548 results on '"Wolfgang CL"'
Search Results
2. Algorithm-based care versus usual care for the early recognition and management of complications after pancreatic resection in the Netherlands: an open-label, nationwide, stepped-wedge cluster-randomised trial
- Author
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Smits, F Jasmijn, primary, Henry, Anne Claire, additional, Besselink, Marc G, additional, Busch, Olivier R, additional, van Eijck, Casper H, additional, Arntz, Mark, additional, Bollen, Thomas L, additional, van Delden, Otto M, additional, van den Heuvel, Daniel, additional, van der Leij, Christiaan, additional, van Lienden, Krijn P, additional, Moelker, Adriaan, additional, Bonsing, Bert A, additional, Borel Rinkes, Inne H, additional, Bosscha, Koop, additional, van Dam, Ronald M, additional, Derksen, Wouter J M, additional, den Dulk, Marcel, additional, Festen, Sebastiaan, additional, Groot Koerkamp, Bas, additional, de Haas, Robbert J, additional, Hagendoorn, Jeroen, additional, van der Harst, Erwin, additional, de Hingh, Ignace H, additional, Kazemier, Geert, additional, van der Kolk, Marion, additional, Liem, Mike, additional, Lips, Daan J, additional, Luyer, Misha D, additional, de Meijer, Vincent E, additional, Mieog, J Sven, additional, Nieuwenhuijs, Vincent B, additional, Patijn, Gijs A, additional, te Riele, Wouter W, additional, Roos, Daphne, additional, Schreinemakers, Jennifer M, additional, Stommel, Martijn W J, additional, Wit, Fennie, additional, Zonderhuis, Babs A, additional, Daamen, Lois A, additional, van Werkhoven, C Henri, additional, Molenaar, I Quintus, additional, van Santvoort, Hjalmar C, additional, Blomjous, JG, additional, de Boer, MT, additional, van den Boezem, P, additional, Bouwense, S, additional, Bruijnen, R, additional, Buis, CI, additional, del Chiaro, M, additional, Coene, PP, additional, Coolsen, M, additional, Daams, F, additional, Dejong, K, additional, Draaisma, W, additional, Eker, HH, additional, Elsen, AH, additional, Gerhards, MF, additional, Hartog, H, additional, Hoogwater, FJ, additional, Imani, F, additional, Jenniskens, S, additional, de Jong, KP, additional, Karsten, TM, additional, Klaase, JM, additional, de Kleine, RHJ, additional, van Laarhoven, CJ, additional, van der Lelij, H, additional, Manusama, ER, additional, Meerdink, M, additional, Meijerink, M, additional, Nederend, J, additional, Nijkamp, MW, additional, Nota, CL, additional, Porte, RJ, additional, Reef, J, additional, de Reuver, P, additional, van Rijswijk, C, additional, Romkens, T, additional, Rupert, C, additional, van der Schelling, GP, additional, Serafino, JP, additional, Vos, LD, additional, Vriens, MR, additional, Beers-Vural, E, additional, Wagtenberg, JM, additional, Wijsman, JH, additional, de Wilde, RF, additional, Wolfgang, CL, additional, and Zeh, HJ, additional
- Published
- 2022
- Full Text
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3. CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan
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Vennin, C, Melenec, P, Rouet, R, Nobis, M, Cazet, As, Murphy, Kj, Herrmann, D, Reed, Da, Lucas, Mc, Warren, Sc, Elgundi, Z, Pinese, M, Kalna, G, Roden, D, Samuel, M, Zaratzian, A, Grey, St, Da Silva, A, Leung, W, Mathivanan, S, Wang, Yx, Braithwaite, Aw, Christ, D, Benda, A, Parkin, A, Phillips, Pa, Whitelock, Jm, Gill, Aj, Sansom, Oj, Croucher, Dr, Parker, Bl, Pajic, M, Morton, Jp, Cox, Tr, Timpson, P, Johns, Al, Chantrill, La, Chou, A, Steinmann, A, Arshi, M, Dwarte, T, Froio, D, Pereira, B, Ritchie, S, Chambers, Cr, Metcalf, X, Waddell, N, Pearson, Jv, Patch, Am, Nones, K, Newell, F, Mukhopadhyay, P, Addala, V, Kazakoff, S, Holmes, O, Leonard, C, Wood, S, Grimmond, Sm, Hofmann, O, Christ, A, Bruxner, T, Samra, Js, Pavlakis, N, High, Ha, Asghari, R, Merrett, Nd, Pavey, D, Das, A, Cosman, Ph, Ismail, K, O'Connnor, C, Stoita, A, Williams, D, Spigellman, A, Lam, Vw, Mcleod, D, Kirk, J, Kench, Jg, Grimison, P, Cooper, Cl, Sandroussi, C, Goodwin, A, Mead, Rs, Tucker, K, Andrews, L, Texler, M, Forest, C, Epari, Kp, Ballal, M, Fletcher, Dr, Mukhedkar, S, Zeps, N, Beilin, M, Feeney, K, Nguyen, Nq, Ruszkiewicz, Ar, Worthley, C, Chen, J, Brooke-Smith, Me, Papangelis, V, Clouston, Ad, Barbour, Ap, O'Rourke, Tj, Fawcett, Jw, Slater, K, Hatzifotis, M, Hodgkinson, P, Nikfarjam, M, Eshleman, Jr, Hruban, Rh, Wolfgang, Cl, Lawlor, Rt, Beghelli, S, Corbo, V, Scardoni, M, Bassi, C, Biankin, Av, Dixon, J, Jamieson, Nb, and Chang, Dk
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0301 basic medicine ,medicine.medical_treatment ,Drug Resistance ,General Physics and Astronomy ,02 engineering and technology ,Mice ,Cancer-Associated Fibroblasts ,Cell Movement ,lcsh:Science ,Inbred BALB C ,Cancer ,education.field_of_study ,Mice, Inbred BALB C ,Multidisciplinary ,Tumor ,021001 nanoscience & nanotechnology ,3. Good health ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,0210 nano-technology ,Pancreas ,Signal Transduction ,Cancer microenvironment ,Cell biology ,Science ,Population ,Perlecan ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell Line ,03 medical and health sciences ,Pancreatic cancer ,Cell Line, Tumor ,medicine ,Humans ,Animals ,Neoplasm Invasiveness ,education ,Cell Proliferation ,Neoplastic ,fungi ,General Chemistry ,Immunotherapy ,medicine.disease ,Pancreatic Neoplasms ,030104 developmental biology ,Gene Expression Regulation ,Drug Resistance, Neoplasm ,Cancer cell ,Cancer research ,biology.protein ,Neoplasm ,lcsh:Q ,Stromal Cells ,Tumor Suppressor Protein p53 ,Heparan Sulfate Proteoglycans - Abstract
Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote and restrain disease progression. Here, we interrogate how cancer cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence of a p53-driven hierarchy, where cancer cells with a gain-of-function (GOF) mutant p53 educate a dominant population of CAFs that establish a pro-metastatic environment for GOF and null p53 cancer cells alike. We also demonstrate that CAFs educated by null p53 cancer cells may be reprogrammed by either GOF mutant p53 cells or their CAFs. We identify perlecan as a key component of this pro-metastatic environment. Using intravital imaging, we observe that these dominant CAFs delay cancer cell response to chemotherapy. Lastly, we reveal that depleting perlecan in the stroma combined with chemotherapy prolongs mouse survival, supporting it as a potential target for anti-stromal therapies in pancreatic cancer., Subtypes of cancer associated fibroblasts can both promote and suppress tumorigenesis. Here, the authors investigate how p53 status in pancreatic cancer cells affects their interaction with cancer associated fibroblasts, and report perlecan as a mediator of the pro-metastatic environment.
- Published
- 2019
4. Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract Recommendations of Verona Consensus Meeting
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Adsay, V, Mino-Kenudson, M, Furukawa, T, Basturk, O, Zamboni, G, Marchegiani, G, Bassi, C, Salvia, R, Malleo, G, Paiella, S, Wolfgang, Cl, Matthaei, H, Offerhaus, Gj, Adham, M, Bruno, Mj, Reid, Md, Krasinskas, A, Klöppel, G, Ohike, N, Tajiri, T, Jang, Kt, Roa, Jc, Allen, P, Fernández-del Castillo, C, Jang, Jy, Klimstra, Ds, Hruban, Rh, Members of Verona Consensus Meeting, 2013, Other departments, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, and Gastroenterology & Hepatology
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robotic ,medicine.medical_specialty ,Intraductal ,Papillary ,Bile Duct Neoplasm ,030230 surgery ,Medical Records ,Article ,laparoscopic ,Branch Duct ,03 medical and health sciences ,0302 clinical medicine ,anatomical resection ,Journal Article ,Humans ,Medicine ,colorectal liver metastasis ,donor hepatectomy ,hepatocellular carcinoma ,liver resection ,pneumoperitoneum ,Mucinous ,Stage (cooking) ,Pancreas ,Frozen section procedure ,business.industry ,Carcinoma in situ ,General surgery ,IPMN ,medicine.disease ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Bile Duct Neoplasms ,Practice Guideline ,Dysplasia ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Neoplasm ,Surgery ,Forms and Records Control ,business ,Carcinoma in Situ - Abstract
Background: There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs). Design: An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. Results: (1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term "minimally invasive" should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; ≤0.5, >0.5-≤1, >1 cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6) The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intrabiliary/cholecystic). Conclusions: These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms.
