 cervical cancer between July 2007 and June 2008 was collected and analyzed. Demographic data and perioperative outcomes were analyzed between a traditional and robot-assisted approach. A total of 14 patients were identified who underwent a type III radical hysterectomy for stage IB1 cervical cancer. Seven patients underwent robotic surgery and seven patients underwent traditional surgery. There were no significant differences in median age or body mass index between the two groups. A significant difference in blood loss between robotic (75 cc) and traditional (700 cc) surgery was detected (P = 0.002). A significant difference in hospital stay between robotic (1 day) and traditional (5 days) surgery was observed (P = 0.0007). No significant difference in operative time (260 vs. 264 min) or lymph node yield (19 and 14) was identified between the robotic and traditional approaches. No major operative complications occurred with robotic radical hysterectomy. Robot-assisted radical hysterectomy was associated with a significant reduction in blood loss and hospital stay. Improved nodal yields, fewer operative complications, and less pain was observed with the robotic approach. Robot-assisted radical hysterectomy appears safe and feasible and further investigation is warranted in a prospective fashion.

Outpatient laparoscopic extraperitoneal aortic nodal dissection for locally advanced cervical carcinoma.

The detection of aortic nodal metastasis via radiologic methods is limited with our current technology, although improvements have been made with newer imaging techniques such as positron emission tomography (PET). Surgical staging has shown to alter radiation treatment fields up to 43% of the time in patients with negative preoperative imaging. This limitation has led some investigators to approach the detection of aortic nodal metastasis via a laparoscopic extraperitoneal surgical approach. In this article, we describe step by step our adaptation of this novel minimally invasive procedure for outpatient surgical staging of patients with locally advanced cervical cancer.

Safety, feasibility, and costs of outpatient laparoscopic extraperitoneal aortic nodal dissection for locally advanced cervical carcinoma.

OBJECTIVE: To report on the safety, feasibility, and costs of outpatient laparoscopic extraperitoneal aortic lymph node dissection (LEPSS) for locally advanced cervical carcinoma. METHODS: A retrospective analysis of all outpatient LEPSS procedures performed at our institution between August 2005 and February 2007 was performed. All patients with clinical stage IIB-IVA cervical carcinoma with no evidence of bulky aortic lymphadenopathy (>1.0 cm) on pre-operative computed tomography were offered the procedure. If present, pelvic nodal disease could not exceed greater than 1.5 cm. Records were reviewed for demographics, operative findings, complications, length of stay, and CT scan aortic nodal status. As a comparison, the average costs for outpatient LEPSS and outpatient CT, MRI, and PET scan at our institution were calculated. RESULTS: A total of eighteen outpatient LEPSS procedures were identified. The median age was 49 (22-72). The median BMI was 29 (18-51). The median operative time was 108 min (60-135 min). The median aortic nodal count was 10 (5-20 nodes). The median blood loss was 25 ml (10-50 ml). There were no intraoperative complications. There was no conversion from a retroperitoneal to a transperitoneal approach. No patient required overnight hospitalization. One patient experienced a lymphocyst postoperatively. There was no delay in the initiation of chemoradiation for any of the patients with a median onset of 10 days from the date of surgery. At least 20% of the patients had one or more medical co-morbidities such as obesity, diabetes, hypertension, or a prior abdominal surgery. Occult aortic nodal metastasis was detected in 11% of the patients with a negative pre-operative CT scan. The average calculated costs at our institution for outpatient LEPSS was $5233 dollars versus $1520 dollars for CT scan, $4830 dollars for MRI and $5494 dollars for a PET scan. CONCLUSIONS: To our knowledge this is the first reported experience of outpatient laparoscopic extraperitoneal aortic lymph node dissection for locally advanced cervical cancer. Outpatient LEPSS appears to be a safe and feasible procedure in the hands of an experienced surgeon, however further study is warranted. From a cost analysis perspective, outpatient LEPSS appears equivalent to PET scan and MRI, but is more expensive than CT scan.

Feasibility of laparoscopic extraperitoneal surgical staging for locally advanced cervical carcinoma in a gynecologic oncology fellowship training program.

