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Question: A 68-year-old Caucasian man was admitted with a 1-week history of hematochezia and hemoptysis. At an outside community hospital he was found to have a hemoglobin of 9.6 g/dL and hematocrit of 28.8%, but was otherwise asymptomatic. He underwent endoscopy which demonstrated a 1- to 1.5-cm raised lesion actively oozing fresh blood in the proximal descending duodenum. Argon plasma coagulation was applied, but the patient continued to bleed, requiring transfusions and repeat coagulation performed 48 hours later. He was then referred to our center for further evaluation.

Eradication of Helicobacter pylori appears to reduce gastric cancer incidence. We examined the effect of successful H pylori therapy on histology, phenotype of gastric intestinal metaplasia (GIM) (complete vs incomplete), and expression of several biomarkers related to carcinogenesis.Ninety-six H pylori-positive patients from Japan were treated successfully and followed up prospectively over 4 years with yearly endoscopy and were classified into 3 groups: group CG, chronic gastritis without GIM (n = 36); group IM, chronic gastritis with GIM (n = 33); group DYS, and GIM with dysplasia/cancer in a different location of the stomach (n = 27). A total of 288 endoscopic procedures were performed. Histology, mucin-histochemistry, and immunoperoxidase assays using monoclonal antibodies (mAbs) for cell phenotype (monoclonal antibody Das-1/colonic) and for neoplasia (TC22 and p53) were performed.The GIM histologic score was higher in group DYS than in group IM (P.05) and group CG (P.0001). The GIM scores did not change in groups IM and DYS over 4 years. mAb Das-1 reactivity was higher in group DYS (63%) than in group IM (39%) and group GC (0%). After eradication of H pylori, mAb Das-1 reactivity disappeared in 40% of patients (P.0001) despite the unchanged GIM scores, and regression of TC22-4 was noted in the same patients.H pylori eradication does not reduce the histologic GIM score, but changes the cellular phenotype of GIM. This change of phenotype may be an important factor in the reduction of cancer incidence after eradication of H pylori.

This paper presents four new circuit techniques that reduce the parasitic bipolar junction transistor (BJT) effect in digital dynamic logic circuits in partially depleted silicon-on-insulator (PD-SOI) technology. Simulation results have shown the proposed schemes to be effective at various operating voltages. Fully functional test circuits, incorporating some of the proposed techniques, have been designed, fabricated and tested in a 130nm IBM PD-SOI technology. The measured silicon hardware data validate the simulation predictions and have demonstrated that the new techniques can be easily incorporated to improve the robustness of PD-SOI dynamic logic circuits.

This paper presents a new power gating structure with robust data retention capability using only one single double-gate device to provide both power gating switch and virtual supply/ground diode clamp functions. The scheme reduces the transistor count, area, and capacitance of the power gating structure, thus improving circuit performance, power, and leakage. The scheme is compared to the conventional power gating structure via mixed-mode physics-based two-dimensional numerical simulations. Analysis of virtual ground bounce for the proposed scheme is also presented.

An integrated computer-aided design (CAD) framework for evaluating MOSFET and layout parasitic extraction (LPE) models and circuit simulators used in the timing and power analysis of CMOS products is presented. This unified CAD methodology builds a step-wise understanding of the underlying parameter values in the models and their impact on circuit performance. A number of circuit experiments are included to extract the contributions of key MOSFET parameters and physical layout sensitive parasitic elements from circuit simulation results. This CAD setup thus allows easy and detailed comparison of different technologies, device models, and LPE tools to prevent possible bugs in the software as well as inaccuracies in device and parasitic models and timing tools. The software code to carry out the circuit simulations, analysis, and display of the results in an automated fashion has been specifically developed to support this framework. Some of the experiments designed for this work are also placed on the product chip for model-to-hardware correlation. The comparison of the hardware data to the model predictions points to the sources of any discrepancies and aids in tuning the product design to reflect changes in the technology as part of an overall design for manufacturing (DFM) platform

Test structures utilizing ring oscillators to monitor MOSFET ac characteristics for digital CMOS circuit applications are described. The measurements provide information on the average behavior of sets of a few hundred MOSFETs under high speed switching conditions. The design of the ring oscillators is specifically tailored for process centering and monitoring of variability in circuit performance in the manufacturing line as well as in the product. The delay sensitivity to key MOSFET parameter variations in a variety of ring oscillator designs is studied using a compact model for partially depleted silicon on insulator(PD-SOI) technology, but the analysis is equally valid for conventional bulk Si technology. Examples of hardware data illustrating the use of this methodology are taken primarily from experimental hardware in the 90-nm CMOS technology node in PD-SOI. The design and data analysis techniques described here allow very rapid investigation of the sources of variations in circuit delays.