- Published
- 2016
5. The number of positive nodes accurately predicts recurrence after pancreatoduodenectomy for nonfunctioning neuroendcorne neoplasms
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Andreasi, V, Partelli, S, Javed, Aa, He, J, Muffatti, F, Weiss, Mj, Giannone, F, Sessa, F, La Rosa, S, Doglioni, C, Zamboni, G, Wolfgang, Cl, and Falconi, M
- Published
- 2018
6. The prognosis of colorectal cancer liver metastases associated with inflammatory bowel disease: An exploratory analysis
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Margonis, GA, Buttner, Stefan, Andreatos, N, Wagner, D, Sasaki, K, Galjart, Boris, Kamphues, C, Pawlik, TM, Poultsides, G, Kaczirek, K, Lonning, PE, Verhoef, Kees, Kreis, ME, Wolfgang, CL, Weiss, MJ, and Surgery
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SDG 3 - Good Health and Well-being - Published
- 2018
7. Impact Total Psoas Volume on Short- and Long-Term Outcomes in Patients Undergoing Curative Resection for Pancreatic Adenocarcinoma: a New Tool to Assess Sarcopenia (vol 19, pg 1593, 2015)
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Amini, N, Spolverato, G, Gupta, R, Margonis, Ga, Kim, Y, Wagner, D, Rezaee, N, Weiss, Mj, Wolfgang, Cl, Makary, Mm, Kamel, Ir, and Pawlik, Tm
- Published
- 2016
8. Impact of Sarcopenia on Short- and Long-Term Outcomes in Patients Undergoing Curative Intent Resection for Pancreatic Adenocarcinoma: A New Tool
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Amini, N, Gupta, R, Margonis, Ga, Kim, Y, Spolverato, G, Rezaee, N, Weiss, Mj, Wolfgang, Cl, Makary, Ma, Kamel, Ir, and Pawlik, Tm
- Published
- 2015
9. Defining Incidence and Risk Factors of Venous Thromboembolism after Hepatectomy
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Ejaz, A, Spolverato, G, Kim, Y, Lucas, Dl, Lau, B, Weiss, M, Johnston, Fm, Kheng, M, Hirose, K, Wolfgang, Cl, Haut, E, and Pawlik, Tm
- Published
- 2014
10. RON is not a prognostic marker for resectable pancreatic cancer
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Tactacan, Carole M, Chang, David K, Cowley, Mark J, Humphrey, Emily S, Jianmin, Wu, Gill, Anthony J, Chou, Angela, Nones, Katia, Grimmond, Sean M, Sutherland, Robert L, Biankin, Andrew V, Daly, Roger J, Biankin, Av, Johns, Al, Mawson, A, Chang, Dk, Scarlett, Cj, Brancato, Ma, Rowe, Sj, Simpson, Sl, Martyn-Smith, M, Chantrill, La, Chin, Vt, Chou, A, Cowley, Mj, Caplan, W, Humphris, Jl, Jones, Md, Mead, R, Nagrial, Am, Pajic, M, Pettit, J, Pinese, M, Rooman, I, Wu, Jun, Daly, Rj, Musgrove, Ea, Sutherland, Rl, Grimmond, Sm, Waddell, N, Kassahn, Ks, Miller, Dk, Wilson, Pj, Patch, Am, Song, S, Harliwong, I, Idrisoglu, S, Nourse, C, Nourbakhsh, E, Manning, S, Wani, S, Gongora, M, Anderson, Michela, Holmes, O, Leonard, C, Taylor, D, Wood, JOHN STEPHAN, Xu, C, Nones, K, Fink, Julika, Christ, A, Bruxner, T, Cloonan, N, Newell, F, Pearson, Jv, Samra, Js, Gill, Aj, Nickpavlakis, Guminski, A, Toon, C, Asghari, R, Merrett, Nd, Pavey, Da, Das, A, Cosman, Ph, Ismail, K, O'Connor, C, Lam, Vw, Mcleod, D, Pleass, Hc, James, V, Kench, Jg, Cooper, Cl, Joseph, D, Sandroussi, C, Crawford, M, Texler, M, Forrest, C, Laycock, A, Epari, Kp, Ballal, M, Fletcher, Dr, Mukhedkar, S, Spry, Na, Deboer, B, Chai, M, Feeney, K, Zeps, N, Beilin, M, Nguyen, Nq, Ruszkiewicz, Ar, Worthley, C, Tan, Cp, Debrencini, T, Chen, J, Brooke-Smith, Me, Papangelis, V, Tang, H, Barbour, Ap, Clouston, Ad, Martin, P, O'Rourke, Tj, Chiang, A, Fawcett, Jw, Slater, K, Yeung, S, Hatzifotis, M, Hodgkinson, P, Christophi, C, Nikfarjam, M, Eshleman, Jr, Hruban, Rh, Maitra, A, Iacobuzio-Donahue, Ca, Schulick, Rd, Wolfgang, Cl, Morgan, Ra, Scarpa, A, Lawlor, Rt, Beghelli, S, Corbo, V, Scardoni, M, Bassi, C, Tempero, Ma., and Basic (bio-) Medical Sciences
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Oncology ,Male ,Receptor Protein-Tyrosine Kinases/analysis ,Cancer Research ,Receptor tyrosine kinase ,Kaplan-Meier Estimate ,Surgical oncology ,80 and over ,Prospective cohort study ,Pancreatic Neoplasms/metabolism ,Biomarker ,Gemcitabine ,Chemotherapy ,Adenocarcinoma ,Adult ,Aged ,Aged, 80 and over ,Biomarkers, Tumor ,Blotting, Western ,Female ,Humans ,Immunohistochemistry ,Middle Aged ,Pancreatic Neoplasms ,Prognosis ,Proportional Hazards Models ,Receptor Protein-Tyrosine Kinases ,Tissue Array Analysis ,Tumor ,Blotting ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Adenocarcinoma/metabolism ,CA19-9 ,Western ,Research Article ,medicine.drug ,medicine.medical_specialty ,lcsh:RC254-282 ,Biomarkers, Tumor/analysis ,Breast cancer ,Internal medicine ,Pancreatic cancer ,medicine ,Genetics ,business.industry ,Cancer ,medicine.disease ,business ,aged, 80 and over ,Biomarkers - Abstract
Background The receptor tyrosine kinase RON exhibits increased expression during pancreatic cancer progression and promotes migration, invasion and gemcitabine resistance of pancreatic cancer cells in experimental models. However, the prognostic significance of RON expression in pancreatic cancer is unknown. Methods RON expression was characterized in several large cohorts, including a prospective study, totaling 492 pancreatic cancer patients and relationships with patient outcome and clinico-pathologic variables were assessed. Results RON expression was associated with outcome in a training set, but this was not recapitulated in the validation set, nor was there any association with therapeutic responsiveness in the validation set or the prospective study. Conclusions Although RON is implicated in pancreatic cancer progression in experimental models, and may constitute a therapeutic target, RON expression is not associated with prognosis or therapeutic responsiveness in resected pancreatic cancer.
- Published
- 2012
11. Acinar cell carcinoma of the pancreas: computed tomography features--a study of 15 patients.
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Raman SP, Hruban RH, Cameron JL, Wolfgang CL, Kawamoto S, Fishman EK, Raman, Siva P, Hruban, Ralph H, Cameron, John L, Wolfgang, Christopher L, Kawamoto, Satomi, and Fishman, Elliot K
- Abstract
Objective: Evaluation of the imaging features of pathology-proven acinar cell carcinomas (ACCs) of the pancreas using computed tomography (CT).Methods: We reviewed the CT features, clinical presentations, and clinical outcomes of 15 patients (9 men, 6 women, mean age 62.3) with pathology-proven pancreatic ACCs. An abdominal radiologist retrospectively evaluated each patient's initial imaging study with respect to the lesion's size, location, attenuation (Hounsfield units) on arterial and venous phase images, peripancreatic lymphadenopathy, and distant metastases. Additional parameters studied included biliary and pancreatic ductal dilatation, intratumoral hemorrhage, calcification, the presence of cystic/necrotic components, and whether the tumor was intraparenchymal or exophytic.Results: The ACCs in this series were evenly distributed between the head/uncinate and the tail, were predominantly exophytic (73%), tended to be large (average size 5.1 cm), and were mostly hypodense to the surrounding pancreas on both the arterial and venous phase images. A sizeable proportion demonstrated a cystic or necrotic component (53%) and/or an enhancing capsule (53%). Of those lesions in the head or uncinate process, very few resulted in pancreatic (28%) or biliary (14%) ductal dilatation. None of the lesions in this series showed internal calcification or intratumoral hemorrhage.Conclusion: While a prospective diagnosis is difficult, ACCs have several features which can differentiate them from ductal adenocarcinoma, including their large size, lack of biliary or pancreatic ductal dilatation, exophytic nature, and the presence of an enhancing capsule. [ABSTRACT FROM AUTHOR]- Published
- 2013
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12. EUS-guided tattooing before laparoscopic distal pancreatic resection (with video)
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Lennon AM, Newman N, Makary MA, Edil BH, Shin EJ, Khashab MA, Hruban RH, Wolfgang CL, Schulick RD, Giday S, and Canto MI
- Abstract
Background: Precise localization of small pancreatic tumors during laparoscopic distal pancreatectomy (LDP) can be difficult because of decreased tactile ability of laparoscopy and the homogeneous appearance of the pancreas and surrounding retroperitoneal fat. Precise localization of the lesion is critical to achieving adequate margins of resection and preserving healthy pancreatic tissue. EUS-guided fine-needle tattooing (EUS-FNT) of a pancreatic lesion before LDP has been described in single case reports, but no large series have reported its effectiveness in patients undergoing LDP. Objective: To assess the feasibility, safety, and efficacy of EUS-FNT in consecutive patients undergoing LDP. Design: Retrospective cohort study. Setting: Tertiary-care referral hospital. Patients: This study involved 30 consecutive patients who underwent LDP from 2008 to 2010. Thirteen had EUS-FNT followed by LDP, and 17 had LDP alone. Interventions: LDP or EUS-FNT with a sterile carbon-particle tattoo followed by LDP. Main Outcome Measurements: The following features were examined: the technical success and complication rates of EUS-FNT, visibility of the tattoo at the time of laparoscopy, durability of the tattoo, and pathologic absence of tumor at the resection margin. Results: The final pathology of pancreatic lesions of patients who had EUS-FNT was similar to those who had LDP alone. The median resected tumor size was significantly larger for the LDP-alone patients (median 4.0 cm vs 1.3 cm; P = .03). Thirty-one percent (4/13) of lesions in the EUS-FNT group were not visualized by prior preoperative pancreatic protocol CT. EUS-FNT was feasible in all 13 patients at laparoscopy, with R0 resection and negative final pathology margins in all cases. The tattoo was visible in all 13 EUS-FNT cases, with mean time from EUS-FNT to surgery of 20.3 days (range, 3-69 days). There were no significant complications associated with EUS-FNT. Limitations: Small, retrospective, single-center study. Conclusions: Preoperative EUS-FNT of lesions was technically feasible and safe, and it assisted in the localization of lesions in patients before LDP. The carbon particle tattoo was durable and visible in all cases. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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13. Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital.
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Herman JM, Swartz MJ, Hsu CC, Winter J, Pawlik TM, Sugar E, Robinson R, Laheru DA, Jaffee E, Hruban RH, Campbell KA, Wolfgang CL, Asrari F, Donehower R, Hidalgo M, Diaz LA Jr., Yeo C, Cameron JL, Schulick RD, and Abrams R
- Published
- 2008
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14. A Novel Glutamyl (Aspartyl)-Specific Aminopeptidase A from Lactobacillus delbrueckii with Promising Properties for Application.
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Timo Stressler, Jacob Ewert, Michael Merz, Joshua Funk, Wolfgang Claaßen, Sabine Lutz-Wahl, Herbert Schmidt, Andreas Kuhn, and Lutz Fischer
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Medicine ,Science - Abstract
Lactic acid bacteria (LAB) are auxotrophic for a number of amino acids. Thus, LAB have one of the strongest proteolytic systems to acquit their amino acid requirements. One of the intracellular exopeptidases present in LAB is the glutamyl (aspartyl) specific aminopeptidase (PepA; EC 3.4.11.7). Most of the PepA enzymes characterized yet, belonged to Lactococcus lactis sp., but no PepA from a Lactobacillus sp. has been characterized so far. In this study, we cloned a putative pepA gene from Lb. delbrueckii ssp. lactis DSM 20072 and characterized it after purification. For comparison, we also cloned, purified and characterized PepA from Lc. lactis ssp. lactis DSM 20481. Due to the low homology between both enzymes (30%), differences between the biochemical characteristics were very likely. This was confirmed, for example, by the more acidic optimum pH value of 6.0 for Lb-PepA compared to pH 8.0 for Lc-PepA. In addition, although the optimum temperature is quite similar for both enzymes (Lb-PepA: 60°C; Lc-PepA: 65°C), the temperature stability after three days, 20°C below the optimum temperature, was higher for Lb-PepA (60% residual activity) than for Lc-PepA (2% residual activity). EDTA inhibited both enzymes and the strongest activation was found for CoCl2, indicating that both enzymes are metallopeptidases. In contrast to Lc-PepA, disulfide bond-reducing agents such as dithiothreitol did not inhibit Lb-PepA. Finally, Lb-PepA was not product-inhibited by L-Glu, whereas Lc-PepA showed an inhibition.
- Published
- 2016
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15. Patient readmission and mortality after colorectal surgery for colon cancer: impact of length of stay relative to other clinical factors.
