Pamela T. Soliman

Position-related injury is uncommon in robotic gynecologic surgery ☆ ☆☆

OBJECTIVE To assess the rate and risk factors for position-related injury in robotic gynecologic surgery. METHODS A prospective database from 12/2006 to 1/2014 of all planned robotic gynecologic procedures was retrospectively reviewed for patients who experienced neurologic injury, musculoskeletal injury, or vascular compromise related to patient positioning in the operating room. Analysis was performed to determine risk-factors and incidence for position-related injury. RESULTS Of the 831 patients who underwent robotic surgery during the study time period, only 7 (0.8%) experienced positioning-related injury. The injuries included minor head contusions (n=3), two lower extremity neuropathies (n=2), brachial plexus injury (n=1) and one large subcutaneous ecchymosis on the left flank and thigh (n=1). There were no long term sequelae from the positioning-related injuries. The only statistically significant risk factor for positioning-related injury was prior abdominal surgery (P=0.05). There were no significant associations between position-related injuries and operative time (P=0.232), body mass index (P=0.847), age (P=0.152), smoking history (P=0.161), or medical comorbidities (P=0.229-0.999). CONCLUSIONS The incidence of position-related injury among women undergoing robotic surgery was extremely low (0.8%). Due to the low incidence we were unable to identify modifiable risk factors for position-related injury following robotic surgery. A standardized, team-oriented approach may significantly decrease position-related injuries following robotic gynecologic surgery.

Prospective Determination of Prevalence of Lynch Syndrome in Young Women With Endometrial Cancer

PURPOSE Age younger than 50 years at the time of colon cancer diagnosis is often used as a screening criterion for Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome). The purpose of this study was to determine the prevalence of MLH1, MSH2, and MSH6 mutations in an unselected cohort of women diagnosed with endometrial cancer at age younger than 50 years. METHODS A prospective, multicenter study was performed at three institutions. After written consent was obtained, germline mutation testing by full sequencing and large deletion analysis of the MLH1, MSH2, and MSH6 genes was performed. Tumor studies included immunohistochemistry of MLH1, MSH2, and MSH6; microsatellite instability analysis; and hypermethylation of the MLH1 promoter. RESULTS Of the 100 women, nine (9%; 95% CI, 4.2 to 16.4) carried a deleterious germline mutation: seven women with mutations in MSH2, one woman with a mutation in MLH1, and one woman with a mutation in MSH6. Two additional women had molecular studies consistent with the diagnosis of Lynch syndrome. The mean body mass index (BMI) for the entire cohort was 34.4, which is significantly higher than 29.2, the mean BMI for the mutation carriers. Predictors of finding a germline mutation included having a first-degree relative with a Lynch syndrome-associated cancer, endometrial tumor with loss of MSH2 expression, tumors with high microsatellite instability, and lower BMI. CONCLUSION In this prospective study of endometrial cancer patients younger than age 50 years, 9% were found to carry germline Lynch syndrome-associated mutations. In addition to young age of onset, family history, BMI, and molecular tumor studies can improve the likelihood of identifying a Lynch syndrome-associated germline mutation in MLH1, MSH2, and MSH6.

Risk factors for young premenopausal women with endometrial cancer

OBJECTIVE: Endometrial cancer is the most common gynecologic malignancy in the United States. The mean age at diagnosis is 61 years; however, 5–30% of women are aged younger than 50 years at the time of diagnosis. The objective of this study was to conduct a clinical and pathologic review of endometrial cancers diagnosed in premenopausal women aged younger than 50 years, to better identify the risk factors for this subgroup of women. METHODS: We conducted a retrospective cohort study of patients with histologically confirmed endometrial cancer treated at the University of Texas, M. D. Anderson Cancer Center from 1989 to 2003. Clinical characteristics including age, body mass index (BMI), parity, diabetes, and personal or family history of cancer were obtained from the medical record. Pathologic information was obtained from pathology reports. RESULTS: Twelve percent (188/1531) of all patients with endometrial adenocarcinoma were aged younger than 50 years. The mean age at diagnosis was 41 years (range 21–49 years). Mean BMI was 34 kg/m2 (range 18–68); 58% of patients had a BMI of 30 or greater. Fifty-five percent were nulliparous and 39% reported irregular menstrual cycles. The incidence of both diabetes and hypertension was 23%. Thirty-six patients (19%) had synchronous ovarian cancers. CONCLUSION: We found that the majority of patients diagnosed with endometrial cancer at a young age were obese and nulliparous. In addition, we found a high incidence of synchronous primary ovarian cancers in this cohort of young, premenopausal women. LEVEL OF EVIDENCE: III

