A detailed analysis of the learning curve: robotic hysterectomy and pelvic-aortic lymphadenectomy for endometrial cancer.

OBJECTIVE: To define the learning curve for robotic hysterectomy and pelvic-aortic lymphadenectomy for endometrial carcinoma. METHODS: Patient demographics and segmental operative times on all patients at one institution who underwent robotic comprehensive surgical staging (hysterectomy, pelvic and aortic lymphadenectomy) for endometrial cancer were prospectively collected. Patients were arranged in order based on surgery date and outcomes were compared between quartiles (cases 1-20, 21-40, 41-60, and 61-79). Proficiency was defined as the point at which the slope of the curve becomes less steep for operative times. Efficiency was defined as the point at which the slope is zero. ANOVA or Fisher's exact test was used to compare the procedure times. Locally weighted regression generated smoothed lines that represent operative time over the sequence of the operations. RESULTS: 79 patients were comprehensively staged robotically. While age, the percentage of patients with >/=2 co-morbidities, number of patients with previous laparotomy, EBL, LOS and lymph node counts do not differ between groups, the first 20 patients had a lower BMI compared to the next 20 (27 vs. 34 kg/m(2), P=0.009). Operative times decreased from the first 20 cases to next 20, but was not significantly changed over the next three quartiles. Each component of the procedure has a separate learning curve. CONCLUSIONS: Proficiency for robotic hysterectomy with pelvic-aortic lymphadenectomy for endometrial cancer is achieved after 20 cases; however, the number of procedures to gain efficiency varies for each portion of the case and continues to improve over time.

Robotic hysterectomy and pelvic-aortic lymphadenectomy for endometrial cancer.

OBJECTIVE: To report the learning curve and outcomes after our first 105 patients underwent robotic hysterectomy and pelvic-aortic lymphadenectomy for the comprehensive staging of endometrial cancer. METHODS: We prospectively collected patient demographics, operative times, complications, pathologic results, and length of stay on all patients who underwent robotic hysterectomy pelvic-aortic lymphadenectomy for clinical stage I or occult stage II endometrial carcinoma. RESULTS: One hundred five patients at The Ohio State University between March 2006 and April 2008 underwent exploration with the intent of robotic hysterectomy pelvic-aortic lymphadenectomy. Ninety-two (87.6%) were completed robotically and 13 (12.4%) were converted. The probability of conversion was 15% (95% confidence interval [CI] 8.4-25.7), 24% (95% CI 12.4-39.9), 35% (95% CI 15.9-59.6), and 48% (95% CI 19.1-77.8) for a body mass index of 40, 45, 50, and 55 kg/m(2), respectively. The median body mass index was 34 kg/m(2) (range 19-58). In patients who underwent a robotic hysterectomy pelvic-aortic lymphadenectomy (n=79, 75%) or a robotic hysterectomy-pelvic lymphadenectomy (n=6, 5.7%), the average operating time from skin opening to closure was 242 minutes (+/-50 minutes). The median estimated blood loss was 99 mL (+/-83 mL). The median number of lymph nodes recovered was 29 (range 9-56), 21 (range 5-40) pelvic nodes and 9 (range 2-21) aortic nodes. The median length of stay was 1 night. After analysis of the data, we determined approximately 20 cases are needed to gain proficiency. CONCLUSION: Early experience demonstrates that robotic hysterectomy pelvic-aortic lymphadenectomy for endometrial cancer is feasible, with approximately 20 procedures needed to gain proficiency. LEVEL OF EVIDENCE: III.

Lessons learnt from implementation of a Lynch syndrome screening program for patients with gynaecological malignancy.

Despite a trend towards universal testing, best practice to screen patients presenting with gynaecological malignancy for Lynch syndrome (LS) is uncertain. We report our institutional experience of a co-ordinated gynaecological LS screening program. All patients with endometrial carcinoma or carcinosarcoma, or gynaecological endometrioid or clear cell carcinomas undergo reflex four panel immunohistochemistry (IHC) for MLH1, PMS2, MSH2 and MSH6 followed by cascade somatic hypermethylation analysis of the MLH1 promoter locus for dual MLH1/PMS2 negative tumours. On the basis of these results, genetic counselling and targeted germline mutation testing is then offered to patients considered at high risk of LS. From 1 August 2013 to 31 December 2015, 124 patients were screened (mean age 64.6 years). Thirty-six (29.0%) demonstrated abnormal MMR IHC: 26 (72.2%) showed dual loss of MLH1/PMS2, five (13.9%) dual loss of MSH2/MSH6, three (8.3%) isolated loss of MSH6, and two (5.6%) isolated loss of PMS2. Twenty-five of 26 (96.1%) patients with dual MLH1/PMS2 loss demonstrated MLH1 promoter methylation. Therefore, 11 (8.9%) patients screened were classified as high risk for LS, of whom nine (81.8%) accepted germline mutation testing. Three (2.4% of total screened) were confirmed to have LS, two with germline PMS2 and one with germline MSH2 mutation. Massive parallel sequencing of tumour tissue demonstrated somatic mutations which were concordant with the IHC results in the remainder. Interestingly, the one MLH1/PMS2 IHC negative but not hypermethylated tumour harboured only somatic MLH1 mutations, indicating that universal cascade methylation testing in MLH1/PMS2 IHC negative tumours is very low yield and could be reconsidered in a resource-poor setting. In conclusion, universal screening for LS in patients presenting with gynaecological malignancy using the algorithm described above identified LS in three of 124 (2.4%) of our population. Only three of nine (33.3%) patients considered at high risk for LS by combined IHC and hypermethylation analysis were proven to have LS. Only one of the LS patients was less than 50 years of age and none of these patients would have been identified had more restrictive Amsterdam or Bethesda criteria been applied.

