A prospective randomized trial of intravenous ketorolac vs. acetaminophen administered with opioid patient-controlled analgesia in gynecologic surgery.

OBJECTIVE: To determine which non-narcotic analgesic, acetaminophen (Ofirmev®) or ketorolac (Toradol®), provides better post-operative pain control when combined with an opioid patient-controlled analgesia (PCA) pump. Secondary objectives include comparisons of the rates of ileus, post-operative bleeding, transfusions, and length-of-hospitalization (LOH). METHODS: A prospective, randomized trial of acetaminophen (A) 1-g intravenous (IV) every 6-h or ketorolac (K) 15-mg IV every 6-h from post-operative day 1-3 in addition to an opioid PCA for patients undergoing benign or malignant gynecologic laparotomy procedures was performed. Abstracted data included pain levels via visual analogue pain scales (VAS), amount of narcotic used, hepatic enzyme levels, hemoglobin, urine output, blood transfusions, time to return of flatus and LOH. RESULTS: One-hundred patients were accrued and underwent 55 benign gynecologic laparotomies and 45 cancer-related laparotomies. VAS pain levels (3.3 K, 3.5 A) and morphine PCA use (79.1 oral morphine equivalents [OME] K vs. 84.5 A) were not different, however dilaudid PCA usage was less by K patients (84.4 OME K and 136.8 OME A, p < 0.001). There was a significant hemoglobin change between the two groups (2.6 g K vs. 2 g A, p = 0.015), however blood transfusions were equal (28% K, 22% A, p > 0.05). Return of flatus was 2.7-days for K vs. 3.4-days for A (p = 0.011) and LOH was not different (4.4-days K vs. 5.1-days A, p = 0.094). CONCLUSIONS: Both intravenous ketorolac and acetaminophen provide similar post-operative analgesia through VAS pain scales and total usage of morphine via PCA pumps. Use of ketorolac with dilaudid PCA was associated with less dependence on dilaudid and a quicker return of bowel function than acetaminophen, however length of stay and transfusion rates were not different.

A Prospective Cohort Study Comparing Colorimetric and Fluorescent Imaging for Sentinel Lymph Node Mapping in Endometrial Cancer.

BACKGROUND: This prospective cohort study aimed to assess sentinel lymph node (SLN) mapping using isosulfan blue (ISB) compared with ISB plus indocyanine green (ICG) and near-infrared imaging (NIR) for patients with endometrial cancer. METHODS: In this study, 200 patients with endometrial cancer underwent SLN assessments and were randomized to ISB + ICG (n = 180) or ISB alone (n = 20). Blue dye determinations were recorded for all 200 cases followed by NIR imaging of ICG for 180 randomized subjects. All the patients underwent robotically assisted hysterectomy with pelvic ± aortic lymphadenectomy. RESULTS: The mean age of the patients was 64.5 ± 8.4 years, and the mean body mass index (BMI) was 33 ± 7.6 kg/m2. The histologies were endometrioid G1 (43%), G2 (30%), G3 (7%), and type 2 (20%). The mean time from dye injection to initiation of mapping was 13.4 ± 6.2 min, and the time to removal of SLN was 17.4 ± 11.2 min. Detection of SLN for the 20 ISB control cases did not differ from that for the 180 ISB + ICG cases (p > 0.05). The rates of SLN detection for ISB + ICG/NIR (n = 180) versus ISB (n = 200) were as follows: bilateral (83.9 vs. 40%), unilateral (12.2 vs. 36%), and none (3.9 vs. 24%) (p < 0.001). The median SLN per case was 2 (range 0-4). Positive SLNs were found in 21.1% (n = 38) of the ISB + ICG cases compared with 13.5% (n = 27) of the ISB cases (p = 0.056). The false-negative rate for SLN biopsy was 2.5% (95% confidence interval, 0.1-14.7%). In 61% (25/41) of the node-positive cases, SLN was the only positive lymph node (LN). Isolated tumor cells were found in 39.5% (15/38) of the SLN metastasis cases compared with 26.7% (4/15) of the non-SLN metastasis cases (p = 0.528). CONCLUSIONS: In this prospective study, ISB + ICG and NIR detected more SLNs and more LN metastases than ISB alone. Assessment of SLN with ICG + ISB/NIR imaging had excellent sensitivity for detection of metastasis and no safety issues.

Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis.

OBJECTIVES: To compare the performance of sentinel lymph node (SLN) mapping with staging lymphadenectomy versus staging lymphadenectomy alone for the detection of metastasis and the use of adjuvant therapies in patients with endometrial cancer. METHODS: All patients with apparent early-stage endometrial cancer (n=780) who underwent robotic-assisted hysterectomy with pelvic±aortic lymphadenectomy from July-2006 to June-2013 were compared [pelvic±aortic lymphadenectomy (n=661) versus SLN-mapped cases with pelvic±aortic lymphadenectomy (n=119)]. Isosulfan-blue and indocyanine-green with near-infrared imaging were used for SLN mapping. Clinico-pathological data, FIGO stage, GOG risk category, and adjuvant therapies were compared. RESULTS: Non-mapped and mapped cases were comparable with respect to BMI, histology, depth-of-invasion, and lympho-vascular space invasion. The mapped group had more pelvic lymph node (LN) harvested compared to non-mapped group (26.4±10.5 vs. 18.8±8.5, p<0.001). Aortic LN yields were identical for both groups (9.0±5.6 vs. 9.0±6.0). The mapped group had more LN metastasis detected (30.3% vs. 14.7%, p<0.001), more stage IIIC (30.2% vs. 14.5%, p<0.001), more GOG high-risk cases (32.8% vs. 21.8%, p=0.013), and received more chemotherapy+radiation (28.6% vs. 16.3%, p<0.003). The SLN was the only metastasis in 18 (50%) mapped cases with positive nodes. The SLN false negative rate was 1/36 (2.8%). Micrometastases or isolated tumor cells were identified in 22/35 (62.9%) SLN metastases. Multivariate analysis demonstrated that SLN mapping imparted a significant effect on the detection of metastatic disease [adjusted OR=3.29, p<0.001]. CONCLUSIONS: The performance of SLN mapping with staging lymphadenectomy increased the detection of lymph node metastasis and was associated with more use of adjuvant therapies.

Analysis of disease recurrence and survival for women with uterine malignancies undergoing robotic surgery.

OBJECTIVES: To evaluate recurrence-free survival (RFS) and overall survival (OS) for patients who underwent robotic-assisted laparoscopic hysterectomy (RALH) for uterine malignancies. METHODS: Medical records from 372 patients with uterine malignancies who underwent RALH from 3/06 to 3/09 at two institutions were reviewed for clinico-pathologic data, adjuvant therapies, disease recurrence, and survival. Median follow-up for survival analysis was 31 ± 14 months. Thirty (8.1%) patients were lost to follow-up before 12 months and censored from the recurrence analysis. RESULTS: Mean age and BMI of 372 patients was 61.8 ± 9.8 years and 32.2 ± 8.4 kg/m(2) (range 19-70). Robotic procedures included RALH 16 (4.3%), RALH with pelvic lymphadenectomy (PL) 96 (25.8%), and RALH with pelvic-and-aortic lymphadenectomy (PAL) 252 (67.7%) cases. Histology included 319 (85.8%) endometrioid and 53 (12.6%) high-risk histologies. Mean pelvic and aortic lymph node counts were 16.8 ± 8.7 and 8.4 ± 4.5, respectively. Lymph node metastases were identified in 26 (7.3%) cases. Adjuvant therapies were prescribed for 108 (29.1%) of patients: 7.8% brachytherapy, 1.9% pelvic radiation+brachytherapy, 7.8% chemotherapy, 11.6% chemotherapy+radiation. Risk of recurrence for all patients was 8.3% and 17 (4.6%) patients died of disease. The estimated 3-year recurrence-free survival (RFS) for the entire study group was 89.3% and the estimated 5-year overall survival (OS) was 89.1%, compared to 92.5% and 93.4% for the endometrioid sub-set. CONCLUSIONS: Patients with endometrial cancer undergoing robotic hysterectomy with staging lymphadenectomies during our 3-years of robotic experience had low-risk for recurrence and excellent disease-specific survival at a median follow-up time of 31 months.

