Early-stage serous fallopian tube carcinoma.

Primary fallopian tube carcinoma (PFTC) is a rare disease. Its location, close association with epithelial ovarian carcinoma, and lack of specific signs and symptoms make diagnosis challenging especially in its early stages. We report a postmenopausal patient who presented with a 2-month history of abdominopelvic pain with watery vaginal discharge. Imaging findings showed a 7 cm complex left adnexal mass. The patient underwent a robotic-assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy and surgical staging. Findings were significant for stage IA serous fallopian tube carcinoma. PFTC is sometimes missed preoperatively and intraoperatively. Available literature review has focused on the clinical and imaging characteristics of PFTC to aid in timely disease diagnosis. Minimally invasive surgery is a viable option in the diagnosis and management of early-stage ovarian cancer due to improved visualisation of pelvic structures, decreased length of hospital stay, decreased estimated blood loss and lower postoperative complication rates compared with laparotomy.

Extended Venous Thromboembolism Prophylaxis after Robotic Staging for Endometrial Cancer.

OBJECTIVES: Our objectives were to estimate the incidence of venous thromboembolism (VTE) after robotic staging for endometrial cancer and to compare the incidence of VTE in patients who received a single dose of preoperative prophylaxis of enoxaparin with those who received extended postoperative prophylaxis. METHODS: This study is a retrospective chart review of patients who underwent robot-assisted surgical staging for endometrial cancer. Patients were categorized into two groups: preoperative prophylaxis (PP), patients who received a single dose of enoxaparin preoperatively, and extended prophylaxis (EP), patients who received 28 days of enoxaparin postoperatively. RESULTS: In total, 148 patients were included, with 117 patients in the PP group and 31 patients in the EP group. The overall incidence of VTE within 30 days postoperatively was 0.67%. No significant difference was found between the PP and the EP groups (0.9% and 0%, respectively; P = 1.00). Most patients in the cohort had endometrioid adenocarcinoma (78%) with low-grade disease (70%), although there were a greater number of patients in the PP group with uterine serous carcinoma compared with the EP group (17% vs 10%; P = 0.034). The PP group had higher estimated blood loss (106 vs 81 mL; P = 0.009) and longer operative times (178 vs 151 min; P = 0.028) compared with the EP group. Significantly more patients in the PP group underwent lymph node dissection compared with the EP group (32% vs 7%; P = 0.008). CONCLUSIONS: The incidence of VTE following robot-assisted surgical staging for endometrial cancer in this study was 0.67%. No significant difference was found in VTE incidence between the PP group compared with the EP group. Mechanical prophylaxis plus a single dose of preoperative pharmacologic prophylaxis may suffice for low-risk patients following robotic surgical staging for endometrial cancer.

Secondary cytoreductive surgery in recurrent clear cell carcinoma of the endometrium: A case report.

INTRODUCTION & IMPORTANCE: Endometrial cancer with high-risk histology is associated with a majority of recurrences and death. However, unlike other cancers, such as ovarian, there is a paucity of research demonstrating the benefits of secondary cytoreduction. In this case report we aim to aid in identifying individuals who may be ideal candidates for secondary cytoreduction surgery after minimally invasive hysterectomy and staging by a gynecologic oncologist at an academic institution and diagnosed with clear cell endometrial cancer. CASE PRESENTATION: A 72 year-old female patient presented with postmenopausal bleeding and was subsequently diagnosed with Stage IIIC2 clear cell carcinoma of the endometrium. She represented 20 months after receiving initial staging and adjuvant chemotherapy with increasing CA-125 levels and radiographic evidence of left para-aortic lymph node oligo metastasis. She underwent secondary cytoreductive surgery via robotic-assisted laparoscopic para-aortic lymph node dissection and salvage chemotherapy. After 45 months of follow-up physical exam, CA-125 levels and CT of the abdomen and pelvis have remained without evidence of disease. CLINICAL DISCUSSION: We review the literature on secondary cytoreductive surgery (SCS) in endometrial cancer (EC) to identify factors associated with improved survival. CONCLUSION: Secondary cytoreduction in endometrial cancer may lead to prolonged progression-free survival in well-selected patients.