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Schneider EB, Hyder O, Brooke BS, Efron J, Cameron JL, Edil BH, Schulick RD, Choti MA, Wolfgang CL, and Pawlik TM
- Published
- 2012
16. Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers
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Gloria M. Petersen, Ammar A. Javed, Alison P. Klein, Matthew J. Weiss, Janine Ptak, Nickolas Papadopoulos, Ralph H. Hruban, Peter Gibbs, Peter J. Allen, Martin A. Makary, Marco Dal Molin, Jin He, Cristian Tomasetti, Yuxuan Wang, Natalie Silliman, Lisa Dobbyn, Lu Li, Christopher L. Wolfgang, Jeanne Tie, Christopher J. Thoburn, Bert Vogelstein, Fay Wong, Claudio Doglioni, Kenneth W. Kinzler, Michele T. Yip-Schneider, Randall E. Brand, Maria Popoli, Massimo Falconi, Aatur D. Singhi, Samir M. Hanash, Mark A. Schattner, Anirban Maitra, Seung-Mo Hong, Joshua D. Cohen, Joy Schaefer, Michael Goggins, C. Max Schmidt, Song Cheol Kim, Nita Ahuja, Anne Marie Lennon, Cohen, Jd, Javed, Aa, Thoburn, C, Wong, F, Tie, J, Gibbs, P, Schmidt, Cm, Yip-Schneider, Mt, Allen, Pj, Schattner, M, Brand, Re, Singhi, Ad, Petersen, Gm, Hong, Sm, Kim, Sc, Falconi, M, Doglioni, C, Weiss, Mj, Ahuja, N, He, J, Makary, Ma, Maitra, A, Hanash, Sm, Dal Molin, M, Wang, Y, Li, L, Ptak, J, Dobbyn, L, Schaefer, J, Silliman, N, Popoli, M, Goggins, Mg, Hruban, Rh, Wolfgang, Cl, Klein, Ap, Tomasetti, C, Papadopoulos, N, Kinzler, Kw, Vogelstein, B, and Lennon, Am
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Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Pathology ,CA-19-9 Antigen ,Biology ,Gene mutation ,medicine.disease_cause ,Circulating Tumor DNA ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,0302 clinical medicine ,Pancreatic cancer ,Internal medicine ,medicine ,Carcinoma ,Humans ,Liquid biopsy ,Aged ,Multidisciplinary ,Liquid Biopsy ,Cancer ,Middle Aged ,Biological Sciences ,Genes, p53 ,medicine.disease ,Primary tumor ,Pancreatic Neoplasms ,030104 developmental biology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Female ,KRAS ,Carcinoma, Pancreatic Ductal - Abstract
The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests for KRAS gene mutations with carefully thresholded protein biomarkers to determine whether the combination of these markers was superior to any single marker. The cohort tested included 221 patients with resectable pancreatic ductal adenocarcinomas and 182 control patients without known cancer. KRAS mutations were detected in the plasma of 66 patients (30%), and every mutation found in the plasma was identical to that subsequently found in the patient's primary tumor (100% concordance). The use of KRAS in conjunction with four thresholded protein biomarkers increased the sensitivity to 64%. Only one of the 182 plasma samples from the control cohort was positive for any of the DNA or protein biomarkers (99.5% specificity). This combinatorial approach may prove useful for the earlier detection of many cancer types.
- Published
- 2017
17. A Risk Model to Predict 90-Day Mortality among Patients Undergoing Hepatic Resection
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Luca Aldrighetti, Omar Hyder, Amin Firoozmand, Timothy M. Pawlik, Michael A. Choti, Christopher L. Wolfgang, Carlo Pulitano, Rebecca M. Dodson, Hyder, O, Pulitano, C, Firoozmand, A, Dodson, R, Wolfgang, Cl, Choti, Ma, Aldrighetti, L, and Pawlik, Tm
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Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Risk Assessment ,Gastroenterology ,Article ,Age Distribution ,Risk Factors ,Cause of Death ,Internal medicine ,Odds Ratio ,medicine ,Hepatectomy ,Humans ,Postoperative Period ,Sex Distribution ,Survival rate ,Aged ,Retrospective Studies ,Cause of death ,Framingham Risk Score ,Maryland ,business.industry ,Liver Diseases ,Retrospective cohort study ,Odds ratio ,Perioperative ,Middle Aged ,Prognosis ,Surgery ,Survival Rate ,Italy ,Female ,business ,Complication - Abstract
BACKGROUND: Reliable criteria to predict mortality after hepatectomy remain poorly defined. We sought to identify factors associated with 90-day mortality, as well as validate the "50-50" and peak bilirubin of >7 mg/dL prediction rules for mortality after liver resection. In addition, we propose a novel integer-based score for 90-day mortality using a large cohort of patients. STUDY DESIGN: Data from 2,056 patients who underwent liver resection at 2 major hepatobiliary centers between 1990 and 2011 were identified. Perioperative laboratory data, as well as surgical and postoperative details, were analyzed to identify factors associated with liver-related 90-day death. RESULTS: Indications for liver resection included colorectal metastasis (39%), hepatocellular carcinoma (19%), benign mass (17%), or noncolorectal metastasis (14%). Most patients had normal underlying liver parenchyma (71%) and resection involved >= 3 segments (36%). Overall morbidity and mortality were 19% and 2%, respectively. Only 1 patient fulfilled the 50-50 criteria; this patient survived and was discharged on day 8. Twenty patients had a peak bilirubin concentration >7 mg/dL and 5 died within 90 days; the sensitivity and specificity of the > 7-mg/dL rule were 25% and 99.3%, respectively, but overall accuracy was poor (area under the curve 0.574). Factors associated with 90-day mortality included international normalized ratio (odds ratio = 11.87), bilirubin (odds ratio = 1.16), and serum creatinine (odds ratio = 1.87) on postoperative day 3, as well as grade of postoperative complications (odds ratio = 5.08; all p < 0.05). Integer values were assigned to each factor to develop a model that predicted 90-day mortality (area under the curve 0.89). A score of >= 11 points had a sensitivity and specificity of 83.3% and 98.8%, respectively. CONCLUSIONS: The 50-50 and bilirubin > 7-mg/dL rules were not accurate in predicting 90-day mortality. Rather, a composite integer-based risk score based on postoperative day 3 international normalized ratio, bilirubin, creatinine, and complication grade more accurately predicted 90-day mortality after hepatectomy. (J Am Coll Surg 2013; 216: 1049-1056. (C) 2013 by the American College of Surgeons)
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- 2013
18. Surgical management of patients with synchronous colorectal liver metastasis: a multicenter international analysis
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Skye C. Mayo, Timothy M. Pawlik, Michael A. Choti, Gilles Mentha, Hugo Marques, Luca Aldrighetti, Christopher L. Wolfgang, Jorge Lamelas, Eduardo Barrosso, Carlo Pulitano, Isabelle Gindrat, Wassila De Saussure, Mayo, Sc, Pulitano, C, Marques, H, Lamelas, J, Wolfgang, Cl, de Saussure, W, Choti, Ma, Gindrat, I, Aldrighetti, L, Barrosso, E, Mentha, G, and Pawlik, Tm
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Male ,medicine.medical_specialty ,Colorectal cancer ,Bilateral Disease ,International Cooperation ,Simultaneous resection ,Article ,Metastasis ,Liver Neoplasms/secondary/surgery ,medicine ,Humans ,Colorectal Neoplasms/pathology/surgery ,ddc:617 ,business.industry ,Hazard ratio ,Liver Neoplasms ,Middle Aged ,medicine.disease ,digestive system diseases ,Surgery ,Multicenter study ,Postoperative mortality ,Liver operation ,Female ,business ,Colorectal Neoplasms - Abstract
BACKGROUND: The goal of this study was to investigate the surgical management and outcomes of patients with primary colorectal cancer (CRC) and synchronous liver metastasis (sCRLM). STUDY DESIGN: Using a multi-institutional database, we identified 1,004 patients treated for sCRLM between 1982 and 2011. Clinicopathologic and outcomes data were evaluated with uni- and multivariable analyses. RESULTS: A simultaneous CRC and liver operation was performed in 329 (33%) patients; 675 (67%) underwent a staged approach ("classic" staged approach, n = 647; liver-first strategy, n = 28). Patients managed with the liver-first approach had more hepatic lesions and were more likely to have bilateral disease than those in the other 2 groups (p < 0.05). The use of staged operative strategies increased over the time of the study from 58% to 75% (p < 0.001). Liver-directed therapy included hepatectomy (90%) or combined resection + ablation (10%). A major resection (>3 segments) was more common with a staged approach (39% vs 24%; p < 0.001). Overall, 509 patients (50%) received chemotherapy in either the preoperative (22%) or adjuvant (28%) settings, with 11% of patients having both. There were 197 patients (20%) who had a complication in the postoperative period, with no difference in morbidity between staged and simultaneous groups or major vs minor hepatectomies (p > 0.05). Ninety-day postoperative mortality was 3.0%, with no difference between simultaneous and staged approaches (p = 0.94). The overall median and 5-year survivals were 50.9 months and 44%, respectively; long-term survival was the same regardless of the operative approach (p > 0.05). CONCLUSIONS: Simultaneous and staged resections for sCRLM can be performed with comparable morbidity, mortality, and long-term oncologic outcomes. (J Am Coll Surg 2013; 216: 707-718. (C) 2013 by the American College of Surgeons)
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- 2013
19. The Significance of Circulating Tumor Cells in Pancreatic Cancer.
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Habib JR, Javed AA, and Wolfgang CL
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- Humans, Prognosis, Neoplastic Cells, Circulating pathology, Pancreatic Neoplasms pathology, Pancreatic Neoplasms blood, Pancreatic Neoplasms therapy, Pancreatic Neoplasms mortality, Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal blood, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal therapy, Carcinoma, Pancreatic Ductal surgery
- Abstract
The notion that technically resectable pancreatic ductal adenocarcinoma presents as localized disease is now known to be inaccurate. Evidence supports that most patients have subclinical systemic dissemination at the time of diagnosis. It is now widely accepted that both a local and systemic component of disease coexist, each requiring treatment of improved survival and potential cure. The advent of multiagent chemotherapy regimens has resulted in a modest improvement in survival. Consequently, this article will emphasize the expanding potential and significance of circulating tumor cells in the prognostication and management of patients with pancreatic cancer., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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20. Corrigendum to "The 2016 update of the International Study Group (ISGPF) definition and grading of postoperative pancreatic fistula: eleven years after." Surgery 2017. Mar; 161 (3):584-591. Epub Dec 28, 2016.
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Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, Allen P, Andersson R, Asbun HJ, Besselink MG, Conlon K, Del Chiaro M, Falconi M, Fernandez-Cruz L, Fernandez-Del Castillo C, Fingerhut A, Friess H, Gouma DJ, Hackert T, Izbicki J, Lillemoe KD, Neoptolemos JP, Olah A, Schulick R, Shrikhande SV, Takada T, Takaori K, Traverso W, Vollmer CR, Wolfgang CL, Yeo CJ, Salvia R, and Buchler M
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- 2024
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21. ASO Visual Abstract: Predictors for Long-Term Survival After Resection of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.
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Javed AA, Mahmud O, Fatimi AS, Habib A, Grewal M, He J, Wolfgang CL, and Besselink MG
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- Humans, Survival Rate, Prognosis, Pancreatectomy mortality, Pancreatectomy methods, Carcinoma, Pancreatic Ductal surgery, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal pathology, Pancreatic Neoplasms surgery, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology
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- 2024
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22. ASO Author Reflections: The Role of Established Prognostic Factors in Long-Term Survival After Resection of Pancreatic Ductal Adenocarcinoma.
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Mahmud O, Javed AA, Fatimi AS, Habib A, Grewal M, He J, Wolfgang CL, and Besselink MG
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- Humans, Prognosis, Survival Rate, Pancreatectomy mortality, Pancreatectomy methods, Carcinoma, Pancreatic Ductal surgery, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal pathology, Pancreatic Neoplasms surgery, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology
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- 2024
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23. Surgical Outcome After Distal Pancreatectomy With and Without Portomesenteric Venous Resection in Patients with Pancreatic Adenocarcinoma: A Transatlantic Evaluation of Patients in North America, Germany, Sweden, and The Netherlands (GAPASURG).