STUDY OBJECTIVE: Feasibility of laparoscopic extraperitoneal surgical staging for locally advanced cervical carcinoma in a gynecologic oncology fellowship training program. DESIGN: Retrospective analysis (II-2) of all patients who underwent laparoscopic extraperitoneal surgical staging at Women and Children's Hospital for locally advanced cervical cancer between June 2002 and June 2005. SETTING: Gynecologic oncology fellowship training program at a University-County Hospital PATIENTS: Thirty-two patients with clinical stage IIB-IVA cervical carcinoma were identified. INTERVENTIONS: Laparoscopic extraperitoneal surgical staging for clinical stage IIB-IVA cervical cancer. MEASUREMENTS AND MAIN RESULTS: A total of 32 cases of laparoscopic extraperitoneal surgical staging for locally advanced cervical cancer performed by fellows-in-training were identified. Fellows were first assistant surgeon in 10 cases, and operating surgeon in 22 cases. Each fellow was mentored an average of 5 cases as first assistant surgeon. As operating surgeon, all 22 fellow cases (100%) were successfully performed without conversion to laparotomy. Fellow mean operative time was 163 minutes. Fellow mean aortic nodal count was 14. Fellow mean blood loss was 42 mL. The mean hospital stay was 1.6 days. Overall, 2 patients (6.2%) experienced a complication from the procedure. Over one half (53%) of the patients reported a prior abdominal surgery. No lymphedema has been reported in patients who underwent laparoscopic extraperitoneal surgical staging with a median follow-up of 10 months. Surgical comorbidities such as hypertension, diabetes, and obesity were common in the study group. A steep surgical learning curve for the fellows was demonstrated by comparing mean operative times to academic year. Aortic nodal metastasis was detected in 25% of cases, and 14% were occult. CONCLUSIONS: It is feasible to teach laparoscopic extraperitoneal surgical staging to fellows-in-training. Our data suggest that by the end of training, fellows can become proficient with the procedure and are capable of surgical outcomes and complication rates comparable to reported literature.

Prospective randomized controlled trial of fetal fibronectin on preterm labor management in a tertiary care center.

OBJECTIVE: The purpose of this study was to investigate the effect of the rapid fetal fibronectin on the length of hospital stay and the use of preterm labor interventions in a tertiary care center. STUDY DESIGN: Women who were seen in the Labor and Delivery Unit with symptoms of preterm labor were assigned randomly to receive fetal fibronectin (n=46 women) or to preterm labor management without fetal fibronectin (n=51 women). Physicians were not blinded to the result; groups were compared. RESULTS: There was no difference between groups in demographic or obstetric characteristics, the hours spent in labor and delivery, the number of women who were admitted to the antepartum service, the length of stay, or medical interventions. When the results for women with a negative fetal fibronectin test were compared to women with a positive fetal fibronectin test, a significant difference was found in admissions to the antepartum service (P=.032) and the length of stay (P=.008). CONCLUSIONS: A negative fetal fibronectin test was associated with fewer admissions to the antepartum ward and a shorter length of stay.

Implementation of assisted reproductive technologies following conservative management of FIGO grade I endometrial adenocarcinoma and/or complex hyperplasia with atypia.

OBJECTIVE: The objective was to report a series of infertility therapy outcomes following conservative management of endometrial adenocarcinoma and/or complex hyperplasia with atypia. METHODS: A retrospective review of the University of Iowa assisted reproductive technology database was performed. All women presenting with International Federation of Obstetrics and Gynecology (FIGO) grade I uterine adenocarcinoma and/or complex hyperplasia with atypia were assessed for type and duration of medical management, initial, interim treatment, and preinfertility treatment endometrial biopsy (BX) findings. Assessment of infertility treatment outcomes and postinfertility endometrial biopsy findings were performed. All of the pathology samples were re-reviewed at the Gynecologic Oncology Tumor Board to confirm the diagnosis by a pathologist with a particular expertise in gynecologic pathology. RESULTS: Four infertile women, three nulligravid and one primigravid, were evaluated with the diagnosis of FIGO grade 1 endometrial adenocarcinoma and/or complex hyperplasia with atypia desiring to preserve fertility. Two women with FIGO grade 1 endometrial adenocarcinoma were successfully treated with high-dose progestational agents resulting in normal proliferative endometrium. In addition, both women with complex hyperplasia with atypia were successfully treated with progestins and/or ovulation induction. Successful pregnancy outcomes were achieved for three of the four women with assisted reproductive technology. A total of five successful pregnancies and eight healthy live-born infants were achieved among three women. One of the four women was unable to conceive despite three cycles of in vitro fertilization. Hysterectomy was performed for recurrent complex hyperplasia with atypia. In our series, we found it can take 3-10 months (mean, 6.25 months; median, 6 months) to obtain benign endometrium preceding infertility therapy. CONCLUSION: This report demonstrates that conservative management of well-differentiated endometrial adenocarcinoma and/or complex hyperplasia with atypia followed by aggressive assisted reproduction is an option to highly motivated and carefully selected women.

Two successful pregnancies after conservative treatment of endometrial cancer and assisted reproduction.

OBJECTIVE: To report successful pregnancies after conservative management of FIGO grade I adenocarcinoma of the endometrium. DESIGN: Retrospective chart review. SETTING: University-based assisted reproduction and oncology units. PATIENT(S): One patient who had two separate pregnancies. INTERVENTION(S): High-dose progestin (megestrol acetate) therapy for adenocarcinoma, followed by assisted reproduction with donor oocyte. MAIN OUTCOME MEASURE(S): Histologic evaluation of endometrium after megestrol acetate and at completion of childbearing, and successful pregnancies and deliveries. RESULT(S): The patient had complete resolution of adenocarcinoma with progestin therapy and successful delivery of two pregnancies after assisted reproduction. CONCLUSION(S): Conservative management of International Federation of Gynecology and Obstetrics grade I adenocarcinoma of the endometrium allows preservation of childbearing.