Sentinel Lymph Node Sampling in Robot-Assisted Staging of Endometrial Cancer.

OBJECTIVE: Sentinel lymph node (SLN) sampling in endometrial cancer staging has become an acceptable standard. Indocyanine green dye injected into the cervix and detected by near-infrared light is technically simple and sensitive. We aimed to evaluate SLN sampling in robot-assisted surgical staging of endometrial cancer at a university-affiliated teaching hospital. METHODS: A retrospective chart review, from January 2016 to December 2017, of patients who underwent robot-assisted surgical staging with cervical injection of indocyanine green dye detected by near-infrared light. The map rate, sensitivity, false negatives, and negative predictive value were calculated. RESULTS: A total of 105 charts were reviewed; 79 patients met inclusion criteria. The mean age was 65 (range 38-93) and the mean body mass index was 33.3 (range 16-49). Most patients (72.2%) had stage I disease and grade 1 or 2 histology (77.1%). Eight (10.1%) patients had lymph node metastasis. Seventy-two (91.1%) patients had positive mapping to at least 1 SLN. Sixty-two (78.5%) patients had bilateral mapping. Forty-four patients had concurrent pelvic ± para-aortic lymph node dissection and were included in the sensitivity analysis. Five of 44 cases had LN metastasis. The sensitivity was 80%, and the negative predictive value of SLN sampling was 97.5%. CONCLUSIONS: SLN mapping and sampling at a university-affiliated teaching hospital have comparable map rate, sensitivity, and negative predictive value as demonstrated in multiple trials. The technique has the potential to standardize endometrial cancer staging across different practice settings.

Meigs syndrome presenting with severely elevated CA-125 level.

A 64-year-old woman referred to Gynaecological Oncology secondary to the finding of pelvic mass and ascites. Imaging showed multiple pelvic masses, with the largest mass measuring 20 cm in diameter, as well as bilateral pleural effusions and abdominal ascites, suspicious for ovarian carcinoma. Laboratory findings included elevated cancer antigen 125 (CA-125) of 2124 units/mL. The patient underwent an exploratory laparotomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy for pathological evaluation. Postoperatively, the patient had resolution of ascites and pleural effusion. Surgical pathology revealed a 26 cm right ovarian fibroma, confirming the diagnosis of Meigs syndrome. Despite the high suspicion for ovarian carcinoma in patients presenting with elevated CA-125 level, pelvic mass, ascites and pleural effusion, the diagnosis of Meigs syndrome cannot be excluded without pathological evaluation of mass.

Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis.

PURPOSE: Uterine-serous-carcinoma (USC) is an aggressive variant of endometrial cancer. On the basis of preliminary results of a multicenter, randomized phase II trial, trastuzumab (T), a humanized-mAb targeting Her2/Neu, in combination with carboplatin/paclitaxel (C/P), is recognized as an alternative in treating advanced/recurrent HER2/Neu-positive USC. We report the updated survival analysis of NCT01367002. PATIENTS AND METHODS: Eligible patients had stage III to IV or recurrent disease. Participants were randomized 1:1 to receive C/P for six cycles ± T followed by maintenance T until progression or toxicity. Progression-free survival (PFS) was the primary endpoint; overall survival (OS) and toxicity were secondary endpoints. RESULTS: Sixty-one patients were randomized. After a median-follow-up of 25.9 months, 43 progressions and 38 deaths occurred among 58 evaluable patients. Updated median-PFS continued to favor the T-arm, with medians of 8.0 months versus 12.9 months in the control and T-arms (HR = 0.46; 90% CI, 0.28-0.76; P = 0.005). Median-PFS was 9.3 months versus 17.7 months among 41 patients with stage III to IV disease undergoing primary treatment (HR = 0.44; 90% CI, 0.23-0.83; P = 0.015), and 7.0 months versus 9.2 months among 17 patients with recurrent disease (HR = 0.12; 90% CI, 0.03-0.48; P = 0.004). OS was higher in the T compared with the control arm, with medians of 29.6 months versus 24.4 months (HR = 0.58; 90% CI, 0.34-0.99; P = 0.046). The benefit was most notable in those with stage III to IV disease, with survival median not reached in the T-arm versus 24.4 months in the control arm (HR = 0.49; 90% CI, 0.25-0.97; P = 0.041). Toxicity was not different between arms. CONCLUSIONS: Addition of T to C/P increased PFS and OS in women with advanced/recurrent HER2/Neu-positive USC, with the greatest benefit seen for the treatment of stage III to IV disease.

