Pedro T. Ramirez

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.

Comparison of total laparoscopic and abdominal radical hysterectomy for patients with early-stage cervical cancer.

OBJECTIVE: To compare intraoperative, pathologic, and postoperative outcomes of total laparoscopic radical hysterectomy with abdominal radical hysterectomy and pelvic lymphadenectomy for women with early-stage cervical cancer. METHODS: We reviewed all patients who underwent total laparoscopic radical hysterectomy or abdominal radical hysterectomy and pelvic lymphadenectomy between 2004 and 2006. RESULTS: Fifty-four patients underwent abdominal radical hysterectomy, and 35 underwent total laparoscopic radical hysterectomy. Mean age was 41.8 years, and mean body mass index 28.1. There was no difference in demographic or tumor factors between the two groups. Mean estimated blood loss was 548 mL with abdominal radical hysterectomy compared with 319 mL with total laparoscopic radical hysterectomy (P=.009), and 15% of patients who underwent abdominal radical hysterectomy required a blood transfusion compared with 11% who underwent total laparoscopic radical hysterectomy (P=.62). Mean operative time was 307 minutes for abdominal radical hysterectomy compared with 344 minutes for total laparoscopic radical hysterectomy (P=.03). On pathologic examination, there was no significant difference in the amount of parametrial tissue, vaginal cuff, or negative margins obtained. A mean 19 pelvic nodes were obtained during abdominal radical hysterectomy compared with 14 during total laparoscopic radical hysterectomy (P=.001). The median duration of hospital stay was significantly shorter for total laparoscopic radical hysterectomy (2.0 compared with 5.0 days, P<.001). For abdominal radical hysterectomy, 53% of patients experienced postoperative infectious morbidity compared with 18% for total laparoscopic radical hysterectomy (P=.001). There was no difference in postoperative noninfectious morbidity. There was no difference in return of urinary function. CONCLUSION: Total laparoscopic radical hysterectomy reduces operative blood loss, postoperative infectious morbidity, and postoperative length of stay without sacrificing the size of radical hysterectomy specimen margins; however, total laparoscopic radical hysterectomy is associated with increased operative time. LEVEL OF EVIDENCE: II

Vaginal evisceration after hysterectomy: A literature review

The purpose of this review is to highlight the risk factors, clinical presentation, and different surgical management options for vaginal evisceration after vaginal, abdominal, or laparoscopic hysterectomy. We identified all reports of vaginal evisceration after these procedures using sources in the literature from 1900 to the present. We found that a total of 59 patients were reported, 37 (63%) had a prior vaginal hysterectomy, 19 (32%) had a prior abdominal hysterectomy (2 of which were radical hysterectomy), and 3 (5%) had a prior laparoscopic hysterectomy. The majority of these patients were postmenopausal women. Also, the precipitating event was most often sexual intercourse in premenopausal patients and increased intra-abdominal pressure in postmenopausal patients. In addition, the small bowel was the most common organ to eviscerate. Most of the patients presented with vaginal bleeding, pelvic pain, or a protruding mass. We conclude that vaginal evisceration after hysterectomy remains a rare event. It is more often seen after vaginal hysterectomy than after other types of hysterectomy. It can also occur spontaneously or following trauma or vaginal instrumentation, or any event that increases intra-abdominal pressure. Vaginal evisceration represents a surgical emergency, and the approach to therapy for it may be abdominal, vaginal or a combination of the two. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to identify the potential risk factors for vaginal evisceration, to explain the clinical presentation of patients with vaginal evisceration, and to outline the management strategies for patients with vaginal evisceration.

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.

Parametrial involvement in radical hysterectomy specimens for women with early-stage cervical cancer

OBJECTIVE: To estimate the incidence of parametrial involvement and to evaluate factors associated with parametrial spread in women with early-stage cervical cancer and to identify a cohort of patients at low risk for parametrial spread who may benefit from less radical surgery. METHODS: We reviewed all patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between 1990 and 2006. All women with squamous, adenocarcinoma, or adenosquamous disease, stage IA2–IB1, who underwent completed radical hysterectomy were included in the analysis. Normally distributed continuous variables were compared using Student’s t-test for independent samples to analyze the outcome of positive or negative parametrial involvement. RESULTS: Three hundred fifty patients met the inclusion criteria. Overall, 27 women (7.7%) had parametrial involvement. The majority of specimens with parametrial involvement (52%) had tumor spread through direct microscopic extension. Patients with parametrial involvement were more likely to have a primary tumor size larger than 2 cm (larger than 2 cm: 14%, smaller than 2 cm: 4%, P=.001), higher histologic grade (grade 3: 12%, grades 1 and 2: 3%, P=.01), lymphovascular space invasion (positive: 12%, negative: 3%, P=.002), and metastasis to the pelvic lymph nodes (positive: 31%, negative: 4%, P<.001). One hundred twenty-five women (36%) had squamous, adenocarcinoma, or adenosquamous lesions, all grades, with primary tumor size 2 cm or smaller and no lymphovascular space invasion. In this group of patients, there was no pathologic evidence of parametrial involvement. CONCLUSION: We were able to retrospectively identify a cohort of women with early-stage cervical cancer who were at very low risk for parametrial involvement. If prospective application of these findings confirms our results, less radical surgery—such as simple hysterectomy, simple trachelectomy, or conization—with pelvic lymphadenectomy may be a reasonable therapeutic option for women with primary tumors 2 cm or smaller and no lymphovascular space invasion. LEVEL OF EVIDENCE: III