Short- and long-term morbidity and outcomes after robotic surgery for comprehensive endometrial cancer staging.

OBJECTIVE: Although intra-operative and immediate postoperative complications of robotic surgery are relatively low, little is known about long-term morbidity. We set out to assess both short- and long-term morbidities after robotic surgery for endometrial cancer staging. METHODS: All patients who underwent robotic staging for EMCA between 2006 and 2009 from two institutions were identified. Patient charts were retrospectively reviewed for surgical complications and postoperative morbidities. RESULTS: Five hundred three patients were identified. No differences in complication rates were found between 2006-2007 and 2008-2009, even though the median BMI increased from 29.9 (range 19-52) to 32 (range 17-70) (p=0.03). 6.4% of cases were converted to laparotomy. Median length of stay was one day (range 1-46). No cystotomies, two enterotomies, one ureteric injury, and five vessel injuries occurred (1.6% intra-operative complications). Thirty-eight (7.6%) patients developed major postoperative complications, 11 (2.2%) had wound infections, and 15 (3%) required a transfusion in the 30-day peri-operative period. The total venous thromboembolism (VTE) rate for robotic cases was 1.7%. Partial cuff dehiscence managed conservatively occurred in 5 (1%) and complete dehiscence requiring closure in 7 (1.4%) patients; Sixty-three (13.4%) patients who had robotic staging developed lymphedema, with 40 (8%) requiring physical therapy. CONCLUSIONS: This study provides one of the largest cohorts of patients with robotic-assisted hysterectomy and lymphadenectomy (in 92.6%) with an assessment of morbidity. Our data demonstrates that robotic surgical staging can be safely performed with a low risk of short-term complications and lymphedema is the most frequent long-term morbidity.

Peri-operative outcomes of patients with stage IV endometriosis undergoing robotic-assisted laparoscopic surgery.

We analyzed peri-operative outcomes of 80 patients who underwent robotic-assisted laparoscopic surgery and were diagnosed with stage IV endometriosis (revised American Society for Reproductive Medicine) between January 2007 and December 2010 at a tertiary gynecologic oncology referral center with a fellowship training program. Eligible women had a combination of one or more factors: pelvic mass, sub-acute or chronic pelvic pain, dysmenorrhea, dyspareunia, elevated serum CA-125, diagnosed with stage IV endometriosis at surgery with robotic-assisted gynecologic procedures using the da Vinci(®) Surgical System. The mean age was 43.7 ± 7.0 years, body mass index 27.5 ± 7.4 kg/m(2), and 23 (28.9%) patients had prior endometriosis surgery. Presenting symptoms included: chronic pelvic pain (48.8%), dysmenorrhea (40.3%), and dyspareunia (33.8%). Sixty-nine (86%) patients had pelvic masses (43 unilateral and 26 bilateral). Thirty-seven (46.3%) had elevated CA-125 levels (mean 97.9 ± 71.6 U/ml). Forty-eight (60%) underwent robotic-assisted laparoscopic hysterectomy (RALH)/bilateral salpingo-oophorectomy (BSO), 9 (11.3%) RALH/unilateral salpingo-oophorectomy (USO), 5 (6.3%) modified radical hysterectomy, and 10 (13%) USO or BSO only. Four (5%) had ovarian cystectomies with excision of endometriotic implants. Three (3.8%) underwent appendectomy and no patient required bowel resection. Four (5%) patients required conversion to laparotomy during the first 15 cases of this series [dense adhesions (3) and ureteral injury (1)]. Mean operative time was 115 ± 46 min, blood loss 88 ± 67 ml, and length of stay 1.0 ± 0.4 days. There were four (5%) complications (ureteral injury, cuff abscess, cuff hematoma, re-admission for nausea and vomiting secondary to narcotics) and no transfusions. One (1.3%) patient underwent a second surgery for pain (dyspareunia). Robotic-assisted surgery for stage IV endometriosis resulted in excellent pain relief, with few laparotomy conversions or complications during a robotic learning-curve experience.

Robotic-assisted laparoscopic hysterectomy and lymphadenectomy for endometrial cancer: Analysis of surgical performance.