Challenges to Intraoperative Evaluation of Endometrial Cancer.

BACKGROUND AND OBJECTIVES: Intraoperative evaluation of the uterus has been reported to predict risk of lymph node spread in endometrial cancer. Four criteria have been prospectively validated by the Mayo Clinic; histopathology, grade, tumor size, and depth of myometrial invasion. The objective of this study is to assess the accuracy of intraoperative evaluation in a university-affiliated teaching setting. METHODS: This study was a retrospective chart review of 105 cases of endometrial cancer who underwent robotic-assisted staging from January 2016 through December 2017. RESULTS: Seventy-five cases were included. The mean age was 65 y and mean body mass index was 33 kg/m2. Fifty-eight patients (80.6%) had no change between intraoperative and postoperative grade. This yielded a 19.4% discordance rate with a significant disagreement (P = .003, Cohen's κ = 0.705). Fifty-eight patients (82.9%) had no change in depth of invasion. This yielded a 17.1% discordance rate with a significant disagreement (P = .0498, Cohen's kappa of 0.69 [95% confidence interval, 0.53-0.85]). Average tumor diameter was 3.4 cm. Seven patients (11.7%) were upsized from the low-risk (≤2 cm) to the high-risk category (>2 cm). This led to an 11.7% discordance rate, with a significant disagreement (P = .008, Cohen's kappa of 0.69 [95% confidence interval, 0.48-0.89]). In 15 of 75 cases (20%), intraoperative evaluation of the size of the tumor was not possible and deferred to the final pathology report. CONCLUSION: We conclude the Mayo Clinic Criteria cannot be universally adopted until all four criteria can be validated through a prospective study that includes institutions that have variable resources.

Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu.

Purpose Uterine serous carcinoma is a rare, aggressive variant of endometrial cancer. Trastuzumab is a humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2)/neu, a receptor overexpressed in 30% of uterine serous carcinoma. This multicenter, randomized phase II trial compared carboplatin-paclitaxel with and without trastuzumab in patients with advanced or recurrent uterine serous carcinoma who overexpress HER2/neu. Methods Eligible patients had primary stage III or IV or recurrent HER2/neu-positive disease. Participants were randomly assigned to receive carboplatin-paclitaxel (control arm) for six cycles with or without intravenous trastuzumab (experimental arm) until progression or unacceptable toxicity. The primary end point was progression-free survival, which was assessed for differences between treatment arms via one-sided log-rank tests. Results From August 2011 to March 2017, 61 patients were randomly assigned. Forty progression-free survival-related events occurred among 58 evaluable participants. Among all patients, median progression-free survival was 8.0 months (control) versus 12.6 months (experimental; P = .005; hazard ratio [HR], 0.44; 90% CI, 0.26 to 0.76). Similarly, median progression-free survival was 9.3 (control) versus 17.9 (experimental) months among 41 patients with stage III or IV disease undergoing primary treatment ( P = .013; HR, 0.40; 90% CI, 0.20 to 0.80) and 6.0 (control) versus 9.2 months (experimental), respectively, among 17 patients with recurrent disease ( P = .003; HR, 0.14; 90% CI, 0.04 to 0.53). Toxicity was not different between treatment arms, and no unexpected safety signals emerged. Conclusion Addition of trastuzumab to carboplatin-paclitaxel was well tolerated and increased progression-free survival. These encouraging results deserve further investigation to determine their impact on overall survival in patients with advanced or recurrent uterine serous carcinoma who overexpress HER2/neu.