Epithelioid trophoblastic tumour: report of a case in the fallopian tube.

A case of epithelioid trophoblastic tumour (ETT), occurring in a fallopian tube of a 39-year-old woman, is reported. The patient presented with a positive pregnancy test, but continued to have 'periods'. A palpable right adnexal mass was noted that was confirmed on ultrasound. The mass was removed together with the uterus, omentum and associated ovary. Careful examination of the uterus revealed no evidence of either an antecedent tumour or intra-uterine pregnancy. Histologically, the tubal mass displayed sheets and islands of large, relatively uniform, mitotically active polyhedral cells, with surrounding necrosis. The immunoprofile of the tumour was atypical in that alpha-inhibin and epidermal growth factor were weakly positive, but other results were consistent with the diagnosis of ETT. The patient received a foreshortened course of standard EMACO (etoposide, actinomycin-D, methotrexate, vincristine, and cyclophosphamide) combination chemotherapy for high-risk gestational trophoblastic disease. Serum beta-hCG fell from a pre-operative level of 52 000 U/mL to non-pregnant levels within two courses and she remains well and disease-free 12 months post-diagnosis.

Robotic hysterectomy and lymphadenectomy for endometrial cancer: technical aspects and details of success-the Ohio State University method.

Limited data exist regarding description and technical aspects of operating room (OR) set-up, port placement, and instrument selection for robotic gynecologic oncology procedures. The objective of this manuscript and video is to show the established protocol steps at our institution for setting up a robotic hysterectomy and comprehensive lymphadenectomy (dVH-LND) for endometrial cancer. OR preparation of the robotic system prior to patient entry and set-up is demonstrated. The patient is placed in low-lithotomy on an OR table that includes a beanbag and a gel pad that is taped securely for additional stabilization. The arms/shoulders are padded to decrease injury risk and the chest is padded with foam to protect the patient from robotic arm movements. The patient is prepped widely from mid-nipple line to beyond the mid-axillary line and draped. Vaginal instrumentation includes an end-to-end anstomosis (EEA) sizer and pneumo-occluder. Port preferences, placement, and instrument selections are also demonstrated. Using a four-arm robotic system, the camera port is placed midline, approximately 20-27 cm above the pubic symphysis. Robotic ports (RP) for arms #2 and #3 are placed 8-12 cm left lateral to and 15-30° down from the camera port at approximately the level of the umbilicus. A 12 mm laparoscopic assistant port and RP#1 are placed 8-12 cm right lateral to the umbilicus and in the same position as RP#3 and #2, respectively. An additional 5 mm port is placed beneath the costal margin. This method requires only a single docking and one instrument exchange. The bedside assistant stands on the right and is essential for exposure, manipulating the uterus, passage of suture, and troubleshooting potential problems. In addition, port closure technique and methods to remove a large uterus are discussed. We have successfully completed over 70 dVH-LND for endometrial cancer using this protocol. Establishing a systematic routine for OR set-up and port placement in robotic surgery for gynecologic oncology is important for patient safety and allows for efficient use of OR time.

Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer.

OBJECTIVE: To determine the ability of patients to be treated with biweekly bevacizumab and weekly taxane chemotherapy in women with advanced, refractory ovarian cancer. METHODS: Ten patients with advanced, recurrent, and refractory ovarian cancer who were treated with biweekly bevacizumab (10 mg/kg) and weekly taxane (paclitaxel or docetaxel) chemotherapy days 1, 8, 15, and 22 every 28 days were identified retrospectively. All patients were followed with serial CA125 measurements prior to each cycle of therapy; cross-sectional imaging was not used to follow response to therapy. Toxicities were assessed prior to each cycle of treatment. RESULTS: Of the 10 patients treated with weekly taxane and biweekly bevacizumab therapy, all 9 that were evaluable had a decrease in CA125. Five patients have had an increase in CA125 after therapy after a median of three cycles (range 1-4), while 3 patients experienced normalization of CA125 and another with continued improvement in CA125. All symptomatic patients experienced rapid palliation of pain, nausea, and ascites. Side effects have been mild, with no grade 3 or 4 toxicities noted. No treatment delays or discontinuations have been necessary. CONCLUSION: Treatment of advanced, recurrent, refractory epithelial ovarian cancer with bevacizumab and weekly taxane chemotherapy leads to significant, albeit temporary, improvement in the cancer-related symptoms in women treated on this regimen, and short-term exposure to these agents is not associated with significant toxicity. Thus, continued investigation of bevacizumab with weekly scheduling of cytotoxic chemotherapy is imperative.