Objectives: Gastric intestinal metaplasia (GIM) associated with H. pylori (HP) has been considered a premalignant lesion. However, GIM phenotype associated with HP infection and gastric cancer is unclear. The expression of COX-2 in relation to GIM phenotype is also unknown. Methods: We evaluated cellular phenotype and COX-2 expression in the GIM from HP-positive and -negative patients from Japan in the absence of gastric cancer (n = 31) by using a colon epithelium specific monoclonal antibody (mAb Das-1) and anti-COX-2 antibody. COX-2 expression was also examined in patients with gastric cancer (n = 34), both in the cancer and in the GIM areas away from the cancer field. Results: Sixty-eight percent of HP-positive GIM reacted with mAb Das-1, whereas the reactivity in the HP-negative GIM was only 25% (P < 0.001). The COX-2 expression was present in 32% of HP-positive GIM and in only 9% of HP-negative GIM (P < 0.001). In the cancer group, COX-2 expression was localized both in the cancer area (94%) and in the GIM (82%) away from the cancer. Each of the COX-2-positive tissue was also positive to mAb Das-1. Conclusion: HP infection is highly associated with the development of colonic-phenotype of GIM, and about half of them expressed COX-2. COX-2 expression was frequent in both gastric cancer and the GIM adjacent to the cancer. The results suggest that the presence of mAb Das-1 and COX-2 reactivity in the GIM identify the subgroup of patients who may be at risk for gastric cancer and may need close surveillance.

Leakage power and input pattern dependence of leakage for extremely scaled (L/sub eff/=25nm) double-gate (DG) circuits are analyzed, compared with those of conventional bulk-Si counterpart. Physics-based numerical two-dimensional simulation results for DG CMOS device/circuit power are presented, identifying that DG technology is an ideal candidate for low-power applications. Unique DG device features resulting from gate-gate coupling are discussed and effectively exploited for optimal low-leakage device design. Design tradeoffs for DG CMOS power and performance are suggested for low-power and high-performance applications. Total power consumptions of static and dynamic circuits and latches for DG device, considering state dependency, show that leakage currents for DG circuits are reduced by a factor of over 10/spl times/, compared with bulk-Si counterpart.

Background: Some forms of gastric intestinal metaplasia (GIM) may be precancerous but the cellular phenotype that predisposes to gastric carcinogenesis is not well characterised. Mucin staining, as a means of differentiating GIM, is difficult. A monoclonal antibody, mAb Das-1 (initially called 7E12H12), whose staining is phenotypically specific to colon epithelium, was used to investigate this issue. Methods: Using mAb Das-1, by a sensitive immunoperoxidase assay, we examined histologically confirmed GIM specimens from two countries, the USA and Japan. A total of 150 patients comprised three groups: group A, GIM (fields away from the cancer area) from patients with gastric carcinoma (n=60); group B, GIM with chronic gastritis (without gastric carcinoma) (n=72); and group C, chronic gastritis without GIM (n=18). Results: Fifty six of 60 (93%) patients with GIM (both goblet and non-goblet metaplastic cells) from group A reacted intensely with mAb Das-1. Cancer areas from the same 56 patients also reacted. In contrast, 25/72 (35%) samples of GIM from patients in group B reacted with mAb Das-1 (group A v B, p