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Stoop TF, Augustinus S, Björnsson B, Tingstedt B, Andersson B, Wolfgang CL, Werner J, Johansen K, Stommel MWJ, Katz MHG, Ghadimi M, House MG, Ghorbani P, Molenaar IQ, de Wilde RF, Mieog JSD, Keck T, Wellner UF, Uhl W, Besselink MG, Pitt HA, and Del Chiaro M
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Background: Pancreatic adenocarcinoma located in the pancreatic body might require a portomesenteric venous resection (PVR), but data regarding surgical risks after distal pancreatectomy (DP) with PVR are sparse. Insight into additional surgical risks of DP-PVR could support preoperative counseling and intraoperative decision making. This study aimed to provide insight into the surgical outcome of DP-PVR, including its potential risk elevation over standard DP., Methods: We conducted a retrospective, multicenter study including all patients with pancreatic adenocarcinoma who underwent DP ± PVR (2018-2020), registered in four audits for pancreatic surgery from North America, Germany, Sweden, and The Netherlands. Patients who underwent concomitant arterial and/or multivisceral resection(s) were excluded. Predictors for in-hospital/30-day major morbidity and mortality were investigated by logistic regression, correcting for each audit., Results: Overall, 2924 patients after DP were included, of whom 241 patients (8.2%) underwent DP-PVR. Rates of major morbidity (24% vs. 18%; p = 0.024) and post-pancreatectomy hemorrhage grade B/C (10% vs. 3%; p = 0.041) were higher after DP-PVR compared with standard DP. Mortality after DP-PVR and standard DP did not differ significantly (2% vs. 1%; p = 0.542). Predictors for major morbidity were PVR (odds ratio [OR] 1.500, 95% confidence interval [CI] 1.086-2.071) and conversion from minimally invasive to open surgery (OR 1.420, 95% CI 1.032-1.970). Predictors for mortality were higher age (OR 1.087, 95% CI 1.045-1.132), chronic obstructive pulmonary disease (OR 4.167, 95% CI 1.852-9.374), and conversion from minimally invasive to open surgery (OR 2.919, 95% CI 1.197-7.118), whereas concomitant PVR was not associated with mortality., Conclusions: PVR during DP for pancreatic adenocarcinoma in the pancreatic body is associated with increased morbidity, but can be performed safely in terms of mortality., (© 2024. The Author(s).)
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- 2024
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24. Progression of Site-specific Recurrence of Pancreatic Cancer and Implications for Treatment.
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Rompen IF, Levine J, Habib JR, Sereni E, Mughal N, Hewitt DB, Sacks GD, Welling TH, Simeone DM, Kaplan B, Berman RS, Cohen SM, Wolfgang CL, and Javed AA
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- Humans, Male, Female, Retrospective Studies, Aged, Middle Aged, Pancreatectomy, Survival Rate, Prognosis, Pancreatic Neoplasms surgery, Pancreatic Neoplasms pathology, Pancreatic Neoplasms mortality, Pancreatic Neoplasms therapy, Neoplasm Recurrence, Local, Carcinoma, Pancreatic Ductal surgery, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal therapy, Disease Progression
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Objective: To analyze postrecurrence progression in the context of recurrence sites and assess implications for postrecurrence treatment., Background: Most patients with resected pancreatic ductal adenocarcinoma (PDAC) recur within 2 years. Different survival outcomes for location-specific patterns of recurrence are reported, highlighting their prognostic value. However, a lack of understanding of postrecurrence progression and survival remains., Methods: This retrospective analysis included surgically treated patients with PDAC at NYU Langone Health (2010-2021). Sites of recurrence were identified at the time of diagnosis and further follow-up. Kaplan-Meier curves, log-rank test, and Cox regression analyses were applied to assess survival outcomes., Results: Recurrence occurred in 57.3% (196/342) patients with a median time to recurrence of 11.3 months (95% CI: 12.6-16.5). The first site of recurrence was local in 43.9% of patients, liver in 23.5%, peritoneal in 8.7%, lung in 3.6%, whereas 20.4% had multiple sites of recurrence. Progression to secondary sites was observed in 11.7%. Only lung involvement was associated with significantly longer survival after recurrence compared with other sites (16.9 vs 8.49 months, P = 0.003). In local recurrence, 21 (33.3%) patients were alive after 1 year without progression to secondary sites. This was associated with a CA19-9 of <100 U/mL at the time of primary diagnosis ( P = 0.039), nodal negative disease ( P = 0.023), and well-moderate differentiation ( P = 0.042) compared with patients with progression., Conclusion: Except for lung recurrence, postrecurrence survival after PDAC resection is associated with poor survival. A subset of patients with local-only recurrence do not quickly succumb to systemic spread. This is associated with markers for favorable tumor biology, making them candidates for potential curative re-resections when feasible., Competing Interests: I.F.R. is supported by the Swiss National Science Foundation (SNSF). The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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25. Outcomes in intraductal papillary mucinous neoplasm-derived pancreatic cancer differ from PanIN-derived pancreatic cancer.
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Habib JR, Rompen IF, Javed AA, Grewal M, Kinny-Köster B, Andel PCM, Hewitt DB, Sacks GD, Besselink MG, van Santvoort HC, Daamen LA, Loos M, He J, Büchler MW, Wolfgang CL, and Molenaar IQ
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Background and Aim: Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) management is generally extrapolated from pancreatic intraepithelial neoplasia (PanIN)-derived PDAC guidelines. However, these are biologically divergent, and heterogeneity further exists between tubular and colloid subtypes., Methods: Consecutive upfront surgery patients with PanIN-derived and IPMN-derived PDAC were retrospectively identified from international centers (2000-2019). One-to-one propensity score matching for clinicopathologic factors generated three cohorts: IPMN-derived versus PanIN-derived PDAC, tubular IPMN-derived versus PanIN-derived PDAC, and tubular versus colloid IPMN-derived PDAC. Overall survival (OS) was compared using Kaplan-Meier and log-rank tests. Multivariable Cox regression determined corresponding hazard ratios (HR) and 95% confidence intervals (95% CI)., Results: The median OS (mOS) in 2350 PanIN-derived and 700 IPMN-derived PDAC patients was 23.0 and 43.1 months (P < 0.001), respectively. PanIN-derived PDAC had worse T-stage, CA19-9, grade, and nodal status. Tubular subtype had worse T-stage, CA19-9, grade, nodal status, and R1 margins, with a mOS of 33.7 versus 94.1 months (P < 0.001) in colloid. Matched (n = 495), PanIN-derived and IPMN-derived PDAC had mOSs of 30.6 and 42.8 months (P < 0.001), respectively. In matched (n = 341) PanIN-derived and tubular IPMN-derived PDAC, mOS remained poorer (27.7 vs 37.4, P < 0.001). Matched tubular and colloid cancers (n = 112) had similar OS (P = 0.55). On multivariable Cox regression, PanIN-derived PDAC was associated with worse OS than IPMN-derived (HR: 1.66, 95% CI: 1.44-1.90) and tubular IPMN-derived (HR: 1.53, 95% CI: 1.32-1.77) PDAC. Colloid and tubular subtype was not associated with OS (P = 0.16)., Conclusions: PanIN-derived PDAC has worse survival than IPMN-derived PDAC supporting distinct outcomes. Although more indolent, colloid IPMN-derived PDAC has similar survival to tubular after risk adjustment., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2024
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26. Complexity and Experience Grading to Guide Patient Selection for Minimally-invasive Pancreatoduodenectomy: An ISGPS Consensus.
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Barreto SG, Strobel O, Salvia R, Marchegiani G, Wolfgang CL, Werner J, Ferrone CR, Abu Hilal M, Boggi U, Butturini G, Falconi M, Fernandez-Del Castillo C, Friess H, Fusai GK, Halloran CM, Hogg M, Jang JY, Kleeff J, Lillemoe KD, Miao Y, Nagakawa Y, Nakamura M, Probst P, Satoi S, Siriwardena AK, Vollmer CM, Zureikat A, Zyromski NJ, Asbun HJ, Dervenis C, Neoptolemos JP, Büchler MW, Hackert T, Besselink MG, and Shrikhande SV
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Objective: The ISGPS aims to develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally-invasive pancreatoduodenectomy (MIPD)., Background: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis towards appropriate patient selection according to adequate surgeon and center experience., Methods: The ISGPS developed a complexity and experience grading system to guide patient selection for MIPD based on an evidence-based review and a series of discussions., Results: The ISGPS complexity and experience grading system for MIPD is subclassified into patient-related risk factors and provider experience-related variables. The patient-related risk factors include anatomical (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors, all incorporated in an A-B-C classification, graded as no, a single, and multiple risk factors. The surgeon and center experience-related variables include surgeon total MIPD experience (cut-offs 40 and 80) and center annual MIPD volume (cut-offs 10 and 30), all also incorporated in an A-B-C classification., Conclusion: This ISGPS complexity and experience grading system for robotic and laparoscopic MIPD may enable surgeons to optimally select patients after duly considering specific risk factors known to influence the complexity of the procedure. This grading system will likely allow for a thoughtful and stepwise implementation of MIPD and facilitate a fair comparison of outcome between centers and countries., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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27. What is the optimal surgical approach for ductal adenocarcinoma of the pancreatic neck? - a retrospective cohort study.
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Rompen IF, Habib JR, Sereni E, Stoop TF, Musa J, Cohen SM, Berman RS, Kaplan B, Hewitt DB, Sacks GD, Wolfgang CL, and Javed AA
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- Humans, Male, Female, Retrospective Studies, Aged, Middle Aged, Lymph Node Excision, Cohort Studies, Carcinoma, Pancreatic Ductal surgery, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal pathology, Pancreatic Neoplasms surgery, Pancreatic Neoplasms pathology, Pancreatic Neoplasms mortality, Pancreatectomy methods, Pancreaticoduodenectomy methods, Pancreaticoduodenectomy mortality
- Abstract
Background: The appropriate surgical approach for pancreatic ductal adenocarcinoma (PDAC) is determined by the tumor's relation to the porto-mesenteric axis. Although the extent and location of lymphadenectomy is dependent on the type of resection, a pancreatoduodenectomy (PD), distal pancreatectomy (DP), or total pancreatectomy (TP) are considered equivalent oncologic operations for pancreatic neck tumors. Therefore, we aimed to assess differences in histopathological and oncological outcomes for surgical approaches in the treatment of pancreatic neck tumors., Methods: Patients with resected PDAC located in the pancreatic neck were identified from the National Cancer Database (2004-2020). Patients with metastatic disease were excluded. Furthermore, patients with 90-day mortality and R2-resections were excluded from the multivariable Cox-regression analysis., Results: Among 846 patients, 58% underwent PD, 25% DP, and 17% TP with similar R0-resection rates (p = 0.722). Significant differences were observed in nodal positivity (PD:44%, DP:34%, TP:57%, p < 0.001) and mean-number of examined lymph nodes (PD:17.2 ± 10.4, DP:14.7 ± 10.5, TP:21.2 ± 11.0, p < 0.001). Furthermore, inadequate lymphadenectomy (< 12 nodes) was observed in 30%, 44%, and 19% of patients undergoing PD, DP, and TP, respectively (p < 0.001). Multivariable analysis yielded similar overall survival after DP (HR:0.83, 95%CI:0.63-1.11), while TP was associated with worse survival (HR:1.43, 95%CI:1.08-1.89) compared to PD., Conclusion: While R0-rates are similar amongst all approaches, DP is associated with inadequate lymphadenectomy which may result in understaging disease. However, this had no negative influence on survival. In the premise that an oncological resection of the pancreatic neck tumor is feasible with a partial pancreatectomy, no benefit is observed by performing a TP., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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28. An international Multi-Institutional validation of T1 Sub-staging of intraductal papillary mucinous neoplasm-derived pancreatic cancer.
