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Ampullary neuroendocrine tumors (NETs) make up

Ampullary neuroendocrine tumors (NETs) make up 1% of all gastroenteropancreatic NETs, and information is limited to case series. This study compares patients with ampullary, duodenal, and pancreatic head NETs.The National Cancer Database (2004-2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Survival was evaluated using Kaplan-Meier analysis and Cox regression.Overall, 872, 9692, and 6561 patients were identified with ampullary, duodenal, and pancreatic head NETs, respectively. Patients with ampullary NETs had more grade 3 tumors (n = 149, 17%) than patients with duodenal (n = 197, 2%) or pancreatic head (n = 740, 11%) NETs. Patients with ampullary NETs had more positive lymph nodes (n = 297, 34%) than patients with duodenal (n = 950, 10%) or pancreatic head (n = 1513, 23%) NETs. On multivariable analysis for patients with ampullary NETs, age (hazard ratio [HR] 1.03, p 0.0001), Charlson-Deyo score of 2 (HR 2.3, p = 0.001) or ≥3 (HR 2.9, p = 0.013), grade 2 (HR 1.9, p = 0.007) or grade 3 tumors (HR 4.0, p 0.0001), and metastatic disease (HR 2.0, p = 0.001) were associated with decreased survival. At 5 years, the overall survival (OS) for patients with ampullary, duodenal, and pancreatic head NETs was 59%, 71%, and 50%, respectively (p 0.0001), whereas the 5-year OS for patients with ampullary, duodenal, and pancreatic head NETs who underwent surgery was 62%, 78%, and 76%, respectively (p 0.0001).Ampullary NETs were more likely to present with high-grade tumors and lymph node metastases. Based on the clinicopathologic and survival data, ampullary NETs have a unique underlying biology compared with duodenal and pancreatic head NETs.

Ampullary neuroendocrine tumors (NETs) make up

EZH2 is crucial for the progression of prostate cancer (PCa) and castration-resistant prostate cancer (CRPC) through upregulation and activation of progenitor genes, as well as androgen receptor (AR)-target genes. However, the mechanisms by which EZH2 is regulated in PCa and CRPC remain elusive. Here we report that EZH2 is post-transcriptionally regulated by SKP2 in vitro in cultured cells and in vivo in mouse models. We observed aberrant upregulation of Skp2, Ezh2 and histone H3 lysine 27 trimethylation (H3K27me3) in both Pten null mouse embryonic fibroblasts (MEFs) and Pten null mouse prostate tissues. Loss of Skp2 resulted in a striking decrease of Ezh2 levels in Pten/Trp53 double-null MEFs and in prostate tumors of Pten/Trp53 double-null mutant mice. SKP2 knockdown decreased EZH2 levels in human PCa cells through upregulation of TRAF6-mediated and lysine(K) 63-linked ubiquitination of EZH2 for degradation. Ectopic expression of TRAF6 promoted the K63-linked ubiquitination of EZH2 to decrease EZH2 and H3K27me3 levels in PCa cells. In contrast, TRAF6 knockdown resulted in a reduced EZH2 ubiquitination with an increase of EZH2 and H3K27me3 levels in PCa cells. Furthermore, the catalytically dead mutant TRAF6 C70A abolished the TRAF6-mediated polyubiquitination of recombinant human EZH2 in vitro. Most importantly, a concurrent elevation of Skp2 and Ezh2 was found in CRPC tumors of Pten/Trp53 mutant mice, and expression levels of SKP2 and EZH2 were positively correlated in human PCa specimens. Taken together, our findings revealed a novel mechanism on EZH2 ubiquitination and an important signaling network of SKP2-TRAF6-EZH2/H3K27me3, and targeting SKP2-EZH2 pathway may be a promising therapeutic strategy for CRPC treatment.

