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The safety and efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal metastasis in palliative settings remain poorly investigated and understood. Chemotherapy-refractory patients often present with symptomatic disease. This study investigated the safety and survival outcomes of optimal CRS/HIPEC performed primarily for palliation.Palliative CRS/HIPEC was defined as asymptomatic patients who did not respond to three or more lines of chemotherapy, progression on current chemotherapy, and/or any symptomatic disease progression, including ascites, bowel obstruction, and pain. Data collected included demographics, histology, length of stay (LOS), perioperative complications, perioperative mortality, adjuvant chemotherapy use, peritoneal recurrence, overall recurrence, and overall survival.The median number of lines of chemotherapy received prior to CRS/HIPEC was 3.2, and 81% of patients were symptomatic. There were no postoperative deaths and the major complication rate was 22%. Ostomy creation and abdominal wall reconstruction were performed in 24% and 21% of patients, respectively. The median LOS was 11 days and successful palliation was achieved in 97% of patients. Overall survival was 13.5 months and factors associated with prolonged survival included optimal CRS (R1/R2a; p 0.01) and the use of adjuvant chemotherapy (p 0.001). Synchronous liver metastasis in the colon cancer subset did not negatively impact survival.CRS/HIPEC was performed safely in the palliative setting in patients with symptomatic progressive disease receiving multiple lines of chemotherapy. Median survival exceeded 1 year and factors associated with longer survival were optimal CRS and adjuvant chemotherapy. Liver metastasis did not preclude survival benefit in colon cancer patients. CRS/HIPEC can be considered for palliation but should be performed at high-volume centers.

Pancreatic cancer is a highly lethal malignancy. Lack of early diagnostic markers makes timely detection of pancreatic cancer a highly challenging endeavor. Exosomes have emerged as information-rich cancer specific biomarkers. However, characterization of tumor-specific exosomes has been challenging. This study investigated the proof of principle that exosomes could be used for the detection of pancreatic cancer. Label-free analysis of exosomes purified from normal and pancreatic cancer cell lines was performed using surface enhanced Raman Spectroscopy (SERS) and principal component differential function analysis (PC-DFA), to identify tumor-specific spectral signatures. This method differentiated exosomes originating from pancreatic cancer or normal pancreatic epithelial cell lines with 90% accuracy. The cell line trained PC-DFA algorithm was next applied to SERS spectra of serum-purified exosomes. This method exhibited up to 87% and 90% predictive accuracy for HC and EPC individual samples, respectively. Overall, our study identified utility of SERS spectral signature for deciphering exosomal surface signature.

In the frame of the design and development of Liquid breeder blankets, a number of R & D activities are in progress in the area of liquid metal technology development. In presence of strong plasma confining toroidal magnetic field, motion of electrically conducting liquid metal leads to Magneto Hydro Dynamic (MHD) phenomena, as a consequence of which liquid metal flow profile changes inside the flow channels of liquid breeder blankets and additional pressure drop occurs due to the flow opposing Lorentz force (J × B). For the design and development of liquid breeder blankets, 3D MHD flow needs to be studied for various flow configurations as present in the liquid breeder blankets. A lead lithium (Pb-Li) MHD loop is being developed at IPR to perform MHD experiments for Pb-Li flow in various flow geometry such as U-bend, transition zones, circular pipes, sudden expansion and contraction, etc. The test mock ups will be placed in a uniform magnetic field up to 1.4 T, produced by a C-shaped Iron core electromagnet with a pole gap of 370 mm. Both Isothermal and thermo-fluid MHD experiments are being planned for MHD database generation and code validation.