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Habib JR, Rompen IF, Campbell BA, Andel PCM, Kinny-Köster B, Damaseviciute R, Brock Hewitt D, Sacks GD, Javed AA, Besselink MG, van Santvoort HC, Daamen LA, Loos M, He J, Quintus Molenaar I, Büchler MW, and Wolfgang CL
- Abstract
Background: Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared to its biologically distinct counterpart, pancreatic intraepithelial neoplasia (PanIN)-derived PDAC. Thus, experts proposed T1 sub-staging for IPMN-derived PDAC. However, this has never been validated., Methods: Consecutive upfront surgery patients with IPMN-derived PDAC from five international high-volume centers were classified by the proposed T1 sub-staging classification (T1a ≤ 0.5, T1b > 0.5 and ≤1.0, and T1c >1.0 and ≤2.0 cm) using the invasive component size. Kaplan-Meier and log-rank tests were utilized to compare overall survival (OS). A multivariable Cox-regression was used to determine hazard ratios (HR) with confidence intervals (95%CI)., Results: Among 747 patients, 69 (9.2%), 50 (6.7%), 99 (13.0%), and 531 patients (71.1%), comprised the T1a, T1b, T1c, and T2-4 subgroups, respectively. Increasing T-stage was associated with elevated CA19-9, poorer grade, nodal positivity, R1-margin, and tubular subtype. Median OS for T1a, T1b, T1c, and T2-4 were 159.0 (95%CI:126.0-NR), 128.8 (98.3-NR), 77.6 (48.3-108.2), and 31.4 (27.5-37.7) months, respectively (p < .001). OS decreased with increasing T-stage for all pairwise comparisons (all p < .05). After risk-adjustment, age > 65, elevated CA19-9, T1b [HR : 2.55 (1.22-5.32)], T1c [HR : 3.04 (1.60-5.76)], and T2-4 [HR : 3.41 (1.89-6.17)] compared to T1a, nodal positivity, R1-margin, and no adjuvant chemotherapy were associated with worse OS. Disease recurrence was more common in T2-4 tumors (56.4%) compared to T1a (18.2%), T1b (23.9%), and T1c (36.1%, p < .001)., Conclusion: T1 sub-staging of IPMN-derived PDAC is valid and has significant prognostic value. Advancing T1 sub-stage is associated with worse histopathology, survival, and recurrence. T1 sub-staging is recommended for future guidelines., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2024
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29. Predictors for Long-Term Survival After Resection of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.
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Javed AA, Mahmud O, Fatimi AS, Habib A, Grewal M, He J, Wolfgang CL, and Besselink MG
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- Humans, Survival Rate, Prognosis, Pancreatectomy mortality, Carcinoma, Pancreatic Ductal surgery, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal pathology, Pancreatic Neoplasms surgery, Pancreatic Neoplasms pathology, Pancreatic Neoplasms mortality
- Abstract
Background: Improved systemic therapy has made long term (≥ 5 years) overall survival (LTS) after resection of pancreatic ductal adenocarcinoma (PDAC) increasingly common. However, a systematic review on predictors of LTS following resection of PDAC is lacking., Methods: The PubMed, Embase, Scopus, and Cochrane CENTRAL databases were systematically searched from inception until March 2023. Studies reporting actual survival data (based on follow-up and not survival analysis estimates) on factors associated with LTS were included. Meta-analyses were conducted by using a random effects model, and study quality was gauged by using the Newcastle-Ottawa Scale (NOS)., Results: Twenty-five studies with 27,091 patients (LTS: 2,132, non-LTS: 24,959) who underwent surgical resection for PDAC were meta-analyzed. The median proportion of LTS patients was 18.32% (IQR 12.97-21.18%) based on 20 studies. Predictors for LTS included sex, body mass index (BMI), preoperative levels of CA19-9, CEA, and albumin, neutrophil-lymphocyte ratio, tumor grade, AJCC stage, lymphovascular and perineural invasion, pathologic T-stage, nodal disease, metastatic disease, margin status, adjuvant therapy, vascular resection, operative time, operative blood loss, and perioperative blood transfusion. Most articles received a "good" NOS assessment, indicating an acceptable risk of bias., Conclusions: Our meta-analysis pools all true follow up data in the literature to quantify associations between prognostic factors and LTS after resection of PDAC. While there appears to be evidence of a complex interplay between risk, tumor biology, patient characteristics, and management related factors, no single parameter can predict LTS after the resection of PDAC., (© 2024. The Author(s).)
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- 2024
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30. REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.
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Boggi U, Kauffmann E, Napoli N, Barreto SG, Besselink MG, Fusai GK, Hackert T, Abu Hilal M, Marchegiani G, Salvia R, Shrikhande SV, Truty M, Werner J, Wolfgang CL, Bannone E, Capretti G, Cattelani A, Coppola A, Cucchetti A, De Sio D, Di Dato A, Di Meo G, Fiorillo C, Gianfaldoni C, Ginesini M, Hidalgo Salinas C, Lai Q, Miccoli M, Montorsi R, Pagnanelli M, Poli A, Ricci C, Sucameli F, Tamburrino D, Viti V, Addeo PF, Alfieri S, Bachellier P, Baiocchi GL, Balzano G, Barbarello L, Brolese A, Busquets J, Butturini G, Caniglia F, Caputo D, Casadei R, Chunhua X, Colangelo E, Coratti A, Costa F, Crafa F, Dalla Valle R, De Carlis L, de Wilde RF, Del Chiaro M, Di Benedetto F, Di Sebastiano P, Dokmak S, Hogg M, Egorov VI, Ercolani G, Ettorre GM, Falconi M, Ferrari G, Ferrero A, Filauro M, Giardino A, Grazi GL, Gruttadauria S, Izbicki JR, Jovine E, Katz M, Keck T, Khatkov I, Kiguchi G, Kooby D, Lang H, Lombardo C, Malleo G, Massani M, Mazzaferro V, Memeo R, Miao Y, Mishima K, Molino C, Nagakawa Y, Nakamura M, Nardo B, Panaro F, Pasquali C, Perrone V, Rangelova E, Liu R, Romagnoli R, Romito R, Rosso E, Schulick R, Siriwardena A, Spampinato MG, Strobel O, Testini M, Troisi RI, Uzunoglo FG, Valente R, Veneroni L, Zerbi A, Vicente E, Vistoli F, Vivarelli M, Wakabayashi G, Zanus G, Zureikat A, Zyromski NJ, Coppola R, D'Andrea V, Davide J, Dervenis C, Frigerio I, Konlon KC, Michelassi F, Montorsi M, Nealon W, Portolani N, Sousa Silva D, Bozzi G, Ferrari V, Trivella MG, Cameron J, Clavien PA, and Asbun HJ
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- Humans, Delphi Technique, Practice Guidelines as Topic, Neoplasm Staging, Patient Selection, Pancreatic Neoplasms surgery, Pancreatic Neoplasms pathology, Perioperative Care standards, Pancreatectomy, Carcinoma, Pancreatic Ductal surgery, Carcinoma, Pancreatic Ductal pathology
- Abstract
Objective: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)., Background: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking., Methods: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines., Results: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ )., Conclusions: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population., Competing Interests: S.G.B.: support from Flinders Foundation grant: 49358025, NHMRC Ideas Grant: 2021009, Pankind 21.R7.INV.CB.UOSA.6.2. F.M.: Tsumura, Inc., Scientific Advisory Board. M.D.C. is a co-PI of a Boston Scientific–sponsored study and he has been awarded an industry grant by Haemonetics, Inc. M.H.: Intuitive Surgical—teaches courses and proctors. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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31. Factors associated with radiological misstaging of pancreatic ductal adenocarcinoma: A retrospective observational study.
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Yasrab M, Thakker S, Wright MJ, Ahmed T, He J, Wolfgang CL, Chu LC, Weiss MJ, Kawamoto S, Johnson PT, Fishman EK, and Javed AA
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- Humans, Retrospective Studies, Female, Male, Aged, Middle Aged, Diagnostic Errors, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms pathology, Carcinoma, Pancreatic Ductal diagnostic imaging, Carcinoma, Pancreatic Ductal pathology, Neoplasm Staging, Tomography, X-Ray Computed methods
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Purpose: Accurate staging of disease is vital in determining appropriate care for patients with pancreatic ductal adenocarcinoma (PDAC). It has been shown that the quality of scans and the experience of a radiologist can impact computed tomography (CT) based assessment of disease. The aim of the current study was to evaluate the impact of the rereading of outside hospital (OH) CT by an expert radiologist and a repeat pancreatic protocol CT (PPCT) on staging of disease., Methods: Patients evaluated at the our institute's pancreatic multidisciplinary clinic (2006 to 2014) with OH scan and repeat PPCT performed within 30 days were included. In-house radiologists staged disease using OH scans and repeat PPCT, and factors associated with misstaging were determined., Results: The study included 100 patients, with a median time between OH scan and PPCT of 19 days (IQR: 13-23 days.) Stage migration was mostly accounted for by upstaging of disease (58.8 % to 83.3 %) in all comparison groups. When OH scans were rereviewed, 21.5 % of the misstaging was due to missed metastases, however, when rereads were compared to the PPCT, occult metastases accounted for the majority of misstaged patients (62.5 %). Potential factors associated with misstaging were primarily related to imaging technique., Conclusion: A repeat PPCT results in increased detection of metastatic disease that rereviews of OH scans may otherwise miss. Accessible insurance coverage for repeat PPCT imaging even within 30 days of an OH scan could help optimize delivery of care and alleviate burdens associated with misstaging., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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32. The impact of metastatic sites on survival Rates and predictors of extended survival in patients with metastatic pancreatic cancer.
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Levine JM, Rompen IF, Franco JC, Swett B, Kryschi MC, Habib JR, Diskin B, Hewitt DB, Sacks GD, Kaplan B, Berman RS, Cohen SM, Wolfgang CL, and Javed AA
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Background Objectives: The aim of this study was to determine the role of site-specific metastatic patterns over time and assess factors associated with extended survival in metastatic PDAC. Half of all patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. The site of metastasis plays a crucial role in clinical decision making due to its prognostic value., Methods: We examined 56,757 stage-IV PDAC patients from the National Cancer Database (2016-2019), categorizing them by metastatic site: multiple, liver, lung, brain, bone, carcinomatosis, or other. The site-specific prognostic value was assessed using log-rank tests while time-varying effects were assessed by Aalen's linear hazards model. Factors associated with extended survival (>3years) were assessed with logistic regression., Results: Median overall survival (mOS) in patients with distant lymph node-only metastases (9.0 months) and lung-only metastases (8.1 months) was significantly longer than in patients with liver-only metastases (4.6 months, p < 0.001). However, after six months, the metastatic site lost prognostic value. Logistic regression identified extended survivors (3.6 %) as more likely to be younger, Hispanic, privately insured, Charlson-index <2, having received chemotherapy, or having undergone primary or distant site surgery (all p < 0.001)., Conclusion: While synchronous liver metastases are associated with worse outcomes than lung-only and lymph node-only metastases, this predictive value is diminished after six months. Therefore, treatment decisions beyond this time should not primarily depend on the metastatic site. Extended survival is possible in a small subset of patients with favorable tumor biology and good conditional status, who are more likely to undergo aggressive therapies., Competing Interests: Declaration of competing interest There are no conflicts of interest for any of the authors., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)
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- 2024
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33. ASO Visual Abstract: The Value of Textbook Outcome in Benchmarking Pancreatoduodenectomy for Nonfunctioning Pancreatic Neuroendocrine Tumors.