Her-2/neu Overexpression and Amplification in Uterine Papillary Serous Carcinoma

PURPOSE Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer characterized by early metastasis, resistance to therapy, and a high mortality rate. Little is known about the biology of these tumors. Smaller studies suggest that Her-2/neu may be involved in the tumorigenesis of this disease. The purpose of this study was to evaluate the protein expression and gene amplification of Her-2/neu in UPSC and to determine its prognostic value. PATIENTS AND METHODS Tumor tissue from 68 patients with UPSC treated at The University of Texas M.D. Anderson Cancer Center from 1989 to 2002 was available. Her-2/neu expression was evaluated by immunohistochemistry (IHC). Overexpression was defined as complete membrane staining in greater than 10% of the cells. In tumors with overexpression of Her-2/neu by IHC, fluorescence in situ hybridization (FISH) was performed to assess gene amplification. Clinical and pathologic information was obtained from medical records. RESULTS Twelve (18%) of 68 tumors demonstrated Her-2/neu overexpression. Of these, only two showed gene amplification. When evaluating all 68 patients, Her-2/neu overexpression was associated with a poorer overall survival (OS; P = .008). In our multivariate Cox proportional hazards models, Her-2/neu IHC overexpression, lymph node status, and stage were each associated with OS (P < or = .05). CONCLUSION Positive IHC overexpression of Her-2/neu was seen in 18% of UPSCs but was rarely correlated with Her-2/neu gene amplification. Overexpression of Her-2/neu was associated with a worse overall prognosis. The use of trastuzumab (Herceptin; Genentech, South San Francisco, CA) in women with UPSC should be further evaluated in a clinical trial setting.

A Phase III Randomized Clinical Trial Comparing Laparoscopic or Robotic Radical Hysterectomy with Abdominal Radical Hysterectomy in Patients with Early Stage Cervical Cancer

STUDY OBJECTIVE Cervical cancer is a significant health problem in countries of the developing world. Although case series suggest advantages of total laparoscopic radical hysterectomy (TLRH) compared with total abdominal radical hysterectomy (TARH), no randomized controlled trial is currently available to establish TLRH as the new standard treatment. In this study, TLRH or total robotic radical hysterectomy (TRRH) will be performed without a vaginally assisted portion of the procedure. DESIGN A biphasic randomized controlled trial was designed to test feasibility of recruitment and equivalence in regard to disease-free survival (Canadian Task Force classification I). SETTING Tertiary referral hospital. PATIENTS Patients with histologically confirmed invasive squamous cell carcinoma or adenocarcinoma of the cervix, stage IA1 (with lymphovascular space invasion), IA2, and IB1 are eligible. INTERVENTIONS During the first phase, 100 patients will be randomized (1:1) to receive either TLRH/TRRH or TARH, with the primary end point being the rate of enrollment. During the second phase, recruitment will be extended by another 640 patients in a 1:1 TLRH/TRRH:TARH allocation, to determine equivalence with respect to disease-free survival with 80% power and alpha=0.05. MEASUREMENTS AND MAIN RESULTS Equivalence will be assumed if the difference in disease-free survival does not exceed 7% at 4 years. Secondary outcomes include treatment-related morbidity, costs and cost effectiveness, patterns of recurrence, quality of life, pelvic floor function, feasibility of intraoperative sentinel node sampling, and overall survival. All data from this multicenter study will be entered using online electronic case report forms, allowing real-time assessment of data completeness and patient follow-up. CONCLUSION This prospective trial aims to show the equivalence of a TLRH/TRRH versus TARH approach for patients with early stage cervical cancer following a 2-phase protocol. This trial was developed and designed with the input and approval of the members of the Gynecologic Oncology Committee from the American Association of Gynecologic Laparoscopists.

