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101. The dark age of single organ screening is over: CD24 is a novel universal simple blood test for early detection of cancer.

Author

Shapira, Shiran, primary, Kazanov, Dina, additional, Ben Shimon, Marina, additional, Hay Levy, Mori, additional, Mdah, Fatin, additional, Asido, Shir, additional, Carmel, Narin, additional, Yossepowitch, Ofer, additional, Grisaru, Dan, additional, Fliss, Dan, additional, Isakov, Ofer, additional, Lahat, Guy, additional, Nachmany, Ido, additional, Gluck, Nathan, additional, Peer, Michael, additional, Wolf, Ido, additional, and Arber, Nadir, additional

Published
2020
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102. MON-194 Phaeochromocytoma-Paraganglioma (PPGL): Post-Operative Hypotension Is a Vanishing Phenomenon

Author

Osher, Esther, primary, Tordjman, Karen Michele, primary, Klausner, Joseph, primary, Nachmany, Ido, primary, Sagie, Boaz, primary, Stern, Naftali, primary, Lahat, Guy, primary, Wolf, Ido, primary, Zac, Lilach, primary, Otremski, Sorina, primary, Barnes, Sophie, primary, Aizic, asaf, primary, Zohar, Naomi Even, primary, and Greenman, Yona, primary

Published
2020
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104. Micro-RNA Expression Patterns Predict Metastatic Spread in Solid Pseudopapillary Neoplasms of the Pancreas

Author

Cohen, Shmuel Jaffe, primary, Papoulas, Michail, additional, Graubardt, Nadine, additional, Ovdat, Esther, additional, Loewenstein, Shelly, additional, Kania-Almog, Juliane, additional, Pasmanik-Chor, Metsada, additional, Brazowski, Eli, additional, Cagnano, Emanuela, additional, Nachmany, Ido, additional, Lahat, Guy, additional, Klausner, Joseph M., additional, and Lubezky, Nir, additional

Published
2020
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107. Head-to-head comparison of [68Ga]Ga-FAPI-04 and [18F]-FDG PET/CT in evaluating the extent of disease in gastric adenocarcinoma.

Author

Kuten, Jonathan, Levine, Charles, Shamni, Ofer, Pelles, Sharon, Wolf, Ido, Lahat, Guy, Mishani, Eyal, and Even-Sapir, Einat

Subjects
POSITRON emission tomography computed tomography, GASTRIC diseases, PERITONEAL cancer, ADENOCARCINOMA, STOMACH cancer, STOMACH tumors, PILOT projects, RADIOISOTOPES, RADIOPHARMACEUTICALS, POSITRON emission tomography, DEOXY sugars, COMPUTED tomography
Abstract

Background: [18F]-Fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) may sometimes be suboptimal for imaging gastric adenocarcinoma. The recently introduced [68Ga]Ga-FAPI-04 (FAPI) PET/CT targets tumor stroma and has shown considerable potential in evaluating the extent of disease in a variety of tumors. Methods: We performed a head-to-head prospective comparison of FAPI and FDG PET/CT in the same group of 13 patients with gastric adenocarcinoma who presented for either initial staging (n = 10) or restaging (n = 3) of disease. Lesion detection and maximum standardized uptake value (SUVmax) were compared between the two types of radiotracers. Results: All ten primary gastric tumors were FAPI-positive (100% detection rate), whereas only five were also FDG-positive (50%). SUVmax was not significantly different, but the tumor-to-background ratio was higher for FAPI (mean, median, and range of 4.5, 3.2, and 0.8–9.7 for FDG and 12.9, 11.9, and 2.2–23.9 for FAPI, P = 0.007). The level of detection of regional lymph node involvement was comparable. FAPI showed a superior detection rate for peritoneal carcinomatosis (100% vs. none). Two patients with widespread peritoneal carcinomatosis underwent a follow-up FAPI scan after chemotherapy: one showed partial remission and the other showed progressive disease. Conclusions: The findings of this pilot study suggest that FAPI PET/CT outperforms FDG PET/CT in detecting both primary gastric adenocarcinoma and peritoneal carcinomatosis from gastric cancer. FAPI PET/CT also shows promise for monitoring response to treatment in patients with peritoneal carcinomatosis from gastric cancer; however, larger trials are needed to validate these preliminary findings. [ABSTRACT FROM AUTHOR]