ARF couples with TP53 in a canonical signaling pathway to activate cellular senescence for tumor suppressive function under oncogenic insults. However, the mechanisms on aberrant elevation of ARF in cancers are still poorly understood. We previously showed that ARF (p14ARF in human and p19Arf in mouse) elevation correlates with PTEN loss and stabilizes SLUG to reduce cell adhesion in prostate cancer (PCa). Here we report that ARF is essential for MMP7 expression, E-Cadherin decrease and the anchorage loss to the extracellular matrix (ECM) in PCa in vitro and in vivo. We found that Mmp7 is aberrantly elevated in cytosol and nucleus of malignant prostate tumors of Pten/Trp53 mutant mice. Interestingly, p19Arf deficiency strikingly decreases Mmp7 levels but increases E-Cadherin in Pten/Trp53/p19Arf mice. ARF knockdown markedly reduces MMP7 in human PCa cells. Conversely, tetracycline-inducible expression of ARF increases MMP7 with a decrease of E-Cadherin in PCa cells. Importantly, MMP7 physically binds ARF to show the co-localization in nucleus. Co-expression of MMP7 and ARF promotes cell migration, and MMP7 knockdown decreases wound healing in PCa cells. Furthermore, MMP7 elevation correlates with ARF expression in advanced human PCa. Our findings reveal for the first time that the crosstalk between ARF and MMP7 in nucleus contributes to ECM network in tumor microenvironments in vivo, implicating a novel therapeutic target for advanced PCa treatment.

4628 Background: ESPAC-4 study showed that GemCap conferred a survival benefit over gemcitabine monotherapy in resected PC patients. ESPAC-4 included patients with median age of 65 years (37-81) and ECOG performance status (PS) of 0 (43%), 1 (54%) and 2 (2%) who received a median cumulative dose of gemcitabine of 15,000 mg/m2, capecitabine. Here we present our experience with an adopted biweekly regimen of GemCap in patients who were ≥ 75 years and those who were deemed not suitable for ESPAC-4 regimen. Methods: Patients ≥ 75 years with resected PC, ECOG PS of 0-2 and no prior treatments were included. Patients were treated with a modified regimen of gemcitabine (1000-2000 mg/m2) every 2 weeks and capecitabine (800-1000 mg/m2) day 1-7 every 2 weeks. Patients were evaluated for progression-free survival (PFS), overall survival (OS) and sites of recurrence. Toxicities were graded according to NCI CTCAE v5.0. Results: Thirty-five (22M, 13F) patients, ≥ 75 (median age 79) treated with biweekly Gem-Cap adjuvant treatment. 7 (28%) patients had ECOG PS of 1 and 28 (72%) had ECOG PS of 2. There were 5, 7 and 16 patients with stage I, II and III disease. Nine patients (25%) had R1 and 26 (75%) had R0 resection. The median PFS and OS were 8.0 months and 22.0 months. Nine (25%) had local recurrence, 21 (60%) had metastatic disease and 3 (8.6%) had NED. Two patients were lost to follow-up. The most frequent toxicities were grades 1-2 anemia (20%), thrombocytopenia (8%) and hand-foot syndrome (HFS) (10%). Grade ≥3 included diarrhea (4%) and HFS (1%) with no treatment-related discontinuations. Treatment compliance was 100%. Delays were necessary in 7% of cases and dose reduction was required in 4% of cases. There was no treatment related death. Conclusions: This schedule of biweekly GemCap regimen suggests an acceptable option in for elderly, frail patients with PC and warrants further exploration in patients not suitable for FOLFIRINOX, full dose GemCap or a clinical trial. This regimen required fewer dose reduction, omission or delays and allowed to administer pegylated-filgrastim. Previous studies have also shown decreased toxicity and equal efficacy of 7/7 schedule of capecitabine. Moreover, fewer visits to oncology and related expense do favor towards benefit. Additionally, this tolerable regimen is ideal to be combined with immunotherapy in clinical trials for this patient population.

Aneurysmal degeneration of the visceral branches of the abdominal aorta is a rare and potentially life-threatening disease entity. Visceral artery aneurysms (VAAs) are exceedingly rare and have a prevalence of 0.1 to 2%. The left gastric artery aneurysm (LGAA) is even more rare and accounts for less than 4% of all VAAs. There is scarce literature on treatment of LGAA by embolization; however, to date successful laparoscopic repair of an LGAA has not been described. We describe the successful treatment of an LGAA by laparoscopic ligation and resection in a 68-year-old male patient.