Background and objectives Outcomes for gastrointestinal peritoneal metastases (GI-PM) are worse compared to systemic metastases, with a paucity of data exploring extended mutation profiling. An exploratory mutation analysis in GI-PMs was performed as a "proof of concept" of potential predictive values of profiling in GI-PM and rates of actionable mutations. Methods The study included 40 GI-PM patients: 14 low-grade mucinous carcinoma peritonei and 26 HG-PM (12 colons, 10 appendix, 4 small bowels). Demographics, histologies, peritoneal cancer indexes, cytoreduction scores, and survival data were collected. NGS 50-gene mutation profiling was performed on 38 specimens. The association of mutations with survival was evaluated in high-grade PM. Results KRAS, TP53, and SMAD4 mutations were observed in 61%, 29%, and 8% of cases across all tumor histologies. In 66% cases >1 mutations occurred, associated with decreased survival in HG-PM: 32 vs 73 months, P = .03. TP53 or SMAD4 mutations were associated with decreased survival in HG-PM: 22 vs 48 months, P = .02. Actionable mutations were detected in 70%. Conclusion Actionable mutations were detected at high rates. GI-PMs have similar mutational profiles and TP53, SMAD4, and/or >1 mutation were associate with decreased survival in HG-PM. This data supports the concept of the extended mutation profiling utility in GI-PM warranting further investigation.

The eutectic Pb-Li alloy has been chosen as a candidate material for the liquid breeder blanket, as it offers a unique combination of tritium breeding neutron absorbing and neutron multiplying capabilities. In fusion blanket, molten Pb-Li moves under plasma confining toroidal magnetic field, producing an induced electric current inside the liquid metal due to the interaction of the moving fluid with the magnetic field. The coupling of induced electric current and magnetic field generates a Lorentz force opposite to the flow direction, and this in turn, modifies the flow profile. The experimental and numerical flow studies of liquid Pb-Li under transverse magnetic field are of great importance, as it directly impacts the blanket performance. A liquid Lead Lithium MHD loop is being developed at Institute for Plasma Research (IPR), Gujarat, India for isothermal and thermo-fluid MHD studies in blanket relevant flow geometries such as sudden expansion/contraction, coupled channels and multiple bends. A test mockup with rectangular flow cross-section and having bends perpendicular to the magnetic field has been fabricated. A 3D MHD flow analysis has been performed numerically for the test mock up at a magnetic field of 1.4T (Hartmann number of order of 1500). The fabrication details of test mockup and the results of the Pb-Li flow analysis are presented and discussed. The flow field and pressure distribution in the presence and absence of the magnetic field are also compared. The existence of recirculation zones and their redistribution in the presence of magnetic field are discussed.

The incidence of venous thromboembolism (VTE) in peritoneal malignancies can approach 30 to 50 per cent without prophylaxis. Prophylaxis in cytoreductive surgeries (CRS) presents a challenge to preoperative heparin-based therapy because of an increased risk of coagulopathy and potential for bleeding. Herein, we report the large series of CRS and hyperthermic intraperitoneal chemotherapy receiving dextran-40 prophylaxis. Retrospective chart review of peritoneal malignancies patients undergoing CRS at University of Nebraska Medical Center identified 69 individuals who received dextran-40 between 2010 and 2013. The incidences of VTEs, perioperative bleeding, complications, morbidity, and mortality were determined in-hospital and at 90 days. Of the 69 patients treated, the 30-day VTE rate was 8.7 per cent, and no pulmonary embolisms, bleeding, anaphylactoid reaction, or mortality were observed with dextran usage. The specific VTE events included three upper extremity and three lower extremity VTEs. No additional VTE events were identified between 30 and 90 days. In conclusion, dextran-40 prophylaxis was not associated with any perioperative bleeding events, and the observed incidence of VTE was comparable to reported heparin-based prophylaxis in CRS/hyperthermic intraperitoneal chemotherapy patients. This data supports further exploration of dextran-40 as a VTE prophylactic agent in complex surgical oncology cases.