OBJECTIVES: To provide an objective analysis of surgical performance of robotic-assisted laparoscopic hysterectomy (RALH) with lymphadenectomy for endometrial cancer during the learning phase of the procedure and to assess opportunities for improvement. METHODS: From July 2006 to March 2008, 100 patients with endometrial cancer underwent RALH with lymphadenectomy using the da Vinci Robotic Surgical System. Data were analyzed for operative time (OT), estimated blood loss (EBL), length of stay (LOS), intra-operative complications, surgical-pathologic factors, and post-operative complications using an intent-to-treat analysis. A comparison of the data on a quartile (Q) basis was performed for the 100 RALH cases and separately for the 65 cases that had a complete pelvic-and-aortic lymphadenectomy (PAL). RESULTS: Age and body mass index (BMI) did not change significantly during the study. More grade 3 tumors were treated in the last 50 cases (22% vs. 10%, p<0.05). Stage III tumors were identified in 18.7% cases in Q2-4 and none in Q1 (p<0.05). The number of patients undergoing complete PAL and the number of aortic lymph nodes (LN) removed per case increased each quarter. There were 4 (4%) conversions to laparotomy. Delayed vaginal cuff healing decreased from 16% in Q1 to 0% in Q3-4. No case required blood transfusion. Comparing first 10 cases to the last 10 cases, the total LN counts increased from 15 to 21 nodes, the aortic LN counts increased from 4.7 to 8.0, and the OT decreased from 203 to 160 min. Intra-surgeon analysis revealed an improvement in the total LN yields from first 50 to second 50 cases for each surgeon. CONCLUSIONS: Operative times decreased and aortic dissections improved with increasing LN counts during the first 100 cases of RALH. Furthermore, patient safety and improvement in surgical performance was demonstrated.

Robotically assisted laparoscopic hysterectomy versus total abdominal hysterectomy and lymphadenectomy for endometrial cancer.

OBJECTIVE: To compare surgical morbidity and clinical-pathologic factors for patients with endometrial cancer (EC) undergoing robotic-assisted laparoscopic hysterectomy (RALH) versus total abdominal hysterectomy (TAH) with aortic and/or pelvic lymphadenectomy (LA). METHODS: During the first 14 months of a robotics surgical program, 56 patients with EC were scheduled to undergo RALH with LA. Cases were analyzed for operative (op) time, estimated blood loss (EBL), transfusion, intra- and post-op complications, surgical-pathologic data, patient demographics and length of stay (LOS). Data was compared to 106 serially treated patients with EC who underwent TAH with LA immediately prior to initiation of our robotics program. RESULTS: Three robotic cases (5.4%) were converted to TAH secondary to intra-op factors. FIGO stages for RALH vs. TAH were: stage I (82 vs. 69%), stage II (7 vs. 7.5%) and stage III (11 vs. 21.5%). Patients' mean age was 59+/-10 vs. 63+/-11 years (p=0.05) and body mass index (BMI) was 29+/-6.5 vs. 34+/-9 kg/m(2) (p=0.0001) for the robotic and open groups, respectively. Severe medical co-morbidities affected 5.4% of robotic patients compared to 8.5% of open cases (p>0.05). Comparing RALH and TAH, mean op time was 177+/-55 vs.79+/-17 min (p=0.0001), EBL was 105+/-77 vs. 241+/-115 ml (p<0.0001), transfusion was 0 vs. 8.5% (p=0.005), and LOS was 1.0+/-0.5 vs. 3.2+/-1.0 days (p<0.0001). Robotic patients incurred a 3.6% major peri-operative complication rate while women undergoing open procedures had an incidence of 20.8% (p=0.007). Total lymph node count was 19+/-13 nodes for robotic cases vs. 18+/-10 nodes obtained from open hysterectomy patients. CONCLUSIONS: Patients with EC who underwent RALH with LA during the first year of our robotics program were younger, thinner and had less cardio-pulmonary illness than patients previously treated with TAH and LA. LOS, EBL and peri-op complication rates were significantly lower for the robotic cohort.

Clinical-pathologic and morbidity analyses of Types 2 and 3 abdominal radical hysterectomy for cervical cancer.

