IntroductionThe learning curve associated with robotic pancreatoduodenectomy (RPD) is a hurdle for new programs to achieve optimal results. Since early analysis, robotic training has recently expanded, and the RPD approach has been refined. The purpose of this study is to examine RPD outcomes for surgeons who implemented a new program after receiving formal RPD training to determine if such training reduces the learning curve.MethodsOutcomes for consecutive patients undergoing RPD at a single tertiary institution were compared to optimal RPD benchmarks from a previously reported learning curve analysis. Two surgical oncologists with formal RPD training performed all operations with one surgeon as bedside assistant and the other at the console.ResultsForty consecutive RPD operations were evaluated. Mean operative time was 354 ± 54 min, and blood loss was 300 ml. Length of stay was 7 days. Three patients (7.5%) underwent conversion to open. Pancreatic fistula affected five patients (12.5%). Operative time was stable over the study and lower than the reported benchmark. These RPD operative outcomes were similar to reported surgeon outcomes after the learning curve.ConclusionThis study suggests formal robotic training facilitates safe and efficient adoption of RPD for new programs, reducing or eliminating the learning curve.

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One in eight women in the United States will develop invasive breast cancer during their lifetime. Of these women, a significant portion (10-16%) will develop metastases to the brain, resulting in significant morbidity and poor prognosis. Symptoms of brain metastasis are devastating and include dizziness, nausea, vertigo, headaches, impaired vision and cognitive functions. Brain metastases arise from highly aggressive triple negative (estrogen, progesterone, and Her2 receptor negative) or Her2 positive (estrogen and progesterone receptor negative, and Her2 positive) mammary tumors and often afflict young, premenopausal women. Less than 2% of women with such lesions survive past 2 years. Since there are currently no effective therapies against brain metastases, the best approach is to prevent their formation by targeting circulating tumor cells before they engraft at distant sites. It has been suggested that cancer stem cells (CSCs) contribute to the metastatic spread in many solid tumors, including those of the breast. A successful preventative agent must kill circulating tumor cells and CSCs before they have a chance to colonize a secondary site while having minimal toxicity against normal tissue. Eburnamonine (EBN) is a pharmacologically active compound derived from the flowering plant Periwinkle with vasoregulatory and anti-hypoxic properties. It has been found to cross the blood-brain-barrier and has been used as a treatment for a number of cerebrovascular disorders, including ischemia and anoxia. EBN has no known neurotoxicity, in fact it has been found to be neuroprotective. A derivative of EBN, 15-methylene-(-)-eburnamonine (15-M-EBN), with increased cytotoxity against cancer cells has been synthesized by our group. We found that EBN is cytotoxic against triple negative human breast cancer cells, MDA-MB-231 (LC50=42.0 μM). Our derivative, 15-M-EBN, is even more effective against triple negative human breast cancer cells, MDA-MB-231 (LC50=14.0 μM), as well as against triple negative breast to brain metastatic cells, MDA-MB-231BR (LC50=26.4 μM); and Her2 positive breast to brain metastatic cells, MDA-MB-231BR-Her2 (LC50=27.2 μM). Mammosphere assay indicated that 15-M-EBN kills CSCs found in MDA-MB-231, triple negative breast cancer cells (LC50=10.3 μM), as well as those found in triple negative breast to brain metastatic cells, MDA-MB-231BR, (LC50=26.2 μM) and Her2 positive breast to brain metastatic cells, MDA-MB-231BR-Her2 (LC50=19.8 μM). Also, by using 3D cultures and coatings of various extracellular matrix component proteins, we established that 15-M-EBN is active under the conditions of environmental-mediated drug-resistance. Staining with Annexin V showed that 15-M-EBN induces apoptosis that we demonstrate to be mediated through the activation of caspases 3, 6, and 7 and cleavage of cytokeratin 18. Addition of reducing agents (N-Acetyl-L-cysteine, glutathione, or DTT) to 15-M-EBN treated cultures blocked its cytotoxic effects, demonstrating that 15-M-EBN acts through the induction of oxidative stress. Furthermore, to establish that the methylene group on the fifteenth carbon in the structure of 15-M-EBN is the reactive site, our group synthesized a compound with a methyl group in place of the methylene (15-methyl-EBN). It was tested in cultures of breast cancer cells and showed that replacing the methylene with the methyl group abrogates the cytotoxic effects of this compound. Taken together our data show that 15-M-EBN kills triple negative and Her2 positive breast cancer cells and CSCs derived from these tumors through an induction of oxidative stress, overcomes the pro-tumorigenic effects of the tumor microenvironment while exhibiting minimal toxicity against normal tissue. These findings suggest that 15-M-EBN has a high potential to become a preventative agent against breast to brain metastases. Citation Format: Mary Minyi Zheng, Britney Harris, James Woods, David Colby, Julia Kirshner. 15-Methylene-Eburnamonine: A preventative agent against breast to brain metastases by targeting circulating tumor cells and cancer stem cells through induction of oxidative stress. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B30.