Comparison between 155 cases of robotic vs. 150 cases of open surgical staging for endometrial cancer.

OBJECTIVE: To compare the outcomes of 155 cases of endometrial cancer who had robot-assisted surgical staging to 150 open cases. METHODS: Retrospective chart review of cases of endometrial cancer that underwent staging two different ways by two surgeons at an academic institution. RESULTS: Mean age was 62.4 years in the robotic arm and 65 (P=0.04) in the open arm. Mean body mass index was 34.5 Kg/m(2) in the robotic arm and 33 Kg/m(2) in the open arm (P=0.2). Pelvic and para-aortic lymph node dissection were performed in 94.8% and 67.7% of the robotic cases versus 95.3% and 74% of the open cases, respectively. Mean operative time was 127 min in the robotic arm, and 141 min in the open arm (P=0.0001). Mean lymph node count was 20.3 in the robotic arm, and 20 in the open arm (P=0.567). Mean estimated blood loss was 119 ml in the robotic arm and 185 in the open arm (P=0.015). Mean hospital stay was 1.5 days in the robotic arm, and 4 days in the open arm (P=0.0001). The incidence of postoperative ileus (0.6% vs. 10.7%, P=0.0001), infections (5.2% vs. 24%, P=0.0001), anemia/transfusion (1.3% vs. 7.7%, P=0.005), and cardiopulmonary complications (3.2% vs.14.7%, P=0.003) was significantly lower in the robotic arm vs. the open arm. There was one death in the robotic arm attributed to pre-existing cardiac condition. CONCLUSION: Robotic-assisted staging reaps the benefits of minimally invasive surgery without compromising the adequacy of the procedure. Dedication to the technique shortens the operative time.

Robotic-assisted laparoscopic hysterectomy: outcomes in obese and morbidly obese patients.

OBJECTIVE: To describe patient characteristics and perioperative outcomes among women undergoing roboticassisted laparoscopic hysterectomy and to evaluate the characteristics of nonobese, obese, and morbidly obese patients. METHODS: A retrospective review was conducted of 442 cases of women who underwent robotic-assisted laparoscopic hysterectomy for benign and malignant conditions over a 4-y period at an academic and community teaching hospital. Patient demographics, surgical indications, operative outcomes, and complications were evaluated for patients with a body mass index (BMI) <30 kg/m(2), 30 kg/m(2) to 39.9 kg/m(2), and ≥40 kg/m(2). RESULTS: Of the 442 patients, 257 (58%) were obese or morbidly obese, with a BMI of ≥30 kg/m(2). Overall, the median estimated blood loss was 100 mL (range, 10 to 800), the operative time was 135 min (range, 40 to 436), and the length of stay was 1 d (range, 0 to 22). These did not differ significantly by BMI group. Overall, 11.9% of patients experienced complications (7.9% minor, 4.1% major), and this did not differ significantly across BMI groups. CONCLUSION: Robotic hysterectomy can be performed safely in obese and morbidly obese patients, with surgical outcomes and complications similar to those in nonobese patients.

Vaginal cuff dehiscence in robotic-assisted total hysterectomy.

