@article{Maggino2023207,

title = {CA19.9 Response and Tumor Size Predict Recurrence Following Post-neoadjuvant Pancreatectomy in Initially Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma},

author = {Laura Maggino and Giuseppe Malleo and Stefano Crippa and Giulio Belfiori and Sara Nobile and Giulia Gasparini and Gabriella Lionetto and Claudio Luchini and Paola Mattiolo and Marco Schiavo-Lena and Claudio Doglioni and Aldo Scarpa and Claudio Bassi and Massimo Falconi and Roberto Salvia},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85139743479&doi=10.1245%2fs10434-022-12622-w&partnerID=40&md5=37a355ed15c5f8bfc23e130604180fe8},

doi = {10.1245/s10434-022-12622-w},

issn = {10689265},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Annals of Surgical Oncology},

volume = {30},

number = {1},

pages = {207 – 219},

publisher = {Springer Science and Business Media Deutschland GmbH},

abstract = {Background: Data on recurrence after post-neoadjuvant pancreatectomy are scant. This study investigated the incidence and pattern of recurrence in patients with initially resectable and borderline resectable pancreatic ductal adenocarcinoma who received post-neoadjuvant pancreatectomy. Furthermore, preoperative predictors of recurrence-free survival (RFS) and their interactions were determined. Patients and Methods: Patients undergoing post-neoadjuvant pancreatectomy at two academic facilities between 2013 and 2017 were analyzed using standard statistics. The possible interplay between preoperative parameters was scrutinized including interaction terms in multivariable Cox models. Results: Among 315 included patients, 152 (48.3%) were anatomically resectable. The median RFS was 15.7 months, with 1- and 3-year recurrence rates of 41.9% and 74.2%, respectively. Distant recurrence occurred in 83.3% of patients, with lung-only patterns exhibiting the most favorable prognostic outlook. Normal posttreatment CA19.9, ΔCA19.9 (both in patients with normal and elevated baseline levels), and posttreatment tumor size were associated with RFS. Critical thresholds for ΔCA19.9 and tumor size were set at 50% and 20 mm, respectively. Interaction between ΔCA19.9 and posttreatment CA19.9 suggested a significant risk reduction in patients with elevated values when ΔCA19.9 exceeded 50%. Moreover, posttreatment tumor size interacted with posttreatment CA19.9 and ΔCA19.9, suggesting an increased risk in the instance of elevated posttreatment CA19.9 values and a protective effect associated with CA19.9 response in patients with tumor size >20 mm. Conclusion: Recurrence following post-neoadjuvant pancreatectomy is common. Preoperative tumor size <20 mm, normal posttreatment CA19.9 and ΔCA19.9 > 50% were associated with longer RFS. These variables should not be taken in isolation, as their interaction significantly modulates the recurrence risk. © 2022, The Author(s).},

note = {Cited by: 1; All Open Access, Green Open Access, Hybrid Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Takahashi2022E510,

title = {Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-label Multicenter Prospective Trial (JASPAC05)},

author = {Shinichiro Takahashi and Izumi Ohno and Masafumi Ikeda and Masaru Konishi and Tatsushi Kobayashi and Tetsuo Akimoto and Motohiro Kojima and Soichiro Morinaga and Hirochika Toyama and Yasuhiro Shimizu and Atsushi Miyamoto and Moriaki Tomikawa and Norihisa Takakura and Wataru Takayama and Satoshi Hirano and Takehito Otsubo and Masato Nagino and Wataru Kimura and Keishi Sugimachi and Katsuhiko Uesaka},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85139571403&doi=10.1097%2fSLA.0000000000004535&partnerID=40&md5=c1aa99be218b6cfe07848d2dd18b3598},

doi = {10.1097/SLA.0000000000004535},

issn = {00034932},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Annals of Surgery},