Development of biomarkers that detect early stage resectable premalignant lesions of colon can provide critical aid in the prevention of colorectal cancer. Recent lines of evidence suggest the utility of mucin expression to predict malignant transformation of colon pre-neoplastic lesions. In this study, we investigated the combined expression of multiple mucins and mucin-associated glycans during the adenoma-carcinoma sequence of colon cancer progression. Further, we evaluated their applicability as markers for differentiating adenomas/adenocarcinomas from hyperplastic polyps. Immunohistochemical analyses performed on colon disease tissue microarrays revealed downregulation of MUC2 and MUC4 expression (p

The global cancer burden (GCB) is expected to rise significantly during the next few decades with most of the new cancers and cancer-related deaths afflicting the low- to middle-income countries. The ability to tackle this rising GCB requires the presence of an adequately trained surgical oncology workforce, which is dependent on credible training pathways and sustainable certification pipelines. The purpose of this article is to review briefly the training patterns and certification requirements for surgical oncologists globally by sampling representative countries across all regions of the world. A thorough literature search was conducted using multiple websites of credible national/global organizations as well as the websites of individual countries. Countries from select regions in the world were included (based on the World Health Organization regions and Human Development Index) in the analysis to determine the prevalent trends in the training of surgical oncologists globally. Several trends and significant differences were noted in the training patterns of surgical oncologists globally. The presence or absence of domestic surgical oncology fellowships had an inverse correlation to the income level of the country. Countries without domestic fellowships usually relied on high-income foreign destinations for their training. The results of the analysis demonstrated significant variability in training of surgical oncologists globally. Despite the diversity, we noticed some general trends based on which some recommendations were put forth for increasing the global surgical oncology workforce.

Several benchmark problems recommended by the fusion community have been analysed using the ANSYS FLUENT magnetohydrodynamic (MHD) code and the results have been compared with available literature data. The selected problems are: (i) 2D fully developed laminar steady MHD flow inside the electrically insulating square duct, (ii) 3D laminar steady developing MHD flow in a non-uniform magnetic field and (iii) natural convection transient MHD flow. Fairly good agreement has been found between the simulation and reported results. The FLUENT has been found to be capable of predicting 3D MHD effects, which arise in the presence of the transverse fringing magnetic field. The natural convection phenomena under the uniform constant magnetic field have also been successfully captured by the code.

Currently, rates of referral of patients with peritoneal metastasis in the United States who qualify for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are low, in part because of the misperception of high morbidity and mortality rates. However, patients requiring major gastrointestinal surgical procedures with similar complication rates are routinely referred.To evaluate the relative safety of CRS/HIPEC.Retrospective cohort study of 34 114 patients who underwent CRS/HIPEC, right lobe hepatectomy, trisegmental hepatectomy, pancreaticoduodenectomy, and esophagectomy between January 1, 2005, and December 31, 2015, included in the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) database. Data analysis was performed in 2018.Data from the NSQIP database were used to compare perioperative and 30-day postoperative morbidity and mortality rates of CRS/HIPEC (1822 patients) with other, well-accepted, high-risk surgical oncology procedures: right lobe hepatectomy (5109 patients), trisegmental hepatectomy (2449 patients), pancreaticoduodenectomy (Whipple) (16 793 patients), and esophagectomy (7941 patients).For 34 114 patients, median (interquartile range [IQR]) age was 63 (55-71) years and 42% were female. Patients undergoing CRS/HIPEC tended to be younger, with a median age of 57 years, and esophagectomy had the highest median (IQR) American Society of Anesthesiologists classification (3 [3-3]). When compared with CRS/HIPEC, higher complication rates were reported in the following categories: (1) superficial incisional infection in Whipple and esophagectomy (5.4% [95% CI, 4.4%-6.4%] vs 9.7% [95% CI, 9.3%-10.1%] and 7.2% [95% CI, 6.6%-7.8%], respectively; P .001); (2) deep incisional infection in Whipple (1.7% [95% CI, 1.1%-2.3%] vs 2.7% [95% CI, 2.5%-2.9%]; P .01); (3) organ space infection in right lobe hepatectomy (7.2% [95% CI, 6.0%-8.4%] vs 9.0% [95% CI, 8.2%-9.8%]; P = .02), trisegmental hepatectomy (12.4% [95% CI, 11.1%-13.7%]; P .001), and Whipple (12.9% [95% CI, 12.4%-13.4%]; P .001); and (4) return to the operating room for esophagectomy (6.8% [95% CI, 5.6%-8.0%] vs 14.4% [95% CI, 13.6%-15.2%]; P .001). Median (IQR) length of hospital stay was lower in CRS/HIPEC (8 [5-11] days) than Whipple (10 [7-15] days) and esophagectomy (10 [8-16] days) (P .001). Overall 30-day mortality was lower in CRS/HIPEC (1.1%; 95% CI, 0.6%-1.6%) compared with Whipple (2.5%; 95% CI, 2.3%-2.7%), right lobe hepatectomy (2.9%; 95% CI, 2.4%-3.4%), esophagectomy (3.0%; 95% CI, 2.6%-3.4%), and trisegmental hepatectomy (3.9%; 95% CI, 3.1%-4.7%) (P .001).Comparative analysis revealed CRS/HIPEC to be safe, often safer across the spectrum of NSQIP safety metrics when compared with similar-risk oncologic procedures. Patient selection was important in achieving observed outcomes. High complication rates are a misperception from early CRS/HIPEC experience and should no longer deter referral of patients to experienced centers or impede clinical trial development in the United States.