Published
2022
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108. 5‐Hydroxymethylcytosine as a clinical biomarker: Fluorescence‐based assay for high‐throughput epigenetic quantification in human tissues

Author

Margalit Sapir, Avraham Sigal, Shahal Tamar, Michaeli Yael, Gilat Noa, Magod Prerna, Caspi Michal, Loewenstein Shelly, Lahat Guy, Friedmann‐Morvinski Dinorah, Kariv Revital, Rosin‐Arbesfeld Rina, Zirkin Shahar, and Ebenstein Yuval

Abstract

Epigenetic transformations may provide early indicators for cancer and other disease. Specifically, the amount of genomic 5‐hydroxymethylcytosine (5‐hmC) was shown to be globally reduced in a wide range of cancers. The integration of this global biomarker into diagnostic workflows is hampered by the limitations of current 5‐hmC quantification methods. Here we present and validate a fluorescence‐based platform for high‐throughput and cost‐effective quantification of global genomic 5‐hmC levels. We utilized the assay to characterize cancerous tissues based on their 5‐hmC content, and observed a pronounced reduction in 5‐hmC level in various cancer types. We present data for glioblastoma, colorectal cancer, multiple myeloma, chronic lymphocytic leukemia and pancreatic cancer, compared to corresponding controls. Potentially, the technique could also be used to follow response to treatment for personalized treatment selection. We present initial proof‐of‐concept data for treatment of familial adenomatous polyposis.

Published
2019

110. 5‐Hydroxymethylcytosine as a clinical biomarker: Fluorescence‐based assay for high‐throughput epigenetic quantification in human tissues

Author

Margalit, Sapir, primary, Avraham, Sigal, additional, Shahal, Tamar, additional, Michaeli, Yael, additional, Gilat, Noa, additional, Magod, Prerna, additional, Caspi, Michal, additional, Loewenstein, Shelly, additional, Lahat, Guy, additional, Friedmann‐Morvinski, Dinorah, additional, Kariv, Revital, additional, Rosin‐Arbesfeld, Rina, additional, Zirkin, Shahar, additional, and Ebenstein, Yuval, additional

Published
2019
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112. Predicting Survival in Patients Undergoing Resection for Locally Recurrent Retroperitoneal Sarcoma: A Study and Novel Nomogram from TARPSWG

Author

Raut, Chandrajit P., primary, Callegaro, Dario, additional, Miceli, Rosalba, additional, Barretta, Francesco, additional, Rutkowski, Piotr, additional, Blay, Jean-Yves, additional, Lahat, Guy, additional, Strauss, Dirk C., additional, Gonzalez, Ricardo, additional, Ahuja, Nita, additional, Grignani, Giovanni, additional, Quagliuolo, Vittorio, additional, Stoeckle, Eberhard, additional, De Paoli, Antonino, additional, Pillarisetty, Venu G., additional, Nessim, Carolyn, additional, Swallow, Carol J., additional, Bagaria, Sanjay, additional, Canter, Robert, additional, Mullen, John, additional, Gelderblom, Hans J., additional, Pennacchioli, Elisabetta, additional, van Coevorden, Frits, additional, Cardona, Kenneth, additional, Fiore, Marco, additional, Fairweather, Mark, additional, and Gronchi, Alessandro, additional

Published
2019
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114. Pancreatic cancer: Surgery is a feasible therapeutic option for elderly patients

Author

Ben-Haim Menahem, Gerstenhaber Fabian, Nachmany Ido, Lubezky Nir, Sever Ronen, Lahat Guy, Nakache Richard, Koriansky Josef, and Klausner Josef M