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with a propensity for metastasis and drug resistance. To overcome this and improve the outcome of patients with PDAC, there is an urgent need to elucidate the molecular mechanisms of metastasis in which cancer stem cells (CSCs) may play a role. Prrx1, a homeobox transcription factor has been identified by us, as a key molecule involved in pancreatic development, regeneration and early carcinogenesis (Reichert et al. Genes and Development 2013). Furthermore, we have reported recently that Prrx1 isoform switching governs EMT-MET plasticity to regulate PDAC invasion and metastasis (Takano et al. Genes and Development 2016). Herein, we examined that the correlation between the two Prrx1 isoforms and putative CSC markers to investigate the role of Prrx1 on pancreatic CSC functions. Materials and Methods: Mouse pancreatic ductal cell lines were isolated and established from Pdx1Cre mice (normal pancreatic ductal cells), Pdx1Cre;KrasG12D/+ mice (PanIN cells), Pdx1Cre;KrasG12D/+;p53R175H/+ mice (primary and metastatic PDAC cells). Either Prrx1a and Prrx1b was overexpressed by lentiviral transduction in each cell line with controls. Prrx1 knockdown was done in primary PDAC cells and their matched liver metastatic cells by two isoform specific siRNAs. We immunophenotyped putative pancreatic CSCs using antibodies against CSC markers (CD133, CD44, CD24 and Epcam) by flow cytometry. These subpopulations of cells were evaluated in 3D cultures, invasion assays and single-pancreatosphere formation assays. Additionally, we evaluated the expression of pancreatic CSC markers in Prrx1a and Prrx1b overexpressing and knockdown cells by qRT-PCR and flow cytometry. Results: CD133High cells and CD44HighCD24High cells are expressed highly in metastatic PDAC cells compared to primary PDAC cells. CD133High cells form spheroid cysts and CD133Low cells form spindle-shaped cells in 3D culture. CD133High cells demonstrate more invasiveness and higher self-renewal capacity compared to CD133 Low cells. The percentage of CD133High cells, CD44HighCD24High cells and EpCAMHigh cells are increased significantly in Prrx1a overexpressing primary PDAC cells. However, these cells are decreased in Prrx1a knockdown metastatic cells. Contrary to this, these subpopulation of cells are significantly decreased in Prrx1b overexpressing primary PDAC cells, and increased in Prrx1b knockdown metastatic cells. These data suggest that Prrx1a might regulate pancreatic CSC functions in metastatic PDAC cells. Conclusion: Prrx1a may be associated with a subpopulation of pancreatic cancer cells that have features of cancer stem cells. This may influence metastatic properties of pancreatic cancer cells to the liver. Citation Format: Shigetsugu Takano, Maximilian Reichert, Hideyuki Yoshitomi, Basil Bakir, Koushik K. Das, Steffen Heeg, Shingo Kagawa, Hiroaki Shimizu, Masayuki Ohtsuka, Katsunori Furukawa, Masaru Miyazaki, Anil K. Rustgi.{Authors}. Prrx1 isoforms regulate pancreatic cancer stem cell functions during pancreatic cancer progression. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B30.

Static Random Access Memories (SRAMs) are key components of modern VLSI designs and a major bottleneck to technology scaling as they use the smallest size devices with high sensitivity to manufacturing details. Analysis performed at the "schematic" level can be deceiving as it ignores the interdependence between the implementation layout and the resulting electrical performance. We present a computational framework, referred to as "Virtual SRAM Fab", for analyzing and estimating pre-Si SRAM array manufacturing yield considering both lithographic and electrical variations. The framework is being demonstrated for SRAM design/optimization in 45nm nodes and currently being used for both 32nm and 22nm technology nodes. The application and merit of the framework are illustrated using two different SRAM cells in a 45nm PD/SOI technology, which have been designed for similar stability/performance, but exhibit different parametric yields due to layout/lithographic variations. We also demonstrate the application of Virtual SRAM Fab for prediction of layout-induced imbalance in an 8T cell, which is a popular candidate for SRAM implementation in 32-22nm technology nodes.

