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Rania Shamekh,1,* Marilin Rosa,2,* Zena Sayegh,2 Masoumeh Ghayouri,2 Richard Kim,3 Mokenge P Malafa,3 Domenico Coppola2 1Department of Pathology, University of South Florida, 2Department of Anatomic Pathology, 3Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA *These authors contributed equally to this work Background: Receptor tyrosine-protein kinase erbB-2, which is also frequently called human epidermal growth factor receptor-2 (Her-2) or Her-2/neu, has been found to be overexpressed in various human cancers.Hypothesis: The aim of this pilot study was to explore the frequency of Her-2/neu gene amplification and protein expression in extrahepatic cholangiocarcinoma (EHBC). We used the World Health Organization classification criteria for EHBC.Materials and methods: This was a retrospective study using 88 tissue samples, including 45 samples from non-neoplastic biliary tissue (NNB) and 43 samples of extrahepatic cholangiocarcinoma (EHBC). A tissue microarray including NNB and EHBC was constructed and analyzed by immunohistochemistry (IHC) and dual in situ hybridization for Her-2/neu protein expression and amplification, respectively. The Her-2/neu expression was scored following the guidelines used for the ToGA study.Results: All NNB samples and all but one EHBC samples showed no expression of Her-2/neu by IHC. The one EHBC case immunohistochemically positive for Her-2/neu had an IHC score of 3+. Her-2/neu gene amplification was present in two EHBC samples only and included the case found to be positive by IHC.Conclusion: Our findings are similar to those reported in the literature. Although Her-2/neu overexpression has been documented in many types of cancer, Her-2/neu protein overexpression tends to have no role in the development and/or progression of EHBC. Keywords: extrahepatic, cholangiocarcinoma, Her-2/neu, ToGA, immunohistochemistry

Rania Shamekh,1 Mauro Cives,2 Jaime Mejia,3 Domenico Coppola,4 1Department of Pathology, University of South Florida, 2Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA; 3Department of Pathology, Institutode Patologia Mejia Jimenez, Cali, Colombia; 4Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA Abstract: Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of death worldwide. It accounts for >9% of all cancers. One of the pathogenic factors of CRC is germline mutation, leading to alteration and inactivation in the mismatch repair (MMR) genes. The aim of the study is to compare the frequency of alterations in MMR protein expression in Caucasian CRC patients with Colombian CRC patients. A total of 45 Colombians and 48 Caucasians with CRC were studied. The microsatellite instability status of tumors was determined in primary CRC by immunohistochemistry using the automated Ventana Ultra. The combined loss of MLH1 and PMS2 was the most common alteration in both Colombian (11%, five out of 45) and Caucasian (12%, six out of 48) CRC patients. Interestingly, the loss of PMS2 expression in the presence of intact MLH1 was the second most common alteration in Colombians (8%, four out of 45), which was never seen in the Caucasian cohort (P=0.05). The loss of MLH1 alone and the combined loss of MSH6 and PMS2 expression were only observed in one out of 45 (2%) Colombians but not in Caucasians. The combined loss of MSH2 and MSH6 was not observed in any of the patients studied. The preliminary findings support a significant difference in alterations of MMR protein expression in Colombian CRC patients compared with Caucasian CRC patients. These findings are novel and warrant further studies in larger cohorts. Keywords: colon cancer, MSI, MMR, immunohistochemistry

We present an overview of the radon surveys at Stromboli island starting from the 2002, with the aim to better understand the relation between in-soil radon degassing and change in volcanic activity. Radon measurements were performed by means of different, passive, methodologies. By using a radon network of 21 sampling sites, placed in the NE sector of the island, we effected periodic surveys by means of two manually techniques. Track-etch detectors and EPERM electrets allowed us to construct a continuous time-series of radon measurements during the period 2002–2007 and to recognize the short-time variations. Radon activity shows, by means of EPERM® electrets, a wide range of values, from 0.3 to 50 kBq/m3. These data confirm the role of the local effects on the in-soil radon emissions and show that the structural alignments represent a preferential pathways for the radon migration from soil to air. Prom the 2007 we developed two real-time multiparametric, fully automated stations where the measurements of radon activity, acquired every 15 minutes, are correlated with the soil temperature and atmospheric pressure data. The first results show the important role of the atmospheric factors (e.g. soil temperature) in the acquired radon measurements.

