Citations

134 Background: Brain metastasis (BM) is an uncommon site of failure in patients (pts) with esophageal cancer (EC) with reported rates between 1-6%. EC pts are living longer with the wider adoption of trimodality therapy and, as with other malignancies, this may change the patterns of failure. We evaluated the incidence and outcomes of BM in EC at Mayo Clinic in Arizona. Methods: A retrospective review identified pts who developed BM from cancer of the esophagus or gastroesophageal junction. A total of 321 patients treated for stage I-IV EC (adenocarcinoma, n = 273; squamous, n = 46; small cell, n = 2) were identified between 1997 and 2012. Fisher’s exact test was used for comparisons. Actuarial survival was calculated using Kaplan-Meier analysis. Results: BM developed in 13 pts (4%), all of whom had adenocarcinoma. Nine pts initially presented with T3 and/or node-positive disease. Four pts presented with metastatic disease to other sites, but only 1 of this group was diagnosed with BM at initial presentation. The median time from initial diagnosis to BM detection was 12 months (range 0-40). All pts were symptomatic at diagnosis. BM was solitary in 6 pts, multiple in 6 pts, and unknown in 1 pt. The posterior fossa was involved in 9 pts. The brain represented the first site of failure in 9 pts. Treatment included surgical resection (n = 5), stereotactic radiosurgery (n = 4), and whole brain radiotherapy (n = 9). Median overall survival was 24 months from initial diagnosis and 5 months from BM detection. Among pts with adenocarcinoma, 3/119 (2.5%) were diagnosed between 1997-2006 compared to 10/154 (6.5%) between 2007-2012 (P = 0.1). Conclusions: The brain remains an uncommon site of failure among pts with EC. A recent series reported an incidence of BM in 13% of pts, raising the possibility of a changing failure pattern. In our series, BM was detected in only 4% of pts. Our study is suggestive of a trend towards increased incidence of BM in more recent years, although it did not reach statistical significance and could be a consequence of the retrospective nature of the study. Both series found BM limited only to pts with adenocarcinoma, and a possible association has been reported between HER-2 overexpression and BM in EC. Therefore, BM in EC may be an interesting area for future study.

20 Background: Esophageal adenocarcinoma (EAC) incidence is rising and prognosis is uniformly poor, even with early stage disease. Barrett esophagus (BE) serves as a premalignant marker for EAC, with an estimated progression of 0.5% per year. Low-grade (LGD) and high-grade dysplasia (HGD) confer a higher risk of progression, providing an opportunity for intervention and surveillance. Aims: To evaluate a large cohort of patients undergoing endoscopic evaluation of BE and thereby better understand the natural history of BE and dysplasia. Methods: A retrospective review of endoscopic databases was conducted for all patients with the diagnosis of BE undergoing upper endoscopy at a tertiary academic medical center from 1991-2010. All endoscopy and accompanying pathology reports were reviewed. Only those patients with 2 biopsies documenting specialized intestinal metaplasia were analyzed. Results: 848 patients underwent upper endoscopy for evaluation of BE. Of these, 674 patients met inclusion criteria, at a mean follow up of 66.6 months. Table 1 depicts the distribution of patients according to their histology at presentation. 22 (3.2%) patients presented with established EAC, while EAC developed in 51 (7.6%). Of patients with HGD, LGD, or no dysplasia (ND) at presentation, EAC ultimately developed in 30.6%, 6.6%, and 2.7%, respectively. EAC developed in 4 patients despite RFA treatment for ND (2) or LGD (2). HGD developed in 6 such patients after treatment for ND (3) and LGD (3). Only 1 patient in each RFA-treated cohort required esophagectomy, while the others cleared dysplasia or EAC with continuous treatment. Conclusions: In this large cohort of patients with Barrett’s esophagus, higher grade of dysplasia at first endoscopy was associated with development of EAC. Continuous surveillance during and after endoscopic treatment is necessary and often results in clearance of dysplasia and EAC. [Table: see text]

110 Background: Anastomotic leaks can occur after esophagectomy and optimal management after minimally invasive esophagectomy (MIE) is not well defined. We reviewed endoscopic management of leaks after MIE in patients undergoing trimodality therapy at Mayo Clinic Arizona. Methods: Records of patients undergoing MIE from November, 2006 to February, 2015 were reviewed after appropriate IRB approval. Results: 148 patients underwent MIE including 136 (91.8%) thoracic and 12 (8.1%) cervical anastomoses. Clinically significant anastomotic leaks were observed in 13 (8.8%) patients with 2 (16%) cervical and 11 (8%) thoracic anastomosis at a median of 6.1 days (0-14). 11 (11%) patients treated with neoadjuvant chemoradiotherapy experienced esophageal leak and 2 who did not receive chemoradiotherapy (4%). For treatment of anastomotic leaks, 10 patients underwent VATS with pleural space irrigation and chest tube replacement, and 11 patients underwent stent deployment at the anastomosis for repair. Stents were placed such that the fistula/leak was in the fully covered portion with the greater portion of the stent residing in the esophageal remnant. Stents were removed at a mean of 54 days (28-114). In 2 patients, overgrowth into the stent body required stent-in-stent placement (fully covered) with removal of both stents. Stents were successful at sealing all leaks. Conclusions: Leaks after MIE represent a small, but significant, morbidity in MIE. The majority can be managed by endoscopic stent placement. Stenting is an effective management tool for postoperative leaks in locally advanced esophageal malignancies.