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Partelli S, Fermi F, Fusai GK, Tamburrino D, Lykoudis P, Beghdadi N, Dokmak S, Wiese D, Landoni L, Reich F, Busch ORC, Napoli N, Jang JY, Kwon W, Armstrong T, Allen PJ, He J, Javed A, Sauvanet A, Bartsch DK, Salvia R, van Dijkum EJMN, Besselink MG, Boggi U, Kim SW, Wolfgang CL, and Falconi M
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- Humans, Survival Rate, Prognosis, Pancreaticoduodenectomy methods, Pancreatic Neoplasms surgery, Pancreatic Neoplasms pathology, Benchmarking, Neuroendocrine Tumors surgery, Neuroendocrine Tumors pathology
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- 2024
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34. The Value of Textbook Outcome in Benchmarking Pancreatoduodenectomy for Nonfunctioning Pancreatic Neuroendocrine Tumors.
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Partelli S, Fermi F, Fusai GK, Tamburrino D, Lykoudis P, Beghdadi N, Dokmak S, Wiese D, Landoni L, Reich F, Busch ORC, Napoli N, Jang JY, Kwon W, Armstrong T, Allen PJ, He J, Javed A, Sauvanet A, Bartsch DK, Salvia R, van Dijkum EJMN, Besselink MG, Boggi U, Kim SW, Wolfgang CL, and Falconi M
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- Humans, Male, Female, Retrospective Studies, Middle Aged, Survival Rate, Follow-Up Studies, Aged, Neuroendocrine Tumors surgery, Neuroendocrine Tumors pathology, Prognosis, Length of Stay statistics & numerical data, Adult, Pancreaticoduodenectomy, Pancreatic Neoplasms surgery, Pancreatic Neoplasms pathology, Pancreatic Neoplasms mortality, Benchmarking, Postoperative Complications
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Background: Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs)., Patients and Methods: All patients who underwent PD for NF-PanNETs (2007-2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested., Results: Overall, 477 patients were included. The TO rate was 32%. Tumor size [odds ratio (OR) 1.696; p = 0.013], a minimally invasive approach (OR 12.896; p = 0.001), and surgical volume (OR 2.062; p = 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free (p = 0.487) and overall survival (p = 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2 cm was 35% versus 27% in patients with NF-PanNET ≤ 2 cm (p = 0.044). Considering only NF-PanNETs > 2 cm, patients with TO and those without TO had comparable 5-year overall survival rates (p = 0.766) CONCLUSIONS: TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival., (© 2024. Society of Surgical Oncology.)
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- 2024
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35. Caregiver-reported quality of communication in pancreatic and periampullary cancer.
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Fong ZV, Teinor J, Engineer L, Yeo TP, Rinaldi D, Greer JB, Lavu H, Qadan M, Johnston FM, Ferrone CR, Chang DC, Yeo CJ, Wolfgang CL, Warshaw AL, Lillemoe KD, Castillo CF, Weiss MJ, Wu AW, and Wolff JL
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- Humans, Male, Female, Middle Aged, Aged, Adult, Ampulla of Vater, Surveys and Questionnaires, Patient Readmission statistics & numerical data, Common Bile Duct Neoplasms surgery, Pancreatic Neoplasms surgery, Caregivers psychology, Communication, Pancreatectomy
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Background: Communication between caregivers and clinical team members is critical for transitional care, but its quality and potential impact on outcomes are not well understood. This study reports on caregiver-reported quality of communication with clinical team members in the postpancreatectomy period and examines associations of these reports with patient and caregiver outcomes., Methods: Caregivers of patients with pancreatic and periampullary malignancies who had undergone pancreatectomy were surveyed. Instrument measures assessed care experiences using the Caregiver Perceptions About Communication with Clinical Team Members (CAPACITY) instrument. The instrument has two main subscales: communication, assessing the extent to which providers helped caregivers comprehend details of clinical visits, and capacity, defined as the extent to which providers assessed whether caregivers were able to care for patients., Results: Of 265 caregivers who were approached, 240 (90.6%) enrolled in the study. The mean communication and capacity subscale scores were 2.7 ± 0.6 and 1.5 ± 0.6, respectively (range, 0-4 [higher = better]). Communication subscale scores were lower among caregivers of patients who experienced (vs. those who did not experience) a 30-day readmission (2.6 ± 0.5 vs. 2.8 ± 0.6, respectively; p = .047). Capacity subscale scores were inversely associated with restriction in patient daily activities (a 0.04 decrement in the capacity score for every 1 point in daily activity restriction; p = .008)., Conclusions: After pancreatectomy, patients with pancreatic and periampullary cancer whose caregivers reported worse communication with care providers were more likely to experience readmission. Caregivers of patients with greater daily activity restrictions were less likely to report being asked about the caregiver's skill and capacity by clinicians., Plain Language Summary: This prospective study used a validated survey instrument and reports on the quality of communication between health care providers and caregivers as reported by caregivers of patients with pancreatic and periampullary cancer after pancreatectomy. In an analysis of 240 caregivers enrolled in the study, lower communication scores (the extent to which providers helped caregivers understand clinical details) were associated with higher odds of 30-day patient readmission to the hospital. In addition, lower capacity scores (the extent to which providers assessed caregivers' ability to care for patients) were associated with greater impairment in caregivers. The strikingly low communication quality and capacity assessment scores suggest substantial room for improvement, with the potential to improve both caregiver and patient outcomes., (© 2023 American Cancer Society.)
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- 2024
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36. Quantifying Patient Risk Threshold in Managing Pancreatic Intraductal Papillary Mucinous Neoplasms.
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Kaslow SR, Sharma AR, Hewitt DB, Bridges JFP, Javed AA, Wolfgang CL, Braithwaite S, and Sacks GD
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Objective: We aimed to better understand patients' treatment preferences and quantify the level of cancer risk at which treatment preferences change (risk threshold) to inform better counseling of patients with intraductal papillary mucinous neoplasms (IPMNs)., Summary Background Data: The complexity of IPMN management provides an opportunity to align treatment with individual preference., Methods: We surveyed a sample of healthy volunteers simulating a common scenario: undergoing an imaging study that incidentally identifies an IPMN. In the scenario, the estimated risk of cancer in the IPMN was 5%. Patients were asked their treatment preference (surgery or surveillance), to quantify the level of cancer risk in the IPMN at which their treatment preference would change (i.e. risk threshold), and their level of cancer anxiety as measured on a 5-point Likert scale. We examined associations between participant characteristics, treatment preferences, and risk threshold using multivariable linear regression., Results: The median risk threshold among the 520 participants was 25% (IQR 2.3-50%). The risk threshold had a bimodal distribution: 40% of participants had a risk threshold between 0-10% and 47% had a risk threshold above 30%. When informed that the risk of cancer was 5%, 62% of participants (n=323) preferred surveillance, and the remaining 38% (n=197) preferred surgery. After adjusting for potential confounders, participants who expressed "worry" or "extreme worry" about the malignancy risk of IPMN had significantly lower risk thresholds than participants who were "not at all worried" (Coefficient -12, 95%CI -21 to -2, P=0.015 and Coefficient -18, 95%CI -29 to -8, P<0.001, respectively)., Conclusions: Participants varied in treatment preference and risk threshold of incidentally identified IPMNs. Given the uncertainty in estimating the true malignant potential of IPMNs, a better understanding of a patient's risk threshold, as influenced by patient concern about malignancy, will help inform the shared decision-making process., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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37. Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma.
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Guinn S, Kinny-Köster B, Tandurella JA, Mitchell JT, Sidiropoulos DN, Loth M, Lyman MR, Pucsek AB, Zabransky DJ, Lee JW, Kartalia E, Ramani M, Seppälä TT, Cherry C, Suri R, Zlomke H, Patel J, He J, Wolfgang CL, Yu J, Zheng L, Ryan DP, Ting DT, Kimmelman A, Gupta A, Danilova L, Elisseeff JH, Wood LD, Stein-O'Brien G, Kagohara LT, Jaffee EM, Burkhart RA, Fertig EJ, and Zimmerman JW
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- Humans, Organoids pathology, Organoids metabolism, Vascular Endothelial Growth Factor A metabolism, Vascular Endothelial Growth Factor A genetics, Neuropilin-1 metabolism, Neuropilin-1 genetics, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Cell Communication, Epithelial-Mesenchymal Transition, Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal metabolism, Carcinoma, Pancreatic Ductal genetics, Cancer-Associated Fibroblasts metabolism, Cancer-Associated Fibroblasts pathology, Pancreatic Neoplasms pathology, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms genetics, Inflammation pathology, Inflammation metabolism, Tumor Microenvironment, Integrin beta1 metabolism, Integrin beta1 genetics, Coculture Techniques, Single-Cell Analysis
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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells. Transfer learning using transcriptional data from patient-derived organoid and CAF cocultures provided in silico validation of CAF induction of inflammatory and EMT epithelial cell states. Further experimental validation in cocultures demonstrated integrin beta 1 (ITGB1) and vascular endothelial factor A (VEGFA) interactions with neuropilin-1 mediating CAF-epithelial cell cross-talk. Together, this study introduces transfer learning from human single-cell data to organoid coculture analyses for experimental validation of discoveries of cell-cell cross-talk and identifies fibroblast-mediated regulation of EMT and inflammation., Significance: Adaptation of transfer learning to relate human single-cell RNA sequencing data to organoid-CAF cocultures facilitates discovery of human pancreatic cancer intercellular interactions and uncovers cross-talk between CAFs and tumor cells through VEGFA and ITGB1., (©2024 American Association for Cancer Research.)
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- 2024
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38. Defining the Minimal and Optimal Thresholds for Lymph Node Resection and Examination for Intraductal Papillary Mucinous Neoplasm Derived Pancreatic Cancer: A Multicenter Retrospective Analysis.
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Habib JR, Rompen IF, Kaslow SR, Grewal M, Andel PCM, Zhang S, Hewitt DB, Cohen SM, van Santvoort HC, Besselink MG, Molenaar IQ, He J, Wolfgang CL, Javed AA, and Daamen LA
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Objective: To establish minimal and optimal lymphadenectomy thresholds for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and evaluate their prognostic value., Background: Current guidelines recommend a minimum of 12-15 lymph nodes (LNs) in PDAC. This is largely based on pancreatic intraepithelial neoplasia (PanIN)-derived PDAC, a biologically distinct entity from IPMN-derived PDAC., Methods: Multicenter retrospective study including consecutive patients undergoing upfront surgery for IPMN-derived PDAC was conducted. The minimum cut-off for lymphadenectomy was defined as the maximum number of LNs where a significant node positivity difference was observed. Maximally selected log-rank statistic was used to derive the optimal lymphadenectomy cut-off (maximize survival). Kaplan-Meier curves and log-rank tests were used to analyze overall survival (OS) and recurrence-free survival (RFS). Multivariable Cox-regression was used to determine hazard ratios (HR) with 95% confidence intervals (95%CI)., Results: In 341 patients with resected IPMN-derived PDAC, the minimum number of LNs needed to ensure accurate nodal staging was 10 (P=0.040), whereas ≥20 LNs was the optimal number associated with improved OS (80.3 vs. 37.2 mo, P<0.001). Optimal lymphadenectomy was associated with improved OS [HR:0.57 (95%CI 0.39-0.83)] and RFS [HR:0.70 (95%CI 0.51-0.97)] on multivariable Cox-regression. On sub-analysis the optimal lymphadenectomy cut-offs for pancreatoduodenectomy, distal pancreatectomy, and total pancreatectomy were 20 (P<0.001), 23 (P=0.160), and 25 (P=0.008)., Conclusion: In IPMN-derived PDAC, lymphadenectomy with at least 10 lymph nodes mitigates under-staging, and at least 20 lymph nodes is associated with the improved survival. Specifically, for pancreatoduodenectomy and total pancreatectomy, 20 and 25 lymph nodes were the optimal cut-offs., Competing Interests: Disclosures: There are no conflicts of interest for any of the authors. The corresponding authors had full access to all data and take full responsibility for the veracity of the data and statistical analysis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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39. The Role of Intraoperative Pancreatoscopy in the Surgical Management of Intraductal Papillary Mucinous Neoplasms: A Scoping Review.