volume = {276},

number = {5},

pages = {E510 – E517},

publisher = {Wolters Kluwer Health},

abstract = {Objective: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in BRPC. Summary of Background Data: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established. Methods: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m2 bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a 1-sided α = 0.05 and β = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively. Results: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively. Conclusions: S-1 and concurrent radiotherapy seem to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.},

note = {Cited by: 15},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Yamaguchi20221043,

title = {Results of a Phase II Study on the Use of Neoadjuvant Chemotherapy (FOLFIRINOX or GEM/nab-PTX) for Borderline-resectable Pancreatic Cancer (NUPAT-01)},

author = {Junpei Yamaguchi and Yukihiro Yokoyama and Tsutomu Fujii and Suguru Yamada and Hideki Takami and Hiroki Kawashima and Eizaburo Ohno and Takuya Ishikawa and Osamu Maeda and Hiroshi Ogawa and Yasuhiro Kodera and Masato Nagino and Tomoki Ebata},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85131108074&doi=10.1097%2fSLA.0000000000005430&partnerID=40&md5=70120cfb2fbb9a0715bafde548ac56cb},

doi = {10.1097/SLA.0000000000005430},

issn = {00034932},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Annals of Surgery},

volume = {275},

number = {6},

pages = {1043 – 1049},

publisher = {Lippincott Williams and Wilkins},

abstract = {Objective:Given the frequent adverse events with multidrug chemotherapy, not only the survival benefit but also the feasibility of using neoadjuvant chemotherapy to treat pancreatic cancer need to be clarified.Summary of Background Data:Although the development of multidrug chemotherapy regimens has improved the survival outcomes of patients with unresectable pancreatic cancer, the benefits of these treatments in the neo-adjuvant setting remain controversial.Methods:Patients with borderline-resectable pancreatic cancer were enrolled and randomly assigned to receive neoadjuvant chemotherapy with either FOLFIRINOX or gemcitabine with nab-paclitaxel (GEM/nab-PTX). After the completion of chemotherapy, patients underwent surgical resection when feasible. This study (NUPAT-01) was a randomized phase II trial, and the primary endpoint was the R0 resection rate.Results:Fifty-one patients were enrolled in this study [FOLFIRINOX (n = 26) and GEM/nab-PTX (n = 25)]. A total of 84.3% (n = 43/51) of the patients eventually underwent surgery, and R0 resection was achieved in 67.4% (n = 33/ 51) of the patients. Adverse events (grade >3) due to neoadjuvant treatment were observed in 45.1% of the patients (n = 23/51), and major surgical complications occurred in 30.0% (n = 13/43), with no mortality noted. The intention-to-treat analysis showed that the 3-year overall survival rate was 54.7%, with a median survival time of 39.4 months, and a significant difference in overall survival was not observed between the FOLFIRINOX and GEM/nab-PTX groups.Conclusions:These results indicate that neoadjuvant chemotherapy with FOLFIRINOX or GEM/nab-PTX is feasible and well tolerated, achieving an R0 resection rate of 67.4%. The survival of patients was even found to be favorable in the intention-to-treat analysis. © 2022 Lippincott Williams and Wilkins. All rights reserved.},

note = {Cited by: 2},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{GHANEH2022,

title = {Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial},

author = {Paula Ghaneh and Daniel Palmer and Silvia Cicconi and Richard Jackson and Christopher Michael Halloran and Charlotte Rawcliffe and Rajaram Sripadam and Somnath Mukherjee and Zahir Soonawalla and Jonathan Wadsley and Ahmed Al-Mukhtar and Euan Dickson and Janet Graham and Long Jiao and Harpreet S Wasan and Iain S Tait and Andreas Prachalias and Paul Ross and Juan W Valle and Derek A O'Reilly and Bilal Al-Sarireh and Sarah Gwynne and Irfan Ahmed and Kate Connolly and Kein-Long Yim and David Cunningham and Thomas Armstrong and Caroline Archer and Keith Roberts and Yuk Ting Ma and Christoph Springfeld and Christine Tjaden and Thilo Hackert and Markus W Büchler and John P Neoptolemos},