Plasmacytoid Dendritic Cells Promote Immunosuppression in Ovarian Cancer via ICOS Costimulation of Foxp3+ T-Regulatory Cells

Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death among women. Despite its immunogenicity, effective antitumor responses are limited, due, in part, to the presence of forkhead box protein 3-positive (Foxp3(+)) T regulatory (Treg) cells in the tumor microenvironment. However, the mechanisms that regulate the accumulation and the suppressive function of these Foxp3(+) Treg cells are poorly understood. Here, we found that the majority of Foxp3(+) Treg cells accumulating in the tumor microenvironment of EOCs belong to the subset of Foxp3(+) Treg cells expressing inducible costimulator (ICOS). The expansion and the suppressive function of these cells were strictly dependent on ICOS-L costimulation provided by tumor plasmacytoid dendritic cells (pDC). Accordingly, ICOS(+) Foxp3(+) Treg cells were found to localize in close vicinity of tumor pDCs, and their number directly correlated with the numbers of pDCs in the tumors. Furthermore, pDCs and ICOS(+) Foxp3(+) Treg cells were found to be strong predictors for disease progression in patients with ovarian cancer, with ICOS(+) Treg cell subset being a stronger predictor than total Foxp3(+) Treg cells. These findings suggest an essential role for pDCs and ICOS-L in immunosuppression mediated by ICOS(+) Foxp3(+) Treg cells, leading to tumor progression in ovarian cancer.

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.

Phase 1–2 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer

BACKGROUND Biologically targeted therapies have been postulated as a viable strategy to improve outcomes for women with ovarian cancer. We assessed the safety, tolerance, pharmacokinetics, relevant circulating and image-derived biomarkers, and clinical activity of combination aflibercept and docetaxel in this population. METHODS For the phase 1 (pharmacokinetic) study, eligible patients had measurable, recurrent or persistent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with a maximum of two prior chemotherapy regimens. Aflibercept was administered intravenously over three dose levels (2, 4, or 6 mg/kg; one dose every 21 days) to identify the maximum tolerated dose for the phase 2 study. Pharmacokinetics were assessed and dynamic imaging was done during a lead-in phase with single-agent aflibercept (cycle 0) and during combination therapy with intravenous docetaxel (75 mg/m(2)). Eligibility for the phase 2 study was the same as for phase 1. Patients were enrolled in a two-stage design and given aflibercept 6 mg/kg intravenously and docetaxel 75 mg/m(2) intravenously, every 3 weeks. The primary endpoint was objective response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.0. The trial has completed enrolment and all patients are now off study. The trial is registered at ClinicalTrials.gov, number NCT00436501. FINDINGS From the phase 1 study, the recommended phase 2 doses of aflibercept and docetaxel were found to be 6 mg/kg and 75 mg/m(2), respectively. Log-linear pharmacokinetics (for unbound aflibercept) were observed for the three dose levels. No dose-limiting toxicities were noted. 46 evaluable patients were enrolled in the phase 2 trial; 33 were platinum resistant (15 refractory) and 13 were platinum sensitive. The confirmed ORR was 54% (25 of 46; 11 patients had a complete response and 14 had a partial response). Grade 3-4 toxicities observed in more than two patients (5%) were: neutropenia in 37 patients (80%); leucopenia in 25 patients (54%); fatigue in 23 patients (50%); dyspnoea in ten patients (22%); and stomatitis in three patients (7%). Adverse events specifically associated with aflibercept were grade 1-2 hypertension in five patients (11%), and grade 2 proteinuria in one patient (2%). INTERPRETATION Combination aflibercept plus docetaxel can be safely administered at the dose and schedule reported here, and is associated with substantial antitumour activity. These findings suggest that further clinical development of this combination in ovarian cancer is warranted. FUNDING US National Cancer Institute, US Department of Defense, Sanofi-Aventis, Gynecologic Cancer Foundation, Marcus Foundation, and the Commonwealth Foundation.