Although a protective role for mesalamine against colon cancer in ulcerative colitis has been shown epidemiologically, its molecular mechanism is unknown. We cloned and sequenced a novel human tropomyosin (hTM) isoform, TC22, which is an alternatively spliced variant of normal epithelial hTM isoform 5 (hTM5), identical apart from 25 C-terminal amino acids. TC22 is expressed in 100% of colorectal carcinoma but is not expressed in normal colon epithelial cells. To explore a molecular mechanism of chemoprevention, we examined the effect of mesalamine on TC22 expression using LS180 colon cancer cells. Expression of hTM5 and TC22 was investigated at the protein and gene levels by fluorescence-activated cell sorting and real-time reverse transcription-polymerase chain reaction. Small interference RNA (siRNA) against the TC22 variant were transfected into LS180 colon cancer cells, reducing protein and transcript levels by 45 to 50%. Mesalamine or sulfasalazine (2 mM), but not sulfapyridine, significantly (p < 0.02-0.006) reduced the expression of the TC22 transcript and significantly (p < 0.05 to

The ability to fully leverage future CMOS technologies will require a proactive approach to aggressively manage power while characterizing and mitigating the various sources of technology uncertainty. Adaptive techniques that span the full design stack across technology, circuits, and systems/software are required for building future reliable systems. Moreover, the emerging trend of low-power, multi-core-based systems requires very high transistor density and will help drive the transition to unconventional non-planar silicon devices with reduced short channel effects. An integrated design approach between technology development, VLSI design, design automation tools, and micro-architecture is required for optimum system design.

This paper demonstrates that regular-Vt long channel stacked and optimally tapered headers/footers can be used for ultra-low leakage circuits at Iow-VddS with dramatic leakage reduction over earlier schemes. Our proposed schemes take advantage of the fact that the leakage saving of two stacked OFF devices as compared to a single OFF device increase rapidly when the sub-threshold slope reduces (improves).

A new test structure utilizing a differential technique for measuring CMOS latch delay with sub-ps time resolution is described. The latch delay and error count in the metastability region are measured as a function of clock-data delay which can be incremented in 0.1 ps steps. This compact test structure is configured to be placed in the scribe line for characterizing different latch designs and correlating their behavior with model predictions.

Introduction: The Ets-transcription factor Etv1 is involved in epithelial-mesenchymal interactions during pancreatic development and shows enhanced expression in PanIN as well as in pancreatic ductal adenocarcinoma (PDAC). Therefore, we aimed to identify the mechanistic roles of Etv1 in EMT and invasion in PanIN and PDAC. Methods: Cells were isolated from Pdx1Cre;KrasG12D/+-mice (PanIN) and Pdx1Cre;KrasG12D/+;p53R175H/+-mice (PDAC) and lentiviral tranduction was used to induce overexpression or knockdown (shRNA) of Etv1, respectively. Cells were grown in 3D organotypic culture to analyze morphology and growth behavior. Invasion and sphere formation (self-renewal) assays were performed. FACS-sorting was used to isolate CD44+/CD24+ cells as a putative cancer stem cell population in PDAC and analyzed for Etv1 expression. To assess the role of Etv1 in PDAC in vivo, orthotopic pancreatic xenograft transplantation of Etv1 overexpressing PDAC cells was performed. Results: Etv1 overexpression in PanIN cells grown in 3D-organotypic culture induces a spindle shaped morphology and highly perturbed cyst architecture in contrast to control PanIN cells that form spheroid cysts that resemble normal pancreatic ductal structures. Concurrently and consistently, EMT-related genes (snail, twist, zeb1 and zeb2, as well as vimentin and N-cadherin) were found upregulated by >2-fold in PanIN-mEtv1 cells. Moreover, the expression of Mmp3 and Mmp9 was significantly increased. Functionally, the invasive capacity of PanIN-mEtv1 cells was more than twice that of control cells; knockdown of Etv1 in PDAC-cells significantly abrogated their invasive capacity. In sphere forming assays PanIN-mEtv1 cells revealed an increased self-renewal capacity, whereas sphere formation is reduced by knockdown of Etv1 in PanIN as well as in PDAC cells. FACS-sorting and subsequent expression analysis revealed increased Etv1 levels in the putative cancer stem cell population of CD44+/CD24+ PDAC-cells. Data from orthotopic xenografts showed significantly larger tumors, significantly increased stromal expansion measured by trichrome staining, and increased local tumor invasion in Etv1-overexpressing cells compared to controls. The increased stromal expansion significantly correlated to the increased tumor volume observed in Etv1 over-expressing xenografts. Conclusion: Our novel data indicate that Etv1 induces EMT as well as invasion both in vitro and in vivo and mediates self-renewal capacity of premalignant cells derived from PanIN- as well as PDAC-cells. Our in vivo data suggest a role for Etv1 in expanding the stromal compartment. These striking data suggest that Etv1 is biologically important in EMT. In vivo experiments with conditional knockout of Etv1 in Pdx1Cre;KrasG12D/+;p53R175H/+-mice are ongoing to further elucidate the role of Etv1 in PanIN and PDAC initiation and progression. Citation Format: Koushik K. Das, Steffen Heeg, Maximilian Reichert, Shigetsugu Takano, Basil S. Bakir, Gregory P. Botta, Christopher Hahn, Andrew D. Rhim, Anil K. Rustgi. The Ets-transcription factor Etv1 induces epithelial-mesenchymal transition (EMT) and invasion as well as expands the stromal compartment in vivo. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A46.