Background The early removal of central intravenous (IV) catheters, as a means of reducing the incidence of central line–associated blood stream infections (CLABSI), remains a major health care initiative. However, attaining IV access in the surgical intensive care unit (SICU) can be quite difficult. We report the success of a novel, resident-driven program for the placement of ultrasound-guided midline catheters in critically ill patients. Materials and methods A prospective pilot study of 31 subjects admitted to the SICU from June to December 2011 was performed. Intermediate-length (20 cm) midline catheters were placed by trained housestaff, under ultrasound guidance, into the basilic or cephalic veins. Procedural details including time to cannulation, complications, and costs were recorded. Results Successful placement was achieved in 96.8% (n = 30), with a mean follow-up of 9.8 ± 5.6 (range 2–21) days. An average of 1.3 ± 0.7 (range 1–4) attempts with a median of 13.0 ± 14.5 (range 0.5–68) minutes was required for successful venous cannulation. The most common site was the basilic vein (n = 23). Only minor complications were encountered; three catheters leaked at the insertion site and one patient developed phlebitis. No CLABSI occurred. The total procedure cost was $87 per catheter for the SICU team compared with $1500 per catheter when performed by an interventional radiologist. During the study period, a total of 283 central line days were avoided with an estimated cost savings of $13,614. Conclusions Ultrasound-guided midline catheters placed by the housestaff are a cost-effective alternative for patients in the SICU with difficult IV access. Successful placement can help facilitate early central line removal and thus may reduce CLABSI rates.

Background. Parenteral route is accepted for delivering nutrition when enteral feeding is not possible. Standardized premixed parenteral nutrition solution (SPNS) formulations are uniform in their characteristics and can be chosen based on the same nutrient calculations. We compared the feasibility of administering SPNS as an alternative to customized parenteral nutrition solution (CPNS) and calculate its cost implications. Methods. Retrospective review of 47 patients receiving CPNS at a tertiary care hospital ICU was performed and compared with SPNS formulations. The amounts of macro- and micronutrients (days 1, 3, 5, 7) were recorded and averaged to 2000-mL bag. These data were compared with the available premixed formulations and percentage differences were calculated. The costs and manpower for CPNS were obtained from our institutional central pharmacy. Results. The percentage difference for carbohydrates and proteins ranged from −1.0% to 2.9% and 5.8% to 9.0% with an average of 0.8% and 7.0%, respectively across all days. Since premixed micronutrients were only available in one formula, they were not easily comparable. The cost analysis showed an average savings of approximately $130 per parenteral nutrition bag. Conclusions. While macronutrients are quite comparable between formulations, any required micronutrients should be managed individually. SPNS has potential cost savings compared with CPNS when applied in the right setting.

An ectopic pancreas is defined as pancreatic tissue lacking vascular or anatomic communication with the normal body of the pancreas. It is rarely symptomatic as it is found incidentally at laparotomy most of the time. Despite advances in diagnostic modalities, it still remains a challenge to the clinician to differentiate it from a neoplasm. It is prudent to differentiate it from neoplastic etiologies, as simple surgical excision can potentially be curative. We discuss the presentation, diagnosis, and treatment of an interesting case of ectopic pancreas presenting as a gastric antral tumor.