Radon emission from soil at Stromboli Island has been monitored since 2002 utilizing a network of 25 stations and exposing two kinds of detectors: E-PERM and calibrated track-etches (LR115). We present and discuss the data from 2002 to 2007, thus including the last two major eruptive cycles. Earthquake-volcano interactions were detected providing evidence that radon emissions are somehow related to the occurrence of regional earthquakes. Single deep earthquakes related to active subduction, such as Salina event (ML = 5.1) of May 5, 2004, may be capable of increasing the ascent of geothermal fluids due to the passage of seismic waves. In addition, we observed major eruptions at Stromboli were preceded by anomalies that occurred at three summit stations that reached values above 20000 Bq m−3 : this is considered an anomalous value and could be regarded, under particular environmental conditions, as a potential precursory signal of a change in volcanic activity.

Neuroendocrine tumors (NETs) are highly vascular neoplasms overexpressing vascular endothelial growth factor (VEGF) as well as VEGF receptors (VEGFR). Axitinib is a potent, selective inhibitor of VEGFR-1, -2 and -3, currently approved for the treatment of advanced renal cell carcinoma. We performed an open-label, two-stage design, phase II trial of axitinib 5mg twice daily in patients with progressive unresectable/metastatic low-to-intermediate grade carcinoid tumors. The primary end points were progression-free survival (PFS) and 12-month PFS rate. The secondary end points included time to treatment failure (TTF), overall survival (OS), overall radiographic response rate (ORR), biochemical response rate and safety. A total of 30 patients were enrolled and assessable for toxicity; 22 patients were assessable for response. After a median follow-up of 29months, we observed a median PFS of 26.7months (95% CI, 11.4-35.1), with a 12-month PFS rate of 74.5% (±10.2). The median OS was 45.3 months (95% CI, 24.4-45.3), and the median TTF was 9.6months (95% CI, 5.5-12). The best radiographic response was partial response (PR) in 1/30 (3%) and stable disease (SD) in 21/30 patients (70%); 8/30 patients (27%) were unevaluable due to early withdrawal due to toxicity. Hypertension was the most common toxicity that developed in 27 patients (90%). Grade 3/4 hypertension was recorded in 19 patients (63%), leading to treatment discontinuation in six patients (20%). Although axitinib appears to have an inhibitory effect on tumor growth in patients with advanced, progressive carcinoid tumors, the high rate of grade 3/4 hypertension may represent a potential impediment to its use in unselected patients.

Bagana is a remote, highly active volcano, located on Bougainville Island in southeastern Papua New Guinea. The volcano has exhibited sustained and prodigious sulfur dioxide gas emissions in recent decades, accompanied by frequent episodes of lava extrusion. The remote location of Bagana and its persistent activity have made it a valuable case study for satellite observations of active volcanism. This remoteness has also left many features of Bagana relatively unexplored. Here, we present the first measurements of volcanic gas composition, achieved by unoccupied aerial system (UAS) flights through the volcano's summit plume, and a payload comprising a miniaturized MultiGAS. We combine our measurements of the molar CO2/SO2 ratio in the plume with coincident remote sensing measurements (ground‐ and satellite‐based) of SO2 emission rate to compute the first estimate of CO2 flux at Bagana. We report low SO2 and CO2 fluxes at Bagana from our fieldwork in September 2019, ∼320 ± 76 td−1 and ∼320 ± 84 td−1, respectively, which we attribute to the volcano's low level of activity at the time of our visit. We use satellite observations to demonstrate that Bagana's activity and emissions behavior are highly variable and advance the argument that such variability is likely an inherent feature of many volcanoes worldwide and yet is inadequately captured by our extant volcanic gas inventories, which are often biased to sporadic measurements. We argue that there is great value in the use of UAS combined with MultiGAS‐type instruments for remote monitoring of gas emissions from other inaccessible volcanoes. Plain Language Summary: Bagana is a remote and highly active volcano in southeastern Papua New Guinea (PNG). Historically, it has been among the most active volcanoes in PNG, notable for its long‐lived eruptions and sustained gas emissions. Bagana has only been infrequently studied before now. We use unoccupied aerial systems (drones) along with ground‐ and satellite‐based remote sensing data to characterize the chemical composition and flux of Bagana's gas emissions and place these in the context of global volcanic emissions. Owing to low activity during the time of our fieldwork, we report lower than anticipated emissions of carbon dioxide and sulfur dioxide from Bagana. We argue that characterizing highly variable volcanic emissions is challenging without long‐term continuous observations and that, for remote volcanoes like Bagana, both drones and satellite observations are powerful tools to undertake these observations. Key Points: We present the first measurements of volcanic gas composition at Bagana volcanoCO2 and SO2 fluxes at Bagana vary widely with levels of unrest, from ∼102 to ∼104 td−1Unoccupied aerial systems (drones) are of great value in monitoring emissions from inaccessible volcanic summits [ABSTRACT FROM AUTHOR]