Worldwide there were 337,872 new cases of pancreatic cancer diagnosed in 2012 with 330,372 deaths and a prevalence rate of 211,544 [1, 2] (Table 1). The incidence, mortality and prevalence rates are higher in males when compared to females worldwide. The number of newly diagnosed cases varies very widely between countries of low versus high incidence. The incidence of pancreatic cancer is low in India when compared to the United States (U.S). Except for the incidence rate in females, India falls into the lowest quintile in terms of incidence (males), mortality (males and females) and prevalence (males and females). In contrast, the United States falls into the top most quintile for incidence, mortality and prevalence of pancreatic cancer in both sexes [1, 2]. Table 1 Incidence, mortality, and prevalence of pancreatic cancer [1–6] Pancreatic cancer is the fourth leading cause of cancer-related deaths in both males and females in the United States, only to be surpassed by cancers involving the lung/bronchus, breast, prostate, and colon/rectum [3]. Pancreatic cancer accounts for nearly 7 % of all cancer-related deaths in the United States [3]. Pancreatic cancer also stands 9th in the number of estimated new cancer cases diagnosed in females in 2014, accounting for 3 % of all new malignancies [3]. In contrast, a review of the 12 population based cancer registries (PBCRs) from India (Benaguluru, Barshi, Bhopal, Chennai, Delhi, Mumbai, Ahmedabad, Karunagappally, Kolkata, Nagpur, Pune and Thiruvananthapuram) demonstrates that the incidence of pancreatic cancer is significantly lower than in the U.S [4, 5]. Although the incidence in India is presently lower than that of the U.S, the rate of rise in new cases of pancreatic cancer in the future will be much higher in India [6]. It is estimated that by 2035 the number of new cases will increase by nearly 89 % in India when compared to 55 % in the US [6]. Although surgical resection offers the only hope of prolonging survival, few patients (15–20 %) present at a stage that is suitable for operative intervention. Of the patients that present with resectable disease, not everyone undergoes operative resection, either due to poor performance status or failure to access care at a tertiary care center with the required expertise. The mortality rates associated with pancreatic surgery have improved significantly since the early 1970’s due to a combination of various factors such as improved surgical techniques, better anesthesia and critical care management, concentration of care at tertiary care centers, and improved ability to deal with life-threatening complications. Although the mortality rates have improved, the morbidity associated with pancreatic resections is still considerable up to 50 %. The article by Penumadu et al. provides a review of how to prevent and treat adverse outcomes related to haemorrhage, pancreatic fistula, delayed gastric emptying and bile leaks. The improved mortality rates and ability to address adverse events has prompted some groups to advocate for more aggressive resections that go beyond that standard pancreaticoduodenectomy. The article by Schoellhammer et al. discusses the issues related to extended lymphadenectomy and vascular resections with reconstructions. Several advances have been made over the past few decades in the management of pancreatic cancer. Although most of these have been relevant to the actual treatment, we have also seen advances in imaging and definitions and staging. The historical bi-categories of resectable and unresectable have been further subdivided into resectable, borderline resectable, locally advanced, and unresectable. The article by Mullapudi and Hawkes et al. discusses the definitions and management of the newer entity called borderline resectable pancreatic cancer. The other advances made in pancreatic surgery include the introduction of minimally invasive surgical techniques with laparoscopy and robotic surgery. Pancreatic surgery remained the last bastion to the advances of minimally invasive surgery. An increasing number of centers across the world are performing laparoscopic/robotic pancreatic resections and have reported comparable outcomes in highly selected patients. The article by Senthilinathan et al. provides a comparison between open and laparoscopic pancreatic resections and document that in centers with available expertise the outcomes are similar. We have come a long way from the era of 5-fluorouracil which since its discovery in the 1950’s had remained the mainstay for chemotherapy for gastrointestinal cancers, including pancreatic cancer till the introduction of gemcitabine. The role of chemotherapy has changed in numerous aspects such as: a) timing of administration with increasing emphasis on pre-operative administration, b) different types of combination regimes such as FOLFIRINOX and c) different combination approaches with radiation therapy. Although studies in the U.S have shown the benefit of combining radiation with chemotherapy, this has not been duplicated in European studies. The article by Sirohi et al. provides a review of the current drugs and combinations available to treat patients with pancreatic cancer in all settings. Lastly, the diagnosis of pancreatic cancer can still be problematic even in the era of triple phase imaging and endoscopic capabilities. This can become even more difficult in patients with chronic pancreatitis or in patients from areas where tuberculosis is endemic. The article by Dhar et al. outlines the approach to treat patients with a history of chronic pancreatitis and likely diagnosis of pancreatic cancer. We have witnessed several advances in the management of pancreatic cancer with improved short-term outcomes. While the short-term outcomes have improved, the long-term outcomes continue to remain dismal except for a select group of patients that receive their care at centers of excellence. We may be close to the peak of surgical excellence as witnessed by the remarkably low mortality rates following resections. Further advances may arrive with the increasing use of minimally invasive and robotic techniques. What is more pressing and needed to swing the pendulum of survival favorably is a better understanding of the biology of the disease. This can help in identifying risk factors, target high risk individual for early diagnosis and define therapeutic targets for developing newer drugs. This is paramount so that it can equip physicians with the tools required to tackle this lethal disease. Finally, all efforts should be placed on maintaining the quality of life in these patients regardless of the treatment intent or stage of disease. This combination of treatment advances and a focus on quality of life should be the preferred approach for treating patients diagnosed with this lethal malignancy.