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Grewal M, Habib JR, Paluszek O, Cohen SM, Wolfgang CL, and Javed AA
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- Humans, Retrospective Studies, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms surgery, Neoplasms, Cystic, Mucinous, and Serous diagnostic imaging, Neoplasms, Cystic, Mucinous, and Serous surgery, Carcinoma, Pancreatic Ductal diagnostic imaging, Carcinoma, Pancreatic Ductal surgery, Carcinoma, Pancreatic Ductal pathology
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Objectives: Most patients with intraductal papillary mucinous neoplasms (IPMNs) are diagnosed with a solitary lesion; however, the presence of skip lesions, not appreciable on imaging, has been described. Postoperatively, these missed lesions can continue to grow and potentially become cancerous. Intraoperative pancreatoscopy (IOP) may facilitate detection of such skip lesions in the remnant gland. The aim of this scoping review was to appraise the evidence on the role of IOP in the surgical management of IPMNs., Materials and Methods: Studies reporting on the use of IOP during IPMN surgery were identified through searches of the PubMed, Embase, and Scopus databases. Data extracted included IOP findings, surgical plan modifications, and patient outcomes. The primary outcome of interest was the utility of IOP in surgical decision making., Results: Ten studies reporting on the use of IOP for IPMNs were identified, representing 147 patients. A total of 46 skip lesions were identified by IOP. Overall, surgical plans were altered in 37% of patients who underwent IOP. No IOP-related complications were reported., Conclusions: The current literature suggests a potential role of integration of IOP into the management of patients with IPMNs. This tool is safe and feasible and can result in changes in surgical decision making., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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40. Dynamics of Serum CA19-9 in Patients Undergoing Pancreatic Cancer Resection.
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van Oosten AF, Groot VP, Dorland G, Burkhart RA, Wolfgang CL, van Santvoort HC, He J, Molenaar IQ, and Daamen LA
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- Humans, CA-19-9 Antigen, Prognosis, Retrospective Studies, Biomarkers, Tumor, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local pathology, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms surgery, Pancreatic Neoplasms pathology, Carcinoma, Pancreatic Ductal diagnosis, Carcinoma, Pancreatic Ductal surgery, Carcinoma, Pancreatic Ductal pathology
- Abstract
Background: Carbohydrate antigen (CA) 19-9 is an established perioperative prognostic biomarker for pancreatic ductal adenocarcinoma (PDAC). However, it is unclear how CA19-9 monitoring should be used during postoperative surveillance to detect recurrence and to guide the initiation of recurrence-focused therapy., Objective: This study aimed to elucidate the value of CA19-9 as a diagnostic biomarker for disease recurrence in patients who underwent PDAC resection., Methods: Serum CA19-9 levels at diagnosis, after surgery, and during postoperative follow-up were analyzed in patients who underwent PDAC resection. All patients with at least two postoperative follow-up CA19-9 measurements before recurrence were included. Patients deemed to be nonsecretors of CA19-9 were excluded. The relative increase in postoperative CA19-9 was calculated for each patient by dividing the maximum postoperative CA19-9 value by the first postoperative value. Receiver operating characteristic analysis was performed to identify the optimal threshold for the relative increase in CA19-9 levels to identify recurrence in the training set using Youden's index. The performance of this cutoff was validated in a test set by calculating the area under the curve (AUC) and was compared to the performance of the optimal cutoff for postoperative CA19-9 measurements as a continuous value. In addition, sensitivity, specificity, and predictive values were assessed., Results: In total, 271 patients were included, of whom 208 (77%) developed recurrence. Receiver operating characteristic analysis demonstrated that a relative increase in postoperative serum CA19-9 of 2.6× was predictive of recurrence, with 58% sensitivity, 83% specificity, 95% positive predictive value, and 28% negative predictive value. The AUC for a 2.6× relative increase in the CA19-9 level was 0.719 in the training set and 0.663 in the test set. The AUC of postoperative CA19-9 as a continuous value (optimal threshold, 52) was 0.671 in the training set. In the training set, the detection of a 2.6-fold increase in CA19-9 preceded the detection of recurrence by a mean difference of 7 months ( P <0.001) and in the test set by 10 months ( P <0.001)., Conclusions: A relative increase in the postoperative serum CA19-9 level of 2.6-fold is a stronger predictive marker for recurrence than a continuous CA19-9 cutoff. A relative CA19-9 increase can precede the detection of recurrence on imaging for up to 7 to 10 months. Therefore, CA19-9 dynamics can be used as a biomarker to guide the initiation of recurrence-focused treatment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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41. International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas.
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Ohtsuka T, Fernandez-Del Castillo C, Furukawa T, Hijioka S, Jang JY, Lennon AM, Miyasaka Y, Ohno E, Salvia R, Wolfgang CL, and Wood LD
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- Humans, Pancreas, Endosonography, Pancreatic Intraductal Neoplasms diagnosis, Pancreatic Intraductal Neoplasms surgery, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms surgery, Carcinoma, Pancreatic Ductal diagnostic imaging, Carcinoma, Pancreatic Ductal surgery
- Abstract
This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and mainly focused on five topics; the revision of high-risk stigmata (HRS) and worrisome features (WF), surveillance of non-resected IPMN, surveillance after resection of IPMN, revision of pathological aspects, and investigation of molecular markers in cyst fluid. A new development from the prior guidelines is that systematic reviews were performed for each one of these topics, and published separately to provide evidence-based recommendations. One of the highlights of these new "evidence-based guidelines" is to propose a new management algorithm, and one major revision is to include into the assessment of HRS and WF the imaging findings from endoscopic ultrasound (EUS) and the results of cytological analysis from EUS-guided fine needle aspiration technique, when this is performed. Another key element of the current guidelines is to clarify whether lifetime surveillance for small IPMNs is required, and recommends two options, "stop surveillance" or "continue surveillance for possible development of concomitant pancreatic ductal adenocarcinoma", for small unchanged BD-IPMN after 5 years surveillance. Several other points are also discussed, including identifying high-risk features for recurrence in patients who underwent resection of non-invasive IPMN with negative surgical margin, summaries of the recent observations in the pathology of IPMN. In addition, the emerging role of cyst fluid markers that can aid in distinguishing IPMN from other pancreatic cysts and identify those IPMNs that harbor high-grade dysplasia or invasive carcinoma is discussed., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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42. Deep neural network-based segmentation of normal and abnormal pancreas on abdominal CT: evaluation of global and local accuracies.
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Kawamoto S, Zhu Z, Chu LC, Javed AA, Kinny-Köster B, Wolfgang CL, Hruban RH, Kinzler KW, Fouladi DF, Blanco A, Shayesteh S, and Fishman EK
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- Humans, Artificial Intelligence, Image Processing, Computer-Assisted methods, Tomography, X-Ray Computed methods, Neural Networks, Computer, Pancreas diagnostic imaging, Pancreatic Neoplasms diagnostic imaging, Carcinoma, Pancreatic Ductal
- Abstract
Purpose: Delay in diagnosis can contribute to poor outcomes in pancreatic ductal adenocarcinoma (PDAC), and new tools for early detection are required. Recent application of artificial intelligence to cancer imaging has demonstrated great potential in detecting subtle early lesions. The aim of the study was to evaluate global and local accuracies of deep neural network (DNN) segmentation of normal and abnormal pancreas with pancreatic mass., Methods: Our previously developed and reported residual deep supervision network for segmentation of PDAC was applied to segment pancreas using CT images of potential renal donors (normal pancreas) and patients with suspected PDAC (abnormal pancreas). Accuracy of DNN pancreas segmentation was assessed using DICE simulation coefficient (DSC), average symmetric surface distance (ASSD), and Hausdorff distance 95% percentile (HD95) as compared to manual segmentation. Furthermore, two radiologists semi-quantitatively assessed local accuracies and estimated volume of correctly segmented pancreas., Results: Forty-two normal and 49 abnormal CTs were assessed. Average DSC was 87.4 ± 3.1% and 85.5 ± 3.2%, ASSD 0.97 ± 0.30 and 1.34 ± 0.65, HD95 4.28 ± 2.36 and 6.31 ± 6.31 for normal and abnormal pancreas, respectively. Semi-quantitatively, ≥95% of pancreas volume was correctly segmented in 95.2% and 53.1% of normal and abnormal pancreas by both radiologists, and 97.6% and 75.5% by at least one radiologist. Most common segmentation errors were made on pancreatic and duodenal borders in both groups, and related to pancreatic tumor including duct dilatation, atrophy, tumor infiltration and collateral vessels., Conclusion: Pancreas DNN segmentation is accurate in a majority of cases, however, minor manual editing may be necessary; particularly in abnormal pancreas., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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43. Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer.
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Stoop TF, Theijse RT, Seelen LWF, Groot Koerkamp B, van Eijck CHJ, Wolfgang CL, van Tienhoven G, van Santvoort HC, Molenaar IQ, Wilmink JW, Del Chiaro M, Katz MHG, Hackert T, and Besselink MG
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- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Deoxycytidine therapeutic use, Deoxycytidine adverse effects, Gemcitabine, Pancreas, Neoadjuvant Therapy, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms surgery
- Abstract
Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda., (© 2023. Springer Nature Limited.)
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- 2024
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44. Machine learning to detect the SINEs of cancer.
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Douville C, Lahouel K, Kuo A, Grant H, Avigdor BE, Curtis SD, Summers M, Cohen JD, Wang Y, Mattox A, Dudley J, Dobbyn L, Popoli M, Ptak J, Nehme N, Silliman N, Blair C, Romans K, Thoburn C, Gizzi J, Schoen RE, Tie J, Gibbs P, Ho-Pham LT, Tran BNH, Tran TS, Nguyen TV, Goggins M, Wolfgang CL, Wang TL, Shih IM, Lennon AM, Hruban RH, Bettegowda C, Kinzler KW, Papadopoulos N, Vogelstein B, and Tomasetti C
- Subjects
- Humans, Reproducibility of Results, Short Interspersed Nucleotide Elements, Machine Learning, Aneuploidy, Neoplasms diagnosis, Neoplasms genetics
- Abstract
We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer. Samples from patients with cancer and controls were prespecified into four cohorts used for model training, analyte integration, and threshold determination, validation, and reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types in the validation cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and eight common protein biomarkers detected 51% of the cancers at 98.9% specificity. We found that part of the power of A-PLUS could be ascribed to a single feature-the global reduction of AluS subfamily elements in the circulating DNA of patients with solid cancer. We confirmed this reduction through the analysis of another independent dataset obtained with a different approach (whole-genome sequencing). The evaluation of Alu elements may therefore have the potential to enhance the performance of several methods designed for the earlier detection of cancer.
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- 2024
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45. Anatomical and Biological Considerations to Determine Resectability in Pancreatic Cancer.
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Rompen IF, Habib JR, Wolfgang CL, and Javed AA
- Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains associated with poor outcomes with a 5-year survival of 12% across all stages of the disease. These poor outcomes are driven by a delay in diagnosis and an early propensity for systemic dissemination of the disease. Recently, aggressive surgical approaches involving complex vascular resections and reconstructions have become more common, thus allowing more locally advanced tumors to be resected. Unfortunately, however, even after the completion of surgery and systemic therapy, approximately 40% of patients experience early recurrence of disease. To determine resectability, many institutions utilize anatomical staging systems based on the presence and extent of vascular involvement of major abdominal vessels around the pancreas. However, these classification systems are based on anatomical considerations only and do not factor in the burden of systemic disease. By integrating the biological criteria, we possibly could avoid futile resections often associated with significant morbidity. Especially patients with anatomically resectable disease who have a heavy burden of radiologically undetected systemic disease most likely do not derive a survival benefit from resection. On the contrary, we could offer complex resections to those who have locally advanced or oligometastatic disease but have favorable systemic biology and are most likely to benefit from resection. This review summarizes the current literature on defining anatomical and biological resectability in patients with pancreatic cancer.