Introduction: The exocrine pancreas comprises a branched network of ducts that are connected to acini and lined by a monolayered epithelium that derives from the endoderm and is surrounded by mesenchyme. The formation and maturation of pancreatic ductal cells during branching morphogenesis is controlled by a complex hierarchy of transcription factors, which is not fully understood. The Ets-transcription factor Etv5 has been reported to play an important role during the development of organs that undergo branching morphogenesis such as mammary and salivary glands. We therefore aimed to characterize the functional role of Etv5 in pancreatic ductal development and differentiation. Methods: Cells were isolated from wild-type mouse pancreata and lentiviral transduction was used to induce Etv5 overexpression. Cells were grown in 3D organotypic culture and analyzed with time lapsed microscopy for morphology and dynamics in the formation of duct-like cystic structures. Differentiation status of cells grown in 3D was analyzed by immunofluorescence-staining (IF) and qPCR. To asses the role of Etv5 in the normal mouse pancreas and its role in inflammation and regeneration in vivo, Pdx1cre;Etv5-/-; RosaYFP mice were generated and aged up to six months and subjected to a cerulein induced acute pancreatitis protocol. Results: Normal pancreatic ductal cells grown in 3D-organotypic culture form spheroid cysts that resemble pancreatic ductal structures. Etv5 overexpression leads to early and exuberant formation of spheroid cysts within 2 days after seeding. Time-lapse microscopy demonstrated a significantly increased movement of cellular structures along the cyst as well as fusion of cysts into larger tubular structures. mRNA analysis of cysts harvested at day 7 displayed a strong upregulation of Sox9 and Foxa2, important regulators of ductal differentiation. Concurrently, E-cadherin was upregulated significantly whereas N-cadherin was downregulated indicating the terminal differentiation of these cells. IF-staining revealed co-localization of Etv5 and Sox9 in spheroid cysts of Etv5-overexpressing cells. Knockdown of Sox9 in Etv5-overexpressing cells with siRNA partially abrogated the formation of tubular structures and disrupted cyst architecture. Etv5 knockout mice (Pdx1Cre;Etv5-/-) were generated and we performed a cerulein-induced acute pancreatitis model. We found significantly elevated levels of serum amylase in Etv5-/- mice on Days 1 and 3 of the protocol. In a semiquantitative, blinded review of the histology, there was significantly more intense edema, inflammation, vacuolization and necrosis in Etv5-/- mice in all time points, which was also confirmed by quantitative amylase area scoring. Conclusion: Our data suggest a novel role for Etv5 in pancreatic ductal morphogenesis and lumen formation that is at least in part mediated by Sox9. In addition, our data suggests that the loss of Etv5 expression increases susceptibility to pancreatitis and results in persistent pancreatitis with delayed regeneration. Citation Format: Koushik K. Das, Steffen Heeg, Maximilian Reichert, Shigetsugu Takano, Basil S. Bakir, Gregory P. Botta, Christopher Hahn, Andrew D. Rhim, Anil K. Rustgi. Ets transcription factor Etv5 regulates ductal morphogenesis and differentiation in association with Sox9 in vitro and increases susceptibility and delays recovery from pancreatitis in vivo. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A11.