OBJECTIVE: To provide representative data analyses of surgical morbidity and clinical-pathologic factors for Types 2 and 3 abdominal radical hysterectomies (ARH) with pelvic+/-aortic node dissection performed in a private practice with a fellowship-training program. METHODS: From 1997 to 2005, 329 cervical cancer patients underwent ARH with lymphadenectomy. Two hundred and one cases performed at our primary institution were analyzed for operative time, blood loss, intra-operative complications, surgical-pathologic data, recurrence of disease and adjuvant therapy. RESULTS: We evaluated 201 surgical patients who underwent Type 2 (n=45) or Type 3 (n=156) ARH with node dissection. The FIGO stages were: IB1=64%, IB2=6.5%, IA=28.4%, and IIA=1%. Aortic node dissection was performed in 64% of Type 3 cases and none of Type 2 cases. Pfannenstiel incision was used in 80% (Type 2) and 76% (Type 3) cases. A suprapubic catheter was placed in 9% of Type 2 and 81% of Type 3 cases. Median age and weight were 47+/-13 years and 149+/-35 lb. Positive nodes were identified in 12% of Type 3 and 2.2% of Type 2 cases. No positive aortic nodes were found. For Types 2 and 3 ARH, median operative time was 80+/-19 vs. 99+/-23 min (p<0.001) and blood loss was 250+/-134 vs. 300+/-234 ml (p<0.001). The transfusion rate was 3%. Intra-operative complications included: 3 ureteral injuries and 1 colotomy. Tumor histology was 60% squamous, 37% adenocarcinoma, 1% adenosquamous, and 2% others. CONCLUSIONS: ARH with pelvic lymphadenectomy in modern practice is an efficient, safe procedure with low transfusion rate and shorter hospital stay than previously reported. Data will be useful as comparison when scrutinizing novel approaches to radical hysterectomy including robotic-assisted and laparoscopic techniques.

Alpha-fetoprotein-producing serous carcinoma of the uterus metastasizing to the ovaries, mimicking primary ovarian yolk sac tumor: a case report and review of the literature.

In the uterus, most alpha-fetoprotein (AFP) producing neoplasms belong to the categories of malignant mixed muellerian tumor, hepatoid carcinoma, and yolk sac tumor. We describe the case of a 44-year-old woman who presented with vaginal bleeding, pelvic mass, and preoperative elevated AFP serum level, clinically suggestive of a primary ovarian yolk sac tumor. However, histological examination revealed a uterine AFP-producing papillary serous carcinoma, which has metastasized to the ovaries. Upon review of the literature on primary endometrial neoplasms with AFP production, 2 categories with possibly different histogenesis and biological behavior become evident: the primary yolk sac tumor of the uterus in young patients (range, 24-49 years; mean, 34 years) and the common high grade endometrial carcinoma with yolk sac dedifferentiation or aberrant AFP production in elderly patients (range, 55-69 years; mean, 63.7 years). In addition to being only the second case of uterine AFP-producing papillary serous carcinoma, this case is unusual for its clinical and radiological presentation as well as the relatively young age of the patient.

Endometroid adenocarcinoma of the uterus with cardiac metastasis. A case report and six-year follow-up.

BACKGROUND: There are few reported cases of cardiac metastasis associated with endometrial cancer (EC) and no reports of long-term survival. We report a case of EC presenting with metastasis to the right ventricle resulting in right heart failure. CASE: A 61-year-old woman presented with a 10-day history of increasing pedal edema. Two-dimensional echocardiography (2DE) revealed a large echogenic mass within the right ventricle. She underwent exploration of the heart with debulking which revealed a metastatic poorly differentiated epithelial tumor. Further work-up with a dilation and curettage revealed a poorly differentiated EC. A total abdominal hysterectomy with pelvic and para-aortic lymhadenectomy was performed with disease confined to the uterus/cervix. She then received cardiac radiation with concurrent cisplatin, followed by pegylated liposomal doxorubicin (PLD) for 1 year and remained disease free through 6.5 years of follow-up. At 6.8 years, she died of a constrictive pericarditis with no evidence of disease. CONCLUSION: While experience with cardiac metastasis for gynecologic malignancy is limited, it appears that multimodality therapy affected a durable complete response however late complications of cardiac radiation ultimately lead to death.