Background: The safety and feasibility of robotic pancreaticoduodenectomy (RPD) has been demonstrated, resulting in increased utilization due to improved range of instrument articulation, elimination of surgeon tremor, and enhanced three-dimensional visualization. The learning curve associated with RPD, established at 80 cases(1), is a recognized hurdle to implementing a new program. Since the initial learning curve analysis, robotic training has expanded, and the RPD approach has been refined. The purpose of this study is to determine if the required learning curve to optimize proficiency of RPD is reduced for surgeons who received formal RPD training. Methods: The first twenty consecutive patients undergoing RPD at a single tertiary referral institution from October 2018 to July 2019 were analyzed. The only exclusion criteria for attempting a robotic approach was anticipated need for vein resection. Two surgical oncologists with formal training in RPD performed these cases with one serving as the bedside assistant and one at the console. Patient demographics, pathologic characteristics, and 90day post-operative outcomes were collected. Outcomes were compared to optimal RPD benchmarks from a previously reported learning curve analysis(1). Data is reported as mean AE standard deviation or median (range). Results: Mean age was 62 AE 15.8 years, and 65% of patients were female. Mean BMI was 27.7 AE 5.6. Median Charlson Comorbidity Index (CCI) was 3 (range 0-6) with diabetes in 30%, COPD and CAD with MI in 25%, current smoking in 20%, former smoking in 45%, and prior abdominal surgery in 70% of patients. Eight RPDs were performed for pancreatic adenocarcinoma with mean tumor size of 2.6 AE 1.4 cm. One patient underwent conversion related to involvement of the portal vein requiring resection and end-to-end reconstruction. Mean operative time was 375 AE 59 minutes, and median estimated blood loss was 300 ml (range 50-1000 ml). Median length of stay was 7 days (range 5-22), and a median of 23 lymph nodes were harvested (range 7-38). Morbidity occurred in 40% of patients with pancreatic fistula (ISGPF grade B/C) noted in 2 patients (10%). Readmission occurred in 5 patients (25%). Operative time, the best measure of proficiency, was stable during the course of our experience with no significant trends. Conclusion: Following formal training in RPD, operating time, length of stay, and complication rates for RPD were similar to reported optimized outcomes after reaching an established learning curve (Table 1). These results suggest that formal robotic training facilitates safe and efficient adoption of RPD for new programs, reducing the learning curve. Further study of RPD outcomes from surgeons with formal training is required to validate these single institution findings.

Recent published data indicate robotic assisted minimally invasive esophagectomy (RAMIE) can achieve comparable, if not superior outcomes to minimally invasive esophagectomy (MIE). Several studies have demonstrated improved postoperative pain and decreased cardiopulmonary complications following RAMIE for resectable intrathoracic esophageal cancer compared to MIE. Superior three-dimensional visualization and increased instrument precision result in greater lymph node harvest and ensures R0resection without an increase in intraoperative complications or anastomotic leaks. Herein the authors describe their recent adoption of RAMIE as the standard of care over MIE for patients with resectable esophageal cancer. The authors present a detailed approach to preoperative considerations, intraoperative technical nuances and technique and postoperative outcomes and follow-up following RAMIE. An up to date review of the literature is presented and congruently acknowledges RAMIE as a feasible and safe alternative to MIE with comparable oncologic outcomes.