Subjects
Surgery, RD1-811, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Compromised physiological reserve, comorbidities, and the natural history of pancreatic cancer may deny pancreatic resection from elderly patients. We evaluated outcomes of elderly patients amenable to pancreatic surgery. Methods The medical records of all patients who underwent pancreatic resection at our institution (1995-2007) were retrospectively reviewed. Patient, tumor, and outcomes characteristics in elderly patients aged ≥ 70 years were compared to a younger cohort ( Results Of 460 patients who had surgery for pancreatic neoplasm, 166 (36%) aged ≥ 70y. Compared to patients < 70y (n = 294), elderly patients had more associated comorbidities; 72% vs. 43% (p = 0.01) and a higher rate of malignant pathologies; 73% vs. 59% (p = 0.002). Operative time and blood products consumption were comparable; however, elderly patients had more post-operative complications (41% vs. 29%; p = 0.01), longer hospital stay (26.2 vs. 19.7 days; p < 0.0001), and a higher incidence of peri-operative mortality (5.4% vs. 1.4%; p = 0.01). Multivariable analysis identified age ≥ 70y as an independent predictor of shorter disease-specific survival (DSS) among patients who had surgery for pancreatic adenocarcinoma (n = 224). Median DSS for patients aged ≥ 70y vs. < 70y were 15 months (SE: 1.6) vs. 20 months (SE: 3.4), respectively (p = 0.05). One, two, and 5-Y DSS rates for the cohort of elderly patients were 58%, 36% and 23%, respectively. Conclusions Properly selected elderly patients can undergo pancreatic resection with acceptable post-operative morbidity and mortality rates. Long term survival is achievable even in the presence of adenocarcinoma and therefore surgery should be seriously considered in these patients.

Published
2011
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117. 5‐Hydroxymethylcytosine as a clinical biomarker: Fluorescence‐based assay for high‐throughput epigenetic quantification in human tissues.

Author

Margalit, Sapir, Avraham, Sigal, Shahal, Tamar, Michaeli, Yael, Gilat, Noa, Magod, Prerna, Caspi, Michal, Loewenstein, Shelly, Lahat, Guy, Friedmann‐Morvinski, Dinorah, Kariv, Revital, Rosin‐Arbesfeld, Rina, Zirkin, Shahar, and Ebenstein, Yuval

Subjects
ADENOMATOUS polyposis coli, CHRONIC lymphocytic leukemia, COLON cancer, PANCREATIC cancer, PATIENT selection, DESMOID tumors
Abstract

Epigenetic transformations may provide early indicators for cancer and other disease. Specifically, the amount of genomic 5‐hydroxymethylcytosine (5‐hmC) was shown to be globally reduced in a wide range of cancers. The integration of this global biomarker into diagnostic workflows is hampered by the limitations of current 5‐hmC quantification methods. Here we present and validate a fluorescence‐based platform for high‐throughput and cost‐effective quantification of global genomic 5‐hmC levels. We utilized the assay to characterize cancerous tissues based on their 5‐hmC content, and observed a pronounced reduction in 5‐hmC level in various cancer types. We present data for glioblastoma, colorectal cancer, multiple myeloma, chronic lymphocytic leukemia and pancreatic cancer, compared to corresponding controls. Potentially, the technique could also be used to follow response to treatment for personalized treatment selection. We present initial proof‐of‐concept data for treatment of familial adenomatous polyposis. What's new? The amount of genomic 5‐hydroxymethylcytosine (5‐hmC) was shown to be globally reduced in a wide range of cancerous tissues. The utility of such an epigenetic transformation as a clinical biomarker is hampered by the limitations of existing detection assays, however. The authors present a simple‐to‐perform fluorescence‐based platform for high‐throughput and cost‐effective quantification of global genomic 5‐hmC levels. They demonstrate the assay's sensitivity in detecting various cancers and its applicability for colorectal cancer diagnosis. Potentially, the technique could also be used to follow response to treatment for personalized treatment selection, with the authors providing initial proof‐of‐concept data for familial adenomatous polyposis. [ABSTRACT FROM AUTHOR]

Published
2020
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128. Optimization of liposomal indocyanine green for imaging of the urinary pathways and a proof of concept in a pig model.