NA not assessed, INT intensive therapy, NPDR non proliferative diabetic retinopathy, a Values are numbers (%) or mean (SEM) unless stated otherwise. b CAN prevalence is defined as any of: R-R variation 300 mg/day, renal transplant or dialysis. Table 2. Multiple Variable Predictor Models for Delayed Gastric Emptying in Type 1 Diabetes Mellitus

Several novel schemes of implementing MTCMOS circuits in hybrid UTSOI-epitaxial CMOS structures are proposed and analyzed through comprehensive circuit simulations. The schemes offer intrinsic high circuit density and facilitate header/footer body biasing techniques for performance enhancement and leakage reduction. The effectiveness in improving active-mode performance, and reducing virtual supply bounce and standby leakage power is demonstrated.

This paper presents a new power gating structure with robust data retention capability using only one single double-gate device to provide both power gating switch and virtual supply/ground diode clamp functions. The scheme reduces the transistor count, area, and capacitance of the power gating structure, thus improving circuit performance, power, and leakage. The scheme is compared with the conventional power gating structure via mixed-mode physics-based two-dimensional numerical simulations. Analysis of virtual ground bounce for the proposed scheme is also presented.

Power management has become a key constraint in the design of modern digital VLSI chips. Moreover, with minimum transistor dimensions reaching 100-nm and below, traditional scaling has slowed down. The ITRS roadmap has indicated that device mobility enhancement would be necessary to maintain the generational performance improvement in the sub-100nm VLSI era. This paper presents a comprehensive analysis of the popular low-leakage power MTCMOS circuit technique in various emerging technologies with enhanced-mobility PFETs.

This paper discusses the analysis and design of digital CMOS circuits in hybrid SOI-epitaxial technology with different crystal orientations. Various mobility enhancement schemes, such as strained Si channel devices, utilization of process/structure induced stresses, and use of different crystal orientation, have been proposed.

Objectives The aim of this study was to determine whether specialized intestinal metaplasia recurs after complete laser ablation and to evaluate the persistence of colon epithelial protein in esophageal mucosa after laser ablation as a predictor of recurrence. Methods A total of 31 patients with specialized intestinal metaplasia (Barrett’s esophagus) underwent laser photoablation. Investigators without knowledge of treatment status evaluated serial hematoxylin and eosin–stained slides, Alcian blue–stained slides, and immunohistochemistry for the detection of colon epithelial protein (mAb Das-1). Results Endoscopic ablation of specialized intestinal epithelium was accomplished in 21 patients after 6.5 ± 1.2 laser sessions. Complications included one perforation, one UGI bleed and one stricture. Of eight post-laser recurrences, seven were successfully re-ablated; one developed adenocarcinoma requiring esophageal resection. Cardia-type mucosa was present by biopsy at the time of complete ablation in all eight recurrent cases despite a normal endoscopic appearance. Colon epithelial protein was detected in all 31 patients before ablation, six of 21 completely ablated patients before they recurred and all eight recurrences. Only two of 15 patients, colon epithelial protein negative at the time of complete ablation, developed recurrent Barrett’s esophagus. Thus, cardia-type mucosa and persistent colon epithelial protein staining after complete ablation of specialized intestinal epithelium were predictors of future recurrence (p Conclusions Specialized intestinal epithelium was ablated by neodymium:yttrium-aluminum-garnet laser but recurred in eight of 21 (38%) of patients. Colon epithelial protein was present in all primary (31 of 31) and all recurrent (eight of eight) Barrett’s esophagus. Recurrent specialized intestinal metaplasia may be deep to squamous epithelium. Replacement of specialized intestinal mucosa by cardia-type mucosa and persistence of colonic epithelial protein are predictors of recurrent specialized intestinal mucosa before its endoscopic or histological detection. Laser ablation of Barrett’s epithelium is an investigational intervention that should be restricted to research protocols.

invasive carcinoma. A median time to recurrence after resection was 31 months (range 183) for non-invasive tumors and 11 months (range 1-145) for those with invasion (P=0.05). No clinical or pathological predictors of recurrence were found for non-invasive IPMNs. Among invasive tumors, predictors for recurrence were macroscopic invasion (P=0.003), N1 status (P

G A A b st ra ct s There was no serous cystadenocarcinoma reported. Surgical indications (470 indications for 410 patients) were: uncertain diagnosis with mucinous cystadenoma or neuroendocrin tumor or IPMN (n=261, 63%), specific or mainly non specific symptoms (n=102, 25%), increase in size (n=51, 12%) or adjacent organ compression (n=30, 7%). Five patients died post operatively (0.8%), related mortality in Group 3 was 0% (NS). SCA related mortality is nil, whereas operative mortality is not. SCA natural history is benign in the vast majority of cases. Slow increase in size is observed in half of the patients and is responsible for few complications. Uncertainty diagnosis is a too frequent surgical indication even though reliable diagnostic criteria have been established. SCA should be followed and not operated on unless clearly justified by clinical evolution.

Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes that correlate with histological grades and risks for malignant transformation. mAb Das-1 is a monoclonal antibody against a colonic epithelial phenotype that is reactive to premalignant conditions of the upper GI tract. We sought to assess the ability of mAb Das-1 to identify IPMN with high risk of malignant transformation.mAb Das-1 reactivity was evaluated in 94 patients with IPMNs by immunohistochemistry. Lesional fluid from 38 separate patients with IPMN (n=27), low-grade non-mucinous cystic neoplasms (n=7) and pseudocysts (n=4) was analysed by ELISA and western blot.Immunohistochemistry-Normal pancreatic ducts were non-reactive and low-grade gastric-type IPMN (IPMN-G) (1/17) and intermediate-grade IPMN-G (1/23) were minimally reactive with mAb Das-1. In contrast, mAb Das-1 reactivity was significantly higher in high-risk/malignant lesions (p0.0001) including: intestinal-type IPMN with intermediate-grade dysplasia (9/10); high-grade dysplasia of gastric (4/7), intestinal (12/12), oncocytic (2/2) and pancreatobiliary types (2/2); and invasive tubular (8/12), colloid (7/7) and oncocytic (2/2) carcinoma. The sensitivity and specificity of mAb Das-1 for high-risk/malignant IPMNs were 85% and 95%, respectively. Lesional fluid-Samples from low- and intermediate-grade IPMN-G (n=9), and other low-grade/benign non-mucinous lesions demonstrated little reactivity with mAb Das-1. Conversely, cyst fluid from high-risk/malignant IPMNs (n=18) expressed significantly higher reactivity (p0.0001). The sensitivity and specificity of mAbDas-1 in detecting high-risk/malignant IPMNs were 89% and 100%, respectively.mAb Das-1 reacts with high specificity to tissue and cyst fluid from high-risk/malignant IPMNs and thus may help in preoperative clinical risk stratification.

Background. Overexpression of AnnexinA2 (ANXA2) has been reported in several epithelial cancers, including colorectal cancers (CRC) (Cancer Letters, 2007). Increasing expression of gastrin gene, and hence progastrin (PG), has also been reported in CRCs. We recently discovered that ANXA2 serves as a non-conventional receptor for PG (Oncogene, 2007). We additionally reported that binding of PGwith extracellular, membrane associated, ANXA2 results in endocytosis and co-localization of PG/ANXA2 intracellularly (Gastro, 2010), and that ANXA2 is required for mediating mitogenic and anti-apoptotic effects of PG on colon cancer cells. ANXA2 is normally involved with intracellular trafficking. During the course of our studies we discovered that ANXA2 is also present on outer membranes of CRC cells, bound to a 29KDa transmembrane protein, and also released into the medium. To further understand physiological significance of these unexpected findings, we examined if ANXA2 is present in serum of patients positive for colorectal growth and if ANXA2 co-localizes with PG in tumor sections, in relation to disease status. Methods, Results and Conclusions. Secretion of ANXA2 (10-50ng/106 cells) was confirmed in conditioned medium (CM) of CRC cells using quantitative Western Blot assay using standard curve with rhANXA2; nontransformed cells were negative. Serum from CRC tumor bearing mice were positive for ANXA2, while control mice were negative. Next, serum samples were obtained from consented patients at time of endoscopy or as discarded samples from CRC patients on day of surgery, as per our IRB protocols. Serum from patients, negative for colonic growths (Normal, N) had low levels of ANXA2 (

Koushik K. Das, Benjamin Samstein, James V. Guarrera, Milan Kinkhabwala, Lloyd E. Ratner and Jai Radhakrishnan Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, New York, USA and Department of Surgery, Columbia University Medical Center, New York, New York, USA Correspondence: Jai Radhakrishnan, Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, New York, USA. E-mail: kkd2002@columbia.edu