158 Background: Esophageal cancer patients (pts) require multidisciplinary management involving thoracic and general surgeons, medical and radiation oncologists, gastroenterologists and psychiatrists. Pts navigate complex medical discussions and endure challenges to nutrition, body image, swallowing mechanics, energy level and weight, mood, and performance status. Coordination of care is complicated by multiple sites of pt entry, complex scheduling requirements, and incomplete information at multidisciplinary consultation. A nurse navigator to coordinate the patient experience may optimize treatment and improve outcomes, quality of life and patient satisfaction. Methods: The nurse navigator evaluates all pt records prior to initial appointment and coordinates scheduling, records acquisition, testing and specialty appointments. The nurse navigator serves as a liaison with pts throughout the course of care and provides a patient navigation book (PNB) as a central source for patient-directed information and record keeping. Benchmarks compared before and after creation of the nurse navigator position include: (1) time from appointment request to multidisciplinary evaluation and start of treatment; (2) completeness of medical records and data (scans, pathology slides); (3) patient awareness of support services for themselves and caregivers; (4) utilization of the PNB; (5) number and frequency of interim hospitalizations and emergency room visits; (6) patient, caregiver, and physician satisfaction. Results: From January to July 2012, 27 gastroesophageal cancer pts have been followed by the nurse navigator. Most of these patients remain on active treatment, hence benchmark analysis is ongoing. Metrics thus far suggest improvement in time to treatment start and awareness of patient resources, use of the PNB and patient satisfaction. Conclusions: Esophageal cancer pts undergo complex and toxic multimodality therapy with curative intent. A dedicated nurse navigator may improve the patient experience, optimize adherence to guideline based therapy and appropriate timeframes and provide continuity to pts undergoing multidisciplinary treatment.

Introduction: The increasing use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology to examine pancreatic neoplasms has led to an increase in the diagnosis of metastases to the pancreas. Renal cell carcinoma (RCC) is the most common metastasis to the pancreas. Our study examines 33 cases of metastatic RCC to the pancreas sampled by EUS-FNA from four large tertiary care hospitals. Materials and Methods: We searched the cytopathology database for RCC metastatic to the pancreas diagnosed by EUS-FNA from January 2005 to January 2015. Patient age, history of RCC, nephrectomy history, follow-up postnephrectomy, radiological impression, and EUS-FNA cytologic diagnosis were reviewed. Results: Thirty-three patients were identified. The average age was 67.5 years (range, 49–84 years). Thirty-two patients had a previous documented history of RCC. One patient had the diagnosis of pancreatic metastasis at the same time of the kidney biopsy. Thirty-one patients had been treated with nephrectomy. Twenty-seven patients were being monitored annually by computed tomography or magnetic resonance imaging. Twenty-five patients had multiple masses by imaging, but 8 patients had a single mass in the pancreas at the time of EUS-FNA. EUS-FNA of 20 cases showed classic morphology of RCC. Thirteen cases had either “atypical” clinical-radiologic features or morphologic overlaps with primary pancreatic neoplasms or other neoplasms. Cell blocks were made on all 13 cases and immunochemical stains confirmed the diagnosis. Conclusions: EUS-FNA cytology is useful for the diagnosis of metastatic RCC to the pancreas. Cytomorphology can be aided with patient history, imaging analyses, cell blocks, and immunochemical stains.

Abstract The three-dimensional (3D) structure of the cell and its nucleus is intricately associated with cellular function. Aberrations and heterogeneity in cellular and nuclear morphology serve as diagnostically important cues to identify malignant transformation. However, current cytopathology practice is predominantly based on a qualitative, 2D assessment of cellular morphology that may bias the diagnosis. We utilized the Cell-CT® platform to perform single-cell, optical tomography imaging and generate 3D cell images with isotropic, sub-micron spatial resolution. We developed custom image analysis tools to accurately quantify 3D cell and nuclear morphology. We used these measures to characterize the morphological heterogeneity within and among epithelial cell populations, and to identify morphological descriptors that are reliably predictive of cell state. We assessed the efficacy of our approach relative to conventional 2D assessment (at 40x magnification) to detect malignant transformation in immortalized and primary normal-cancer cell line pairs from human esophagus and breast epithelia. We observed the 3D method of assessment to provide a consistently superior performance (sensitivity and specificity) in predicting malignant transformation. Further, some widely used diagnostic parameters, such as nuclear size or nucleus-to-cytoplasm ratio, did not always exhibit the highest predictive power in 3D space. The availability of 3D morphological information also provided novel insights on intra-population morphological heterogeneity in both normal and cancer cell populations. Our results emphasize the need to incorporate 3D morphological information into standard pathological practice. Citation Format: Vivek Nandakumar, Stephanie Helland, Jessica H. Han, Geriann Davis, Brian A. Ashcroft, Thai H. Tran, Ting Li, Karen S. Anderson, Rahul Pannala, Joseph R. Mikhael, David E. Fleischer, Roger H. Johnson, Kimberly J. Bussey, Deirdre R. Meldrum. Quantifying three-dimensional cellular morphology and its heterogeneity in epithelial cancers by single-cell optical tomography. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4297. doi:10.1158/1538-7445.AM2014-4297

Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.