// Shiv Ram Krishn 1 , Sukhwinder Kaur 1 , Yuri M. Sheinin 2 , Lynette M. Smith 3 , Shailendra K. Gautam 1 , Asish Patel 4 , Maneesh Jain 1 , Vasthala Juvvigunta 5 , Priya Pai 1 , Audrey J. Lazenby 2 , Hemant K. Roy 7 and Surinder K. Batra 1,2,6 1 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA 2 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA 3 Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska, USA 4 Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA 5 Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA 6 Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA 7 Department of Gastroenterology, Boston Medical Center, Boston, Massachusetts, USA Correspondence to: Surinder K. Batra, email: // Sukhwinder Kaur, email: // Keywords : mucins, hyperplastic polyps, sessile serrated adenoma/polyps, tubular adenomas, O-glycans Received : August 12, 2016 Accepted : September 20, 2016 Published : September 29, 2016 Abstract Sessile serrated adenoma/polyps (SSA/P) are premalignant lesions of colorectal cancer that are difficult to distinguish histologically from hyperplastic polyps (HP) of minimal to no malignant potential. Specific markers for differentiating SSA/P from HP can aid clinicians for optimizing colon surveillance intervals. The present study investigates the potential of mucins and associated O-glycans to distinguish SSA/P from HP. Expression of colonic mucins (MUC1, MUC4, MUC17, MUC2, and MUC5AC) and O-glycans [Sialyl Lewis A (CA19-9) and Tn/Sialyl-Tn on MUC1] were analyzed in HP ( n =33), SSA/P ( n =39), and tubular adenoma (TA) ( n =36) samples by immunohistochemistry. A significantly reduced expression of MUC4 ( p =0.0066), elevated expression of MUC17 ( p =0.0002), and MUC5AC ( p