Author

Friedman-Levi, Yael, Larush, Liraz, Diana, Michele, Marchegiani, Francesco, Marescaux, Jacques, Goder, Noam, Lahat, Guy, Klausner, Joseph, Eyal, Sara, Magdassi, Shlomo, and Nizri, Eran

Subjects
ANIMAL models in research, URETER injuries, LAPAROSCOPIC surgery, DIAGNOSTIC imaging, INDOCYANINE green, THERAPEUTICS, ANIMAL experimentation, COMPARATIVE studies, RESEARCH methodology, MEDICAL cooperation, ARTIFICIAL membranes, MICE, NEAR infrared spectroscopy, RESEARCH, RESEARCH funding, SWINE, URETERS, EVALUATION research, INDOLE compounds, FLUORESCENT dyes
Abstract

Background: Iatrogenic ureteral injury is an increasing concern in the laparoscopic era, affecting both patient morbidity and costs. Current techniques enabling intraoperative ureteral identification require invasive procedures or radiations. Our aim was to develop a real-time, non-invasive, radiation-free method to visualize ureters, based on near-infrared (NIR) imaging. For this purpose, we interfered with the biliary excretion pathway of the indocyanine green (ICG) fluorophore by loading it into liposomes, enabling renal excretion. In this work, we studied various parameters influencing ureteral imaging.Methods: Fluorescence intensity (FI) of various liposomal ICG sizes and doses were characterized in vitro and subsequently tested in vivo in mice and pigs. Quantification was performed by measuring FI in multiple points and applying the ureteral/retroperitoneum ratio (U/R).Results: The optimal liposomal ICG loading dose was 20%, for the different liposomes' sizes tested (30, 60, 100 nm). Higher concentration of ICG decreased FI. In vivo, the optimal liposome size for ureteral imaging was 60 nm, which yielded a U/R of 5.2 ± 1.7 (p < 0.001 vs. free ICG). The optimal ICG dose was 8 mg/kg (U/R = 2.1 ± 0.4, p < 0.05 vs. 4 mg/kg). Only urine after liposomal ICG injection had a measurable FI, and not after free ICG injection. Using a NIR-optimized laparoscopic camera, ureters could be effectively imaged in pigs, from 10 min after injection and persisting for at least 90 min. Ureteral peristaltic waves could be clearly identified only after liposomal ICG injection.Conclusions: Optimization of liposomal ICG allowed to visualize enhanced ureters in animal models and seems a promising fluorophore engineering, which calls for further developments. [ABSTRACT FROM AUTHOR]

Published
2018
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129. T-Helper 1 Immune Response in Metastatic Lymph Nodes of Pancreatic Ductal Adenocarcinoma: A Marker For Prolonged Survival.

Author

Nizri, Eran, Sternbach, Neta, Bar-David, Shoshi, Ben-Yehuda, Amir, Gerstenhaber, Fabian, Ofir, Tali, Wolf, Ido, Weiner, Gilad, Lahat, Guy, and Klausner, Joseph

Abstract

Background: Although lymph node (LN) metastases is considered a grave prognostic sign in pancreatic ductal adenocarcinoma (PDAC), patients with positive lymph nodes (PLN) constitute a heterogeneous group. Our purpose was to identify morphological and immune parameters in the primary tumor and in PLN of resected PDAC patients, which could further stratify these patients to different subgroups. Methods: We retrospectively evaluated histological and immunohistochemical characteristics of 66 patients with PDAC who were operated at our institution. These were subsequently correlated to clinical outcome. Results: Mean patient age and number of LN harvested was 65.5 ± 10.3 and 12.3 ± 6.5 years, respectively. Tumor size (T stage) and perineural invasion had no effect on clinical outcome. High-grade tumor was associated with decreased survival [overall survival (OS) = 19.6 ± 2.7 months for poorly differentiated PDAC vs. 31.2 ± 4 for well and moderately differentiated, p = 0.03]. Patients with ≥ 8 PLN had significantly worse outcome (OS = 7.3 ± 0.8 months for PLN ≥ 8 vs. OS = 30.1 ± 3.2 months for PLN < 8, p < 0.0001). T helper (Th) 1 immune response was measured both by its effector cells (CD8) and expression of its main transcription factor, T-bet. CD8 high patients had significantly increased OS compared with CD8 low (OS = 36.8 ± 5.3 months for CD8 + high vs. OS = 24.3 ± 3.5 for CD8 + low, p = 0.03) Similarly, Th1 predominant immune response measured by T-bet expression was associated with improved OS compared with non-Th1 (OS = 32.8 ± 3.2 vs. OS = 19.5 ± 2.9, p < 0.0001). Conclusions: Our data indicate an association between Th1-type immune response and increased survival. Future research is needed to exploit Th1 immune response as a biological marker for immunotherapy. [ABSTRACT FROM AUTHOR]