Phase II Study of Everolimus and Letrozole in Patients With Recurrent Endometrial Carcinoma

PURPOSE The phosphoinositol-3 kinase (PI3K) pathway is frequently dysregulated in endometrial cancer (EC). Hormonal manipulation leads to response in some patients with EC, but resistance derived from PI3K pathway activation has been documented. Targeting mammalian target of rapamycin (mTOR) may overcome endocrine resistance. We conducted a two-institution phase II trial of everolimus and letrozole in women with recurrent EC. PATIENTS AND METHODS Patients were considered incurable, had measurable disease, and were treated with up to two prior cytotoxic regimens. Everolimus was administered orally at 10 mg daily and letrozole was administered orally at 2.5 mg daily. Each cycle consisted of 4 weeks of therapy. Patients were treated until progression, toxicity, or complete response (CR). The primary end point was the clinical benefit rate (CBR), which was defined as CR, partial response, or stable disease (≥ 16 weeks) by RECIST 1.0 criteria. Translational studies were performed to correlate biomarkers with response. RESULTS Thirty-eight patients were enrolled (median age, 62 years; range, 24 to 82 years). Thirty-five patients were evaluable for response. The CBR was 40% (14 of 35 patients); the median number of cycles among responders was 15 (range, seven to 29 cycles). The confirmed objective response rate (RR) was 32% (11 of 35 patients; nine CRs and two partial responses; median, 15 cycles; range, eight to 29 cycles). Twenty percent of patients (seven of 35 patients) were taken off treatment after a prolonged CR and at the discretion of the treating clinician. None of the patients discontinued treatment as a result of toxicity. Serous histology was the best predictor of lack of response. Patients with endometrioid histology and CTNNB1 mutations responded well to everolimus and letrozole. CONCLUSION Everolimus plus letrozole results in a high CBR and RR in patients with recurrent EC. Further development of this combination in recurrent endometrioid EC is under way.

Laparoscopic extraperitoneal para-aortic lymphadenectomy in locally advanced cervical cancer 1

Failure to detect metastasis to para‐aortic nodes in patients with locally advanced cervical cancer leads to suboptimal treatment. No previous studies have prospectively compared positron emission tomography (PET)/computed tomography (CT) with laparoscopic extraperitoneal staging in the evaluation of para‐aortic lymph nodes.BACKGROUND Failure to detect metastasis to para-aortic nodes in patients with locally advanced cervical cancer leads to suboptimal treatment. No previous studies have prospectively compared positron emission tomography (PET)/computed tomography (CT) with laparoscopic extraperitoneal staging in the evaluation of para-aortic lymph nodes. METHODS Sixty-five patients were enrolled; 60 were available for analysis. Patients with stage IB2-IVA cervical cancer without evidence of para-aortic lymphadenopathy on preoperative CT or magnetic resonance imaging (MRI) were prospectively enrolled. All patients underwent preoperative PET/CT. Laparoscopic extraperitoneal lymphadenectomy was performed from the common iliac vessels to the left renal vein. RESULTS The median age at diagnosis was 48 years (range, 23-84). The median operative time was 140 minutes (range, 89-252). The median blood loss was 22.5 mL (range, 5-150). The median length of hospital stay was 1 day (range, 0-4). The median number of lymph nodes retrieved was 11 (range, 1-39). Fourteen (23%) patients had histopathologically positive para-aortic nodes. Of the 26 patients with negative pelvic and para-aortic nodes on PET/CT, 3 (12%) had histopathologically positive para-aortic nodes. Of the 27 patients with positive pelvic but negative para-aortic nodes on PET/CT, 6 (22%) had histopathologically positive para-aortic nodes. The sensitivity and specificity of PET/CT in detecting positive para-aortic nodes when nodes were negative on CT or MRI were 36% and 96%, respectively. Eleven (18.3%) patients had a treatment modification based on surgical findings. CONCLUSIONS Laparoscopic extraperitoneal para-aortic lymphadenectomy is safe and feasible. Surgical staging of patients with locally advanced cervical cancer should be considered before planned radiation and chemotherapy.