Enhancer of zeste homolog 2 (EZH2) plays crucial roles on the development of cells and tissues as well as the progression of prostate cancer (PCa) and castration resistant prostate cancer (CRPC). EZH2 can upregulate and activate progenitor genes including androgen receptor (AR) and the target genes. However, the mechanisms by which EZH2 is regulated in PCa remain elusive. Literature reports that tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) is essential for both normal tissue development and regulation of oncogenic signaling pathways in cancers. In this study, we reported that EZH2 is regulated by PTEN and SKP2 network in PCa. Specifically, we showed that the aberrant upregulation of EZH2 and histone H3 lysine 27 trimethylation (H3K27me3) in both Pten null mouse embryonic fibroblasts (MEFs) in vitro and prostate tumors of Pten null mice in vivo, as compared to the controls. EZH2 levels were negatively correlated with TRAF6 in human PCa cells upon SKP2 dysregulation. Immunofluorescence (IF) staining results showed a co-localization of EZH2 and TRAF6 in nucleus of PC3 cells, and co-immunoprecipitation (co-IP) analysis further confirmed a physical binding of EZH2 and TRAF6 in PC3 cells. Ectopic expression of TRAF6 promoted the K63-linked polyubiquitination of EZH2 to decrease EZH2 and H3K27me3 levels in PCa cells. Conversely, TRAF6 knockdown resulted in a reduction of EZH2 polyubiquitination with an increase of EZH2 and H3K27me3 levels in PCa cells. Furthermore, the catalytically dead mutant TRAF6 C70A abolished the TRAF6-mediated polyubiquitination of human EZH2 in vivo in 293T cells and in vitro in the recombinant human EZH2 protein, as compared with TRAF6 WT. Together, we report for the first time a novel mechanism on EZH2 ubiquitination and an important signaling network of SKP2-TRAF6-EZH2-H3K27me3 in PCa cells. Our findings provide valuable clues on the mechanism and efficiency of targeting EZH2 in PCa and CRPC . Note: This abstract was not presented at the meeting. Citation Format: Wenfu Lu, Shenji Lu, Bo Li, Yingqiu Xie, Michael G. Izban, Billy R. Ballard, Sandeep A. Sathyanarayana, Samuel E. Adunyah, Robert J. Matusik, Zhenbang Chen. EZH2 regulation through lysine 63 linked ubiquitination in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5326. doi:10.1158/1538-7445.AM2017-5326

447 Background: Pancreatoduodenectomy is performed worldwide with significant variations in the perioperative management. The aim of this study is to evaluate the practice patterns across regions of the world. Methods: A pilot cross-sectional 25-item survey questionnaire was electronically distributed using Survey Monkey to IHPBA and AHPBA members between May and August 2015 regarding practice patterns and perioperative care of patients undergoing pancreatoduodenectomy. Results: A total of 285 responses were obtained. The majority of participants were from United States (34.7%), Europe (28.1%) and Asia (14.3%). North American (NA) surgeons are less likely to culture intraoperative bile (36.5% vs. 53.1%, p

449 Background: Pancreatoduodenectomy (PD) is still one of the most complex operations with varied intraoperative techniques and postoperative management. The surgeon volume performing this complex surgery can determine patient outcomes and they might have distinct practice patterns. We aim to compare the practice patterns in perioperative management between high- (HV) and low-volume (LV) hepatobiliary surgeons. Methods: A 25-item survey questionnaire was electronically distributed using Survey Monkey to IHPBA and AHPBA members between May and August 2015 regarding their practice patterns for PD. HV surgeons were defined as those performing greater than 10 PD per year. Results: A total of 285 responses were included (HV, n=229; LV, n=57). The majority of participants were from United States (34.7%), Asia (14.3%) and Europe (28.1%). A significant higher proportion of LV surgeons were observed in Europe (p=0.04) and Asia (p=0.003). LV surgeons are more likely to continue perioperative antibiotics beyond 24 hours postoperatively (57.1% vs. 36.2%, p=0.009) and use more drains (p=0.04), however less likely to routinely measure postoperative drain amylase (73.6% vs. 85.6%, p=0.003). No significant difference was observed regarding management of infection, bile culture, or wound care. Conclusions: Practice patterns are variable between LV and HV pancreatic surgeons. LV surgeons are more likely to prolong prophylactic antibiotics, and use more suction drains, however HV surgeons have closer monitoring for signs of pancreatic leak. Further studies are warranted to elucidate the impact of these variations on surgical outcomes of patients undergoing pancreatoduodenectomy.

448 Background: Pancreatoduodenectomy is the surgical treatment for pancreatic head and periampullary malignancy and is performed by surgeons practicing in all kinds of hospital settings, academic, community and hybrid. The perioperative management is varied amongst surgeons owing to diverse training experience. We aim to evaluate these variations by comparing the hospital settings. Methods: A pilot 25-item survey questionnaire was electronically distributed using Survey Monkey to IHPBA and AHPBA members between May and August 2015 regarding practice patterns and perioperative care of pancreatoduodenectomy. Results: We received 285 responses with participants from academic (56.1%), community (12.6%) or hybrid institutions (31.2%). Most participants performed 10-25 cases annually in each group (46.9%, 50%, 51.7%, respectively). Surgeons from academic institutions routinely culture bile intraoperatively more often than in community institutions (46.3% vs. 22.2%, p

Meckel diverticula are remnants of the omphalomesenteric duct. They have 2% incidence in the general population, are usually asymptomatic, and tend to be diagnosed incidentally. The generally held principle had been that asymptomatic cases do not require resection, as exemplified by a 2008 systematic review of over 200 studies. However, a recent series reported an increased risk of malignancies, and recommended mandatory resection. We present a case of Meckel diverticulitis with concurrent infiltrative appendiceal carcinoid in a patient with right lower quadrant pain.