Published
2018
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130. Converting a Sleeve Gastrectomy to a Gastric Bypass for Weight Loss Failure-Is It Worth It?

Author

Nevo, Nadav, Abu-Abeid, Subhi, Lahat, Guy, Klausner, Joseph, and Eldar, Shai M.

Subjects
GASTRECTOMY, GASTRIC bypass, WEIGHT loss, TREATMENT effectiveness, BODY mass index, PATIENTS
Abstract

Background: Sleeve gastrectomy (SG) is gaining popularity and has become the procedure of choice for many bariatric surgeons. Long-term weight loss failure is not uncommon. The preferred revisional procedure for these patients is still under debate. Objective: The objective of this study was to assess the safety and efficacy of laparoscopic gastric bypass as a revisional surgery for sleeve gastrectomy patients with weight loss failure. Setting: The study was done at a bariatric surgery center in a university hospital. Methods: We reviewed our prospectively collected database and identified all patients who underwent conversion of a sleeve gastrectomy to a gastric bypass for weight loss failure. Data on patient demographics, baseline characteristics, and outcomes of bariatric surgery were retrieved. Results: Twenty-three patients with a mean body mass index (BMI) of 41.6 kg/m2 (range 34.1-50.1 kg/m2) underwent conversion to a gastric bypass. Four patients underwent a gastric band prior to the sleeve gastrectomy, and two patients underwent a re-sleeve gastrectomy prior to conversion to a gastric bypass. At a mean follow-up of 24 months (range 9-46 months), the average body mass index (BMI) decreased to 33.8 kg/m2 and the excess body mass index loss (EBMIL) was 42.6%. Diabetes, hypertension, dyslipidemia, and obstructive sleep apnea resolved or improved in 44.4, 45.5, 50, and 50% of the patients, respectively. Three patients developed early postop complications (13%), while late complications occurred in four patients (17%). Conclusion: Converting a sleeve gastrectomy to a gastric bypass for weight loss failure is safe, yet weight loss benefit is limited. [ABSTRACT FROM AUTHOR]

Published
2018
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133. Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma

Author

Koch Institute for Integrative Cancer Research at MIT, Jacks, Tyler E., Kirsch, David G., Mukherjee, Sayan, Lev, Dina, Brigman, Brian E., Yoon, Sam S., Hornicek, Francis J., Eward, William C., Stangenberg, Lars, Dodd, Rebecca D., Lazar, Alexander J., Lahat, Guy, Dodd, Leslie, Riedel, Richard F., Mito, Jeffrey K., Jacks, Tyler E, Koch Institute for Integrative Cancer Research at MIT, Jacks, Tyler E., Kirsch, David G., Mukherjee, Sayan, Lev, Dina, Brigman, Brian E., Yoon, Sam S., Hornicek, Francis J., Eward, William C., Stangenberg, Lars, Dodd, Rebecca D., Lazar, Alexander J., Lahat, Guy, Dodd, Leslie, Riedel, Richard F., Mito, Jeffrey K., and Jacks, Tyler E

Abstract

Undifferentiated pleomorphic sarcoma/Malignant Fibrous Histiocytoma (MFH) is one of the most common subtypes of human soft tissue sarcoma. Using cross species genomic analysis, we define a geneset from the LSL-Kras[superscript G12D]; Trp53[superscript Flox/Flox] mouse model of soft tissue sarcoma that is highly enriched in human MFH. With this mouse geneset as a filter, we identify expression of the RAS target FOXM1 in human MFH. Expression of Foxm1 is elevated in mouse sarcomas that metastasize to the lung and tissue microarray analysis of human MFH correlates overexpression of FOXM1 with metastasis. These results suggest that genomic alterations present in human MFH are conserved in the LSL-Kras[superscript G12D]; p53[superscript Flox/Flox] mouse model of soft tissue sarcoma and demonstrate the utility of this pre-clinical model.