Lymphadenectomy during endometrial cancer staging: Practice patterns among gynecologic oncologists

OBJECTIVES Several controversies surround lymphadenectomy for endometrial cancer; surgical approach, who to stage, and the anatomic borders of the lymphadenectomy. The purpose of this study was to identify practice patterns among gynecologic oncologists when performing a lymph node evaluation during staging for endometrial cancer. METHODS A self-administered survey was sent via email to all SGO members on 3 occasions between 2/09 and 4/09. The survey addressed surgical approach, algorithms used to determine staging, and anatomic landmarks defining lymphadenectomy. RESULTS Four hundred and six members (40%) responded. Eighty-two percent completed fellowship and 14% were fellows. Thirty-four percent finished fellowship in 2000 or later. Eighty-five percent educate fellows/residents in either academic (65%) or private practice settings (20%). For a majority of cases 40% prefer laparotomy, 31% perform robotic surgery, and 29% use laparoscopy. Minimally invasive surgery was associated with university-based practice (p=0.048). Most (53%) never/rarely use frozen section to determine whether or not to perform lymphadenectomy. A majority perform staging on all grade 2 and grade 3 cancers (66% and 90%, respectively). When performing paraaortic lymphadenectomy, 50% of respondents use the IMA as the upper border and 11% take the dissection to the renal vessels. Participants who completed fellowship in 2000 or later were less likely to go to the renal vessels (p=0.002). CONCLUSION Current controversies in surgical staging for endometrial cancer are reflected in the practice patterns among gynecologic oncologists. At this point it is unclear if standardizing surgical practice patterns will improve outcomes for patients with endometrial cancer.

Trends in laparoscopic and robotic surgery among gynecologic oncologists : A survey update

OBJECTIVES To assess the use of traditional and robotic assisted laparoscopy by Society of Gynecologic Oncology (SGO) members and to compare the results with those of our published survey in 2004. METHODS Surveys were mailed to SGO members, and anonymous responses were collected by mail or through a web site. Data were analyzed and compared with those of our previous survey. In addition, we gathered information on the effect of robotic assisted surgery on the management of gynecologic malignancies. RESULTS Three hundred eighty-eight (46%) of 850 SGO members responded to the survey. Three hundred fifty-two (91%) indicated that they performed laparoscopic surgery in their practice (compared with 84% in the 2004 survey). The three most common laparoscopic procedures were laparoscopic hysterectomy and staging for uterine cancer (43%), diagnostic laparoscopy for adnexal masses (39%), and prophylactic bilateral oophorectomy for high-risk women (11%). Although 76% of respondents had received either limited or no laparoscopic training during their fellowship, 78% now believe that maximum or much emphasis should be placed on laparoscopic training (55% in the 2004 survey). Twenty-four percent of respondents indicated that they performed robotic assisted surgery, with 66% indicating that they planned to increase their use of the procedure in the next year. CONCLUSIONS We found an overall increase in the use of and perceived indications for minimally invasive surgery in gynecologic oncology among SGO members. Endometrial cancer staging has become an accepted indication for laparoscopy. In addition, most respondents were planning on increasing their use of robotic assisted surgery in the next year.

Safety and feasibility of robotic radical trachelectomy in patients with early-stage cervical cancer

OBJECTIVE This study aimed to determine the safety and feasibility of robotic radical trachelectomy and bilateral pelvic lymphadenectomy. We also describe our surgical technique. METHODS This is a retrospective review of all patients who underwent robotic radical trachelectomy and bilateral pelvic lymphadenectomy from October 2008 to May 2009. We analyzed our data to evaluate the safety and feasibility of this surgery. RESULTS This analysis included 4 patients with early-stage squamous cell carcinoma of the cervix. The median body mass index was 27.1 kg/m(2) (range, 22.7 to 39.1). Three patients had stage IA2 adenocarcinoma; 1 patient had stage IA1 adenocarcinoma with lymph-vascular space invasion. The median operative time was 339.5 min (range, 245 to 416). The median console time was 282.5 min (range, 217 to 338). The median estimated blood loss was 62.5 ml (range, 50 to 75). There were no conversions to laparotomy. There were no intraoperative complications. No patient required blood transfusion. The median length of hospital stay was 1.5 days (range, 1 to 2). One patient experienced a postoperative complication, transient left lower extremity sensory neuropathy. No patient had residual tumor in the trachelectomy specimen, and no patient underwent adjuvant therapy. The median number of pelvic lymph nodes removed was 20 (range, 18 to 27). The median time to a successful voiding trial was 8 days (range, 7 to 9). The median follow-up was 105 days (range, 82 to 217). There were no recurrences. CONCLUSION Robotic radical trachelectomy and bilateral pelvic lymphadenectomy is feasible and safe and should be considered for patients desiring fertility-sparing surgery.