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- 2024
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46. Accurate non-invasive grading of nonfunctional pancreatic neuroendocrine tumors with a CT derived radiomics signature.
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Javed AA, Zhu Z, Kinny-Köster B, Habib JR, Kawamoto S, Hruban RH, Fishman EK, Wolfgang CL, He J, and Chu LC
- Subjects
- Male, Humans, Female, Middle Aged, Aged, Retrospective Studies, Neoplasm Grading, Radiomics, Tomography, X-Ray Computed, Neuroendocrine Tumors diagnostic imaging, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms pathology, Neuroectodermal Tumors, Primitive
- Abstract
Purpose: The purpose of this study was to develop a radiomics-signature using computed tomography (CT) data for the preoperative prediction of grade of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs)., Materials and Methods: A retrospective study was performed on patients undergoing resection for NF-PNETs between 2010 and 2019. A total of 2436 radiomic features were extracted from arterial and venous phases of pancreas-protocol CT examinations. Radiomic features that were associated with final pathologic grade observed in the surgical specimens were subjected to joint mutual information maximization for hierarchical feature selection and the development of the radiomic-signature. Youden-index was used to identify optimal cutoff for determining tumor grade. A random forest prediction model was trained and validated internally. The performance of this tool in predicting tumor grade was compared to that of EUS-FNA sampling that was used as the standard of reference., Results: A total of 270 patients were included and a fusion radiomic-signature based on 10 selected features was developed using the development cohort (n = 201). There were 149 men and 121 women with a mean age of 59.4 ± 12.3 (standard deviation) years (range: 23.3-85.0 years). Upon internal validation in a new set of 69 patients, a strong discrimination was observed with an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.71-0.90) with corresponding sensitivity and specificity of 87.5% (95% CI: 79.7-95.3) and 73.3% (95% CI: 62.9-83.8) respectively. Of the study population, 143 patients (52.9%) underwent EUS-FNA. Biopsies were non-diagnostic in 26 patients (18.2%) and could not be graded due to insufficient sample in 42 patients (29.4%). In the cohort of 75 patients (52.4%) in whom biopsies were graded the radiomic-signature demonstrated not different AUC as compared to EUS-FNA (AUC: 0.69 vs. 0.67; P = 0.723), however greater sensitivity (i.e., ability to accurately identify G2/3 lesion was observed (80.8% vs. 42.3%; P < 0.001)., Conclusion: Non-invasive assessment of tumor grade in patients with PNETs using the proposed radiomic-signature demonstrated high accuracy. Prospective validation and optimization could overcome the commonly experienced diagnostic uncertainty in the assessment of tumor grade in patients with PNETs and could facilitate clinical decision-making., Competing Interests: Declaration of Competing Interest The authors do not have any conflict of interest to disclose in relation with this article., (Copyright © 2023. Published by Elsevier Masson SAS.)
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- 2024
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47. Concepts and techniques for revascularization of replaced hepatic arteries in pancreatic head resections.
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Floortje van Oosten A, Al Efishat M, Habib JR, Kinny-Köster B, Javed AA, He J, Fishman EK, Quintus Molenaar I, and Wolfgang CL
- Abstract
Background: The relationship of pancreatic ductal adenocarcinoma (PDAC) to important peripancreatic vasculature dictates resectability. As per the current guidelines, tumors with extensive, unreconstructible venous or arterial involvement are staged as unresectable locally advanced pancreatic cancer (LAPC). The introduction of effective multiagent chemotherapy and development of surgical techniques, have renewed interest in local control of PDAC. High-volume centers have demonstrated safe resection of short-segment encasement of the common hepatic artery. Knowledge of the unique anatomy of the patient's vasculature is important in surgical planning of these complex resections. Hepatic artery anomalies are common and insufficient knowledge can result in iatrogenic vascular injury during surgery., Methods and Results: Here, we discuss different strategies to resect and reconstruct replaced hepatic arteries during pancreatectomy for PDAC to ensure restoration of adequate blood flow to the liver. Strategies include various arterial transpositions, in-situ interposition grafts and the use of extra-anatomic jump grafts., Conclusion: These surgical techniques allow more patients to undergo the only available curative treatment currently available for PDAC. Moreover, these improvements in surgical techniques highlight the shortcoming of current resectability criteria, which rely mainly on local tumor involvement and technical resectability, and disregards tumor biology., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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48. "Conversion surgery" for locally advanced pancreatic cancer: A position paper by the study group at the joint meeting of the International Association of Pancreatology (IAP) & Japan Pancreas Society (JPS) 2022.
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Oba A, Del Chiaro M, Fujii T, Okano K, Stoop TF, Wu YHA, Maekawa A, Yoshida Y, Hashimoto D, Sugawara T, Inoue Y, Tanabe M, Sho M, Sasaki T, Takahashi Y, Matsumoto I, Sasahira N, Nagakawa Y, Satoi S, Schulick RD, Yoon YS, He J, Jang JY, Wolfgang CL, Hackert T, Besselink MG, Takaori K, and Takeyama Y
- Subjects
- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Japan, Neoadjuvant Therapy methods, Gastroenterology, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms surgery
- Abstract
Locally advanced pancreatic cancer (LAPC), which progresses locally and surrounds major vessels, has historically been deemed unresectable. Surgery alone failed to provide curative resection and improve overall survival. With the advancements in treatment, reports have shown favorable results in LAPC after undergoing successful chemotherapy therapy or chemoradiation therapy followed by surgical resection, so-called "conversion surgery", at experienced high-volume centers. However, recognizing significant regional and institutional disparities in the management of LAPC, an international consensus meeting on conversion surgery for LAPC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of Japan Pancreas Society (JPS) in Kyoto in July 2022. During the meeting, presenters reported the current best multidisciplinary practices for LAPC, including preoperative modalities, best systemic treatment regimens and durations, procedures of conversion surgery with or without vascular resections, biomarkers, and genetic studies. It was unanimously agreed among the experts in this meeting that "cancer biology is surpassing locoregional anatomical resectability" in the era of effective multiagent treatment. The biology of pancreatic cancer has yet to be further elucidated, and we believe it is essential to improve the treatment outcomes of LAPC patients through continued efforts from each institution and more international collaboration. This article summarizes the agreement during the discussion amongst the experts in the meeting. We hope that this will serve as a foundation for future international collaboration and recommendations for future guidelines., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)
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- 2023
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49. Predicting post-recurrence survival for patients with pancreatic cancer recurrence after primary resection: A Bi-institutional validated risk classification.
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van Oosten AF, Daamen LA, Groot VP, Biesma NC, Habib JR, van Goor IWJM, Kinny-Köster B, Burkhart RA, Wolfgang CL, van Santvoort HC, He J, and Molenaar IQ
- Subjects
- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoplasm Recurrence, Local pathology, Prognosis, Pancreatectomy methods, Retrospective Studies, Pancreatic Neoplasms, Pancreatic Neoplasms pathology, Carcinoma, Pancreatic Ductal pathology
- Abstract
Background: Over 80% of patients will develop disease recurrence after radical resection of pancreatic ductal adenocarcinoma (PDAC). This study aims to develop and validate a clinical risk score predicting post-recurrence survival (PRS) at time of recurrence., Methods: All patients who had recurrence after undergoing pancreatectomy for PDAC at the Johns Hopkins Hospital or at the Regional Academic Cancer Center Utrecht during the study period were included. Cox proportional hazard model was used to develop the risk model. Performance of the final model was assessed in a test set after internal validation., Results: Of 718 resected PDAC patients, 72% had recurrence after a median follow-up of 32 months. The median overall survival was 21 months and the median PRS was 9 months. Prognostic factors associated with shorter PRS were age (hazard ratio [HR] 1.02; 95% confidence interval [95%CI] 1.00-1.04), multiple-site recurrence (HR 1.57; 95%CI 1.08-2.28), and symptoms at time of recurrence (HR 2.33; 95%CI 1.59-3.41). Recurrence-free survival longer than 12 months (HR 0.55; 95%CI 0.36-0.83), FOLFIRINOX and gemcitabine-based adjuvant chemotherapy (HR 0.45; 95%CI 0.25-0.81; HR 0.58; 95%CI 0.26-0.93, respectively) were associated with a longer PRS. The resulting risk score had a good predictive accuracy (C-index: 0.73)., Conclusion: This study developed a clinical risk score based on an international cohort that predicts PRS in patients who underwent surgical resection for PDAC. This risk score will become available on www.evidencio.com and can help clinicians with patient counseling on prognosis., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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50. Demystifying BRAF Mutation Status in Colorectal Liver Metastases : A Multi-institutional, Collaborative Approach to 6 Open Clinical Questions.
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Margonis GA, Boerner T, Bachet JB, Buettner S, Moretto R, Andreatos N, Sartore-Bianchi A, Wang J, Kamphues C, Gagniere J, Lonardi S, Løes IM, Wagner D, Spallanzani A, Sasaki K, Burkhart R, Pietrantonio F, Pikoulis E, Pawlik TM, Truant S, Orlandi A, Pikouli A, Pella N, Beyer K, Poultsides G, Seeliger H, Aucejo FN, Kornprat P, Kaczirek K, Lønning PE, Kreis ME, Wolfgang CL, Weiss MJ, Cremolini C, Benoist S, and D'Angelica M
- Subjects
- Humans, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins p21(ras) genetics, Prognosis, Hepatectomy methods, Mutation, Colorectal Neoplasms pathology, Liver Neoplasms genetics, Liver Neoplasms surgery, Liver Neoplasms secondary
- Abstract
Objective: To investigate the clinical implications of BRAF -mutated (mut BRAF ) colorectal liver metastases (CRLMs)., Background: The clinical implications of mut BRAF status in CRLMs are largely unknown., Methods: Patients undergoing resection for mut BRAF CRLM were identified from prospectively maintained registries of the collaborating institutions. Overall survival (OS) and recurrence-free survival (RFS) were compared among patients with V600E versus non-V600E mutations, KRAS/BRAF comutation versus mut BRAF alone, microsatellite stability status (Microsatellite Stable (MSS) vs instable (MSI-high)), upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy versus nonoperative management., Results: A total of 240 patients harboring BRAF -mutated tumors were included. BRAF V600E mutation was associated with shorter OS (30.6 vs 144 mo, P =0.004), but not RFS compared with non-V600E mutations. KRAS/BRAF comutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs 26 mo, P <0.001) but not OS (33.5 vs 41 mo, P =0.3) compared with MSI-high tumors, whereas patients with resected converted disease had slightly worse RFS (8 vs 11 mo, P =0.01) and similar OS (30 vs 40 mo, P =0.4) compared with those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared with those with liver-limited disease (8.8 vs 40 mo, P <0.001). Repeat hepatectomy after intrahepatic recurrence was associated with improved OS compared with nonoperative management (41 vs 18.7 mo, P =0.004). All results continued to hold true in the multivariable OS analysis., Conclusions: Although surgery may be futile in patients with BRAF -mutated CRLM and concurrent extrahepatic disease, resection of converted disease resulted in encouraging survival in the absence of extrahepatic spread. Importantly, second hepatectomy in select patients with recurrence was associated with improved outcomes. Finally, MSI-high status identifies a better prognostic group, with regard to RFS while patients with non-V600E mutations have excellent prognosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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