Published
2010

134. Angiosarcoma

Author

Rao, Priya, primary, Lahat, Guy, additional, Arnold, Christina, additional, Gavino, Alde Carlo, additional, Lahat, Sharon, additional, Hornick, Jason L., additional, Lev, Dina, additional, and Lazar, Alexander J., additional

Published
2013
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135. Long-Term Outcomes in Patients with Radiation-Associated Angiosarcomas of the Breast Following Surgery and Radiotherapy for Breast Cancer

Author

Torres, Keila E., primary, Ravi, Vinod, additional, Kin, Katherine, additional, Yi, Min, additional, Guadagnolo, B. Ashleigh, additional, May, Caitlin D., additional, Arun, Banu K., additional, Hunt, Kelly K., additional, Lam, Ryan, additional, Lahat, Guy, additional, Hoffman, Aviad, additional, Cormier, Janice N., additional, Feig, Barry W., additional, Lazar, Alexander J., additional, Lev, Dina, additional, and Pollock, Raphael E., additional

Published
2012
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139. Activated MET Is a Molecular Prognosticator and Potential Therapeutic Target for Malignant Peripheral Nerve Sheath Tumors

Author

Torres, Keila E., primary, Zhu, Quan-Sheng, additional, Bill, Katelynn, additional, Lopez, Gonzalo, additional, Ghadimi, Markus P., additional, Xie, Xianbiao, additional, Young, Eric D., additional, Liu, Juehui, additional, Nguyen, Theresa, additional, Bolshakov, Svetlana, additional, Belousov, Roman, additional, Wang, Suizhau, additional, Lahat, Guy, additional, Liu, Jun, additional, Hernandez, Belinda, additional, Lazar, Alexander J., additional, and Lev, Dina, additional

Published
2011
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140. Epithelioid Sarcoma and Unclassified Sarcoma with Epithelioid Features: Clinicopathological Variables, Molecular Markers, and a New Experimental Model

Author

Sakharpe, Aniket, primary, Lahat, Guy, additional, Gulamhusein, Taher, additional, Liu, Ping, additional, Bolshakov, Svetlana, additional, Nguyen, Theresa, additional, Zhang, Pingyu, additional, Belousov, Roman, additional, Young, Eric, additional, Xie, Xianbiao, additional, Rao, Priya, additional, Hornick, Jason L., additional, Lazar, Alexander J., additional, Pollock, Raphael E., additional, and Lev, Dina, additional

Published
2011
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142. Angiosarcoma

Author

Lahat, Guy, primary, Dhuka, Asha R., additional, Hallevi, Hen, additional, Xiao, Lianchun, additional, Zou, Changye, additional, Smith, Kerrington D., additional, Phung, Thuy L., additional, Pollock, Raphael E., additional, Benjamin, Robert, additional, Hunt, Kelly K., additional, Lazar, Alexander J., additional, and Lev, Dina, additional

Published
2010
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150. IFN Regulatory Factor 8 Sensitizes Soft Tissue Sarcoma Cells to Death Receptor–Initiated Apoptosis via Repression of FLICE-like Protein Expression

Author

Yang, Dafeng, primary, Wang, Suizhao, additional, Brooks, Craig, additional, Dong, Zheng, additional, Schoenlein, Patricia V., additional, Kumar, Vijay, additional, Ouyang, Xinshou, additional, Xiong, Huabao, additional, Lahat, Guy, additional, Hayes-Jordan, Andrea, additional, Lazar, Alexander, additional, Pollock, Raphael, additional, Lev, Dina, additional, and Liu, Kebin, additional

Published
2009
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