Robotic colorectal surgery is gaining interest in general and colorectal surgery. The use of the da Vinci(®) Robotic system has been postulated to improve outcomes, primarily by increasing the dexterity and facility with which complex dissections can be performed. We report a large, single institution, comparative study of laparoscopic and robotic colectomies, attempting to better elucidate the benefits of robotic surgery in patients with colorectal disease.We conducted a retrospective review of 171 patients who underwent robotic and laparoscopic colectomies (79 and 92, respectively) at our institution between November 2004 and November 2009. Patients in both groups had well-matched preoperative parameters. All cases were further subdivided by their anatomical location into right-sided and left-sided colectomy, and analysis was performed within these two subgroups. Perioperative outcomes reported include operative time, operative blood loss, time to return of bowel function, time to discontinuation of patient controlled analgesia, length of stay, and intraoperative or postoperative complications.Our results indicate that there is no statistical difference in length of stay, time to return of bowel function, and time to discontinuation of patient-controlled analgesia between robotic and laparoscopic left and right colectomies. Interestingly, the total procedure time difference between the laparoscopic and robotic colectomies was much smaller than previously published accounts (mean 140 min vs. 135 min for right colectomy; mean 168 min vs. 203 min for left colectomy).Our study is one of the largest reviews of robotic colorectal surgery to date. We believe that our results further demonstrate the equivalence of robotic surgery to laparoscopic surgery in colorectal procedures. Future research should focus on surgeon-specific variables, such as comfort, ergonomics, distractibility, and ease of use, as other ways to potentially distinguish robotic from laparoscopic colorectal surgery.

Deep inferior epigastric artery perforator (DIEP) flaps have become an attractive option for autologous breast reconstruction. The internal mammary artery (IMA) is the usual artery of choice for reconstruction. Unfortunately, there are certain situations when the IMA may not be suitable for usage as in previous radiation or diminutive size. Several options have been documented, such as using the thoracodorsal vessels. In this case report, we report usage of the distal and proximal ends of a contralateral single mammary artery to supply antegrade and retrograde flow to bilateral DIEP flaps. With increasing complexity of patient populations, the use of alternate approaches to recipient vessel in DIEP reconstruction becomes essential for effective outcomes.

RESULTS: Among 17 consecutive patients who underwent DPCAR, the LGA was preserved in 13 patients and reconstructed in 4 patients. Major postoperative complications were observed in 7 cases (41%). A pancreatic fistula (Grade B/C) or delayed gastric emptying (Grade B/C) occurred in 7 (41%) and 2 (12%) cases, respectively. The overall R0 resection rate was 94% (16/17). Ten cases developed recurrences (liver, n 1⁄4 4; lymph nodes, n 1⁄4 2; peritoneal dissemination, n 1⁄4 2; lung, n 1⁄4 1; local recurrence, n 1⁄4 1). The overall survival rates were 78% and 54% at 1 and 3 years after operation.

Background and Objectives: Within the past few years, there has been a push for an even more minimally invasive approach to biliary disease with the adoption of single-incision laparoscopic cholecystectomy. We sought to compare 4 individual surgeon experiences to define whether there exists a learning curve for performing single-incision laparoscopic cholecystectomy. Methods: We performed a retrospective review 290 single-incision laparoscopic cholecystectomies performed by a group of general surgeons, with varying levels of experience and training, at 3 institutions between May 2008 and September 2010. The procedure times were recorded for each single-incision laparoscopic cholecystectomy, ordered chronologically for each surgeon, and subsequently plotted on a graph. The patients were also combined into cohorts of 5 and 10 cases to further evaluate for signs of improvement in operative efficiency. Results: Of the 4 surgeons involved in the study, only 1 (surgeon 4, laparoscopic fellowship trained with