Pancreatic cancer (PC) is a lethal malignancy that lacks specific diagnostic markers. The present study explores the diagnostic potential of the most differentially overexpressed secretory mucin MUC5AC alone and in combination with CA19-9 using multi-center training and validation sets.The expression of MUC5AC in benign pancreatic pathologies, PC precursor lesions, primary PC tissues and metastatic lesions was evaluated by immunohistochemistry. Circulating MUC5AC levels were measured using sandwich ELISA assay developed in-house, and CA19-9 was measured using radioimmunoassay. A combined training set (n=346) was used to evaluate the diagnostic (n=241) and predictive (n=105, total samples 201 from pre- and post-surgical and chemotherapy set) significance of MUC5AC. Results were further validated with a pre-defined cut-off value using independent sets from the Mayo Clinic (n=94) and the University of Pittsburgh Medical Center (n=321).Tissue expression analyses indicated the de novo expression of MUC5AC in pancreatic intraepithelial precursor lesions 1A (PanIN1A); the expression was maintained through all stages of progression to invasive adenocarcinoma. The median circulating MUC5AC levels in patients with resectable early-stage PC (EPC) (stage 1/2; 67.2 ng/ml, IQR: 23.9-382.1) and unresectable late-stage PC (LPC) (stage 3/4; 389.7 ng/ml, IQR: 87.7-948.6) were significantly higher compared with (P-value ≤0.0001) benign controls (BC) (7.2 ng/ml, IQR: 0.4-26.5) and (P-value ≤0.0001) chronic pancreatitis (CP) controls (8.4 ng/ml, IQR: 1.5-19.2). In the diagnostic training set (n=241), MUC5AC efficiently differentiated EPC from healthy controls (HC) (83%/80% sensitive (SN)/specific (SP)), BC (67%/87% SN/SP), and CP (83%/77% SN/SP). Independent validation sets from the Mayo Clinic and UPMC confirmed the diagnostic potential of MUC5AC to differentiate EPC from BC (68%/73%; 65%/83%) and CP (68%/79%; 65%/72%). Furthermore, MUC5AC and CA19-9 combination significantly improved (p-value0.001) the diagnostic accuracy for differentiating resectable cases from controls.MUC5AC is a valuable diagnostic biomarker, either alone or in combination with CA19-9, to differentiate PC from CP and benign controls.

Borderline resectable pancreatic cancer (BRPC) is an evolving diagnostic entity that blurs the distinction between resectable and locally advanced pancreatic cancer (Varadhachary et al. Ann Surg Oncol 13:1035–1046, 2006). Until recently the management of this disease has been poorly defined; however, consensus guidelines have been developed regarding the proper management of this diagnostic entity. Recent studies have shown that if appropriately identified and treated, this subset of disease can have outcomes similar to pancreatic cancer that is defined as resectable (Laurence et al. J Gastrointest Surg 15:2059–2069, 2011). The aim of this review is to outline the current consensus on definitions, workup and management of BRPC, and also provide a summary of issues that require progress as defined by the International Study Group of Pancreatic Surgery (ISGPS).