STUDY OBJECTIVE: The aim of this study was to estimate the cumulative incidence of vaginal cuff dehiscence in robotic-assisted total hysterectomies in our patients and to provide recommendations to decrease the incidence of vaginal cuff dehiscence. METHODS: This was an observational case series, Canadian Task Force Classification II-3 conducted at an academic and community teaching hospital. A total of 654 patients underwent robotic-assisted total laparoscopic hysterectomy for both malignant and benign reasons from September 1, 2006 to March 1, 2011 performed by a single surgeon. The da Vinci Surgical System was used for robotic-assisted total laparoscopic hysterectomy. RESULTS: There were 3 cases of vaginal cuff dehiscence among 654 robotic-assisted total laparoscopic hysterectomies, making our cumulative incidence of vaginal cuff dehiscence 0.4%. The mean time between the procedures and vaginal cuff dehiscence was 44.3 d (6.3 wk). All patients were followed up twice after surgery, at 3 to 4 wk and 12 to 16 wk. CONCLUSION: In our study, the incidence of vaginal cuff dehiscence after robotic-assisted total laparoscopic hysterectomy compares favorably to that of total abdominal and vaginal hysterectomy. Our study suggests that the incidence of vaginal cuff dehiscence is more likely related to the technique of colpotomy and vaginal cuff suturing than to robotic assisted total hysterectomy per se. With proper technique and patient education, our vaginal dehiscence rate has been 0.4%, which is 2.5 to 10 times less than the previously reported vaginal cuff dehiscence rate in the literature.

The significance of perineural invasion in early-stage cervical cancer.

INTRODUCTION: Cervical cancer spreads directly and through lymphatic and vascular channels. Perineural invasion is an alternative method of spread. Several risk factors portend poor prognosis and inform management decisions regarding adjuvant therapy. OBJECTIVE: To evaluate the incidence and significance of PNI in early cervical cancer. METHODS: Retrospective chart review of early-stage cervical cancer patients (IA-IIA) from 1994 to 2009. RESULTS: One hundred ninety two patients were included, 24 with perineural invasion in the cervical stroma (cases) and 168 without (controls). The mean age of the cases was 53 years, versus 45.9 in the controls (P=0.01). PNI was associated with more adjuvant therapy (P=0.0001), a higher stage (P=0.005), a larger tumor size (≥ 4 cm) (P<0.0001), lymphovascular space invasion (P=0.002), parametrial invasion (P<0.0001) and more tumor extension to the uterus (P=0.015). On multivariate analysis using an adjusted hazard ratio, risk factors for recurrence included grade (HR, 95% CI; 3.61, 1.38-9.41) and histopathology (HR, 95% CI; 2.85, 100-8.09). Similarly, risk factors for death included grade (HR, 95% CI; 3.43, 1.24-9.49) and histopathology (HR, 95% CI; 3.71, 1.03-13.33). Perineural invasion was not identified as an independent risk factor for either recurrence or death. The mean follow up time was 56 months. There was no significant difference in recurrence (P=0.601) or over-all survival (P=0.529) between cases and controls. CONCLUSION: While perineural invasion was found to be associated with multiple high-risk factors, it was not found to be associated with a worse prognosis in early cervical cancer.

erbB2 Overexpression in Uterine Serous Cancer: A Molecular Target for Trastuzumab Therapy.

Endometrial cancer is the most common female genital tract malignancy in the United States. Type I endometrial cancer is usually diagnosed at an early stage, and has a good prognosis. Type II is very aggressive, and is responsible for most uterine cancer relapses and deaths. Uterine serous adenocarcinomas (USC) constitute the majority of Type II variants. They have a higher propensity for lymph node and distant metastases. They are frequently aneuploid and associated with p53 mutations. erbB2 overexpression in USC has been described. The incidence, which is higher in African Americans, ranges from 18-80%. erbB2 overexpression was found to be associated with higher stage, chemoresistance, and worse survival. Trastuzumab a humanized mAb was approved by the FDA for treatment of breast cancers that overexpress erbB2 in combination with standard chemotherapy. Evidence of trastuzumab activity in USC has been reported in vitro, as well as in case reports of advanced and recurrent cases. Promising results were obtained in these heavily pretreated patients either with trastuzumab alone or in combination with chemotherapy. This supports the hypothesis that trastuzumab may very well be an attractive and viable treatment option for advanced stage USC tumors that overexpress the erbB2, and is worthy of further study.