Alternative gene splicing, occurring ubiquitously in multicellular organisms can produce several protein isoforms with putatively different functions. The enormously extended genomic structure of mucin genes characterized by the presence of multiple exons encoding various domains may result in functionally diverse repertoire of mucin proteins due to alternative splicing. Splice variants (Svs) and mutations in mucin genes have been observed in various cancers and shown to participate in cancer progression and metastasis. Although several mucin Svs have been identified, their potential functions remain largely unexplored with the exception of the Svs of MUC1 and MUC4. A few studies have examined the expression of MUC1 and MUC4 Svs in cancer and indicated their potential involvement in promoting cancer cell proliferation, invasion, migration, angiogenesis and inflammation. Herein we review the current understanding of mucin Svs in cancer and inflammation and discuss the potential impact of splicing in generating a functionally diverse repertoire of mucin gene products. We also performed mutational analysis of mucin genes across five major cancer types in International Cancer Genome Consortium database and found unequal mutational rates across the panel of cancer-associated mucins. Although the functional role of mucins in the pathobiology of various malignancies and their utility as diagnostic and therapeutic targets remain undisputed, these attributes need to be reevaluated in light of the potentially unique functions of disease-specific genetic variants of mucins. Thus, the expressional and functional characterization of the genetic variants of mucins may provide avenues to fully exploit their potential as novel biomarkers and therapeutic targets.

e18102Background: VTE rates in cytoreductive surgery (CRS) for peritoneal metastasis (PM) without prophylaxis are high, 30-50%. Many factors in this population promote VTE events including tumor bu...

222 Background: Pancreatic juice remains an underutilized resource for diagnosing pancreatic cancer. Mucins are high molecular weight glycoproteins differentially upregulated in pancreatic cancer, and we hypothesize that their profile in pancreatic juice may have diagnostic potential. Methods: Pancreatic juice was obtained during endoscopy from non-healthy non-pancreatic control (NHPC, n = 57), chronic pancreatitis (CP, n = 23), and pancreatic cancer (PC, n = 23) patients. Sandwich ELISA was used to detect MUC1, MUC4, MUC5AC, CA125, and CA19-9. Kruskal-Wallis test and Wilcoxon rank sum test for group and pairwise comparison was done with p < 0.05 as significant. Logistic regression with ROC curve modeling of log transformed data was done for each biomarker individually and in combination to determine odds ratio (OR), sensitivity (SN), and specificity (SP) for PC. Results: PC vs NHPC: MUC5AC had the best individual performance for diagnosing PC with an OR = 2.78 (95% CI = 1.51-5.13), AUC = 0.81, and optimal SN/SP of 0.83 and 0.67, respectively. CA125 was increased in PC with an OR = 2.31 (95% CI = 1.4-4.0), AUC = 0.73, and optimal SN/SP of 0.88 and 0.67. CA19-9 was increased in PC with an OR = 1.5 (95% CI = 1.2-1.8), AUC = 0.76, and optimal SN/SP of 0.73 and 0.70. A combination of MUC1, MUC5AC, CA125, and CA19-9 outperformed all individual markers and had the largest AUC (0.89) with optimal SN/SP of 0.84 and 0.79. PC vs CP: MUC1 concentration in PC was significantly less than CP with an OR = 0.21 (95%CI = 0.088-0.49), AUC = 0.82, and optimal SN/SP of 0.87 and 0.78. PC vs NHPC+CP: MUC1 was decreased significantly in PC with an OR = 0.65 (95% CI = 0.44-0.96), AUC = 0.69, and optimal SN/SP of 0.87 and 0.63. CA125 was increased in PC with an OR = 1.64 (95%CI = 1.1-2.4), AUC = 0.66, and optimal SN/SP of 0.67 and 0.64. CA19-9 was increased in PC with an OR = 1.32 (95%CI = 1.1-1.6), AUC = 0.68, and optimal SN/SP of 0.63 and 0.67. A combination of MUC1, MUC5AC, CA125, and CA19-9 had an AUC = 0.86 with optimal SN/SP of 0.87 and 0.77 for PC. Conclusions: MUC1, MUC5AC, CA125, and CA19-9 combination provides a significantly improved diagnostic panel compared to any individual marker in pancreatic juice for detecting malignancy.

In this article a novel way of synchronizing two parallel connected sparkgap switches with accuracies of 1–5 ns for high frequency pulsed power applications is described. The circuit design of a synchronized sparkgap switch circuit is discussed. The circuit uses a combination of one master sparkgap and a set of inductor and capacitors to synchronize two sparkgaps and can be controlled via an IGBT switch. Critical issues for circuit design are presented together with analytical calculations and simulations. Experimental verification of the novel topology is carried out in a prototype experimental setup. Results showing nanosecond level of accuracy in synchronization are reported in this paper along with simulations and analysis.

e22030 Background: Peritoneal metastasis (PM) presents with relative frequency in gastrointestinal malignancies (GIM). Patients with PM are challenging due to frequent symptoms, refractory response...

Previous studies in atrial cardiomyocytes isolated from various mammalian species have demonstrated poorly developed transverse(t)-tubules and inhomogeneities of sarcoplasmic reticulum (SR) Ca2+ release, but little is known of mice. Here, we examined the t-tubular organization and action potential-evoked Ca2+ release in in situ myocytes, using confocal microscopy of Langendorff-perfused hearts. Imaging of ANNINE-6plus-stained sarcolemmal membranes revealed paucity of t-tubules in atrial, but densely and regularly spaced t-tubules in ventricular myocytes. However, both myocyte types exhibited regular, striated appearance of type 2 ryanodine receptor distribution. Line-scans (2 ms/line) across multiple myocytes obtained during sinus rhythm from fluo-4 loaded hearts revealed homogeneous [Ca2+]i increases in ventricular myocytes, whereas atrial myocytes exhibited areas with delayed transients (see Figure). Histograms of F50values (the time to 50% of peak F/F0 [where F indicates fluorescence intensity, and F0 indicates F at rest]) for the subsarcolemmal (SS) and central (C) compartments in ventricular myocytes were largely congruent, whereas the corresponding atrial histograms did not superimpose and exhibited multiple peaks. Thus, major myocyte-to-myocyte differences in the spatial organization of SR Ca2+ release exist among in situ mouse atrial myocytes, likely reflecting non-uniform t-tubule distribution.View Large Image | View Hi-Res Image | Download PowerPoint Slide

Background Disseminated peritoneal adenomucinosis (DPAM) patients often have a history of appendectomy with identification of an incidental mucinous neoplasm (low-grade appendiceal mucinous neoplasm (LAMN)). The rate of developing DPAM is not well established. Methods Twenty-two patients with incidental LAMN were identified and monitored with cancer markers and CT every 4–6 months. Laparoscopy with peritoneal washing was performed in patients either in the event of radiographic disease or after 12 months in absence of radiographic disease. The rate of detecting peritoneal metastasis was determined for CT scan and laparoscopy. Results Peritoneal metastasis was detected in 5 (23 %) patients. Occult disease was detected in four patients at laparoscopy without a detectable disease on CT scan. One patient developed radiographic progression at 6 months confirmed with laparoscopy. Four patients were treated with cytoreductive surgery (CRS)/HIPEC and one with CRS only. The 17 patients with negative laparoscopy remain disease free with a median follow-up of 50 months. Conclusions The rate of peritoneal metastasis in incidental LAMN patients was 23 %. Laparoscopy was the primary screening tool identifying occult metastasis. The median PCI of 7 was low, and all the patients underwent R0/R1 resections. This study revealed 1 in every 4.4 patients with LAMN may develop PMP. Longer follow-up and further patient surveillance is warranted.