url = {https://www.sciencedirect.com/science/article/pii/S246812532200348X},

doi = {https://doi.org/10.1016/S2468-1253(22)00348-X},

issn = {2468-1253},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {The Lancet Gastroenterology & Hepatology},

abstract = {Summary 

Background 

Patients with borderline resectable pancreatic ductal adenocarcinoma have relatively low resection rates and poor survival despite the use of adjuvant chemotherapy. The aim of our study was to establish the feasibility and efficacy of three different types of short-course neoadjuvant therapy compared with immediate surgery. 

Methods 

ESPAC5 (formerly known as ESPAC-5f) was a multicentre, open label, randomised controlled trial done in 16 pancreatic centres in two countries (UK and Germany). Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, biopsy proven pancreatic ductal adenocarcinoma in the pancreatic head, and were staged as having a borderline resectable tumour by contrast-enhanced CT criteria following central review. Participants were randomly assigned by means of minimisation to one of four groups: immediate surgery; neoadjuvant gemcitabine and capecitabine (gemcitabine 1000 mg/m2 on days 1, 8, and 15, and oral capecitabine 830 mg/m2 twice a day on days 1–21 of a 28-day cycle for two cycles); neoadjuvant FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, folinic acid given according to local practice, and fluorouracil 400 mg/m2 bolus injection on days 1 and 15 followed by 2400 mg/m2 46 h intravenous infusion given on days 1 and 15, repeated every 2 weeks for four cycles); or neoadjuvant capecitabine-based chemoradiation (total dose 50·4 Gy in 28 daily fractions over 5·5 weeks [1·8 Gy per fraction, Monday to Friday] with capecitabine 830 mg/m2 twice daily [Monday to Friday] throughout radiotherapy). Patients underwent restaging contrast-enhanced CT at 4–6 weeks after neoadjuvant therapy and underwent surgical exploration if the tumour was still at least borderline resectable. All patients who had their tumour resected received adjuvant therapy at the oncologist's discretion. Primary endpoints were recruitment rate and resection rate. Analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN, 89500674, and is complete. 

Findings Between Sept 3, 2014, and Dec 20, 2018, from 478 patients screened, 90 were randomly assigned to a group (33 to immediate surgery, 20 to gemcitabine plus capecitabine, 20 to FOLFIRINOX, and 17 to capecitabine-based chemoradiation); four patients were excluded from the intention-to-treat analysis (one in the capecitabine-based chemoradiotherapy withdrew consent before starting therapy and three [two in the immediate surgery group and one in the gemcitabine plus capecitabine group] were found to be ineligible after randomisation). 44 (80%) of 55 patients completed neoadjuvant therapy. The recruitment rate was 25·92 patients per year from 16 sites; 21 (68%) of 31 patients in the immediate surgery and 30 (55%) of 55 patients in the combined neoadjuvant therapy groups underwent resection (p=0·33). R0 resection was achieved in three (14%) of 21 patients in the immediate surgery group and seven (23%) of 30 in the neoadjuvant therapy groups combined (p=0·49). Surgical complications were observed in 29 (43%) of 68 patients who underwent surgery; no patients died within 30 days. 46 (84%) of 55 patients receiving neoadjuvant therapy were available for restaging. Six (13%) of 46 had a partial response. Median follow-up time was 12·2 months (95% CI 12·0–12·4). 1-year overall survival was 39% (95% CI 24–61) for immediate surgery, 78% (60–100) for gemcitabine plus capecitabine, 84% (70–100) for FOLFIRINOX, and 60% (37–97) for capecitabine-based chemoradiotherapy (p=0·0028). 1-year disease-free survival from surgery was 33% (95% CI 19–58) for immediate surgery and 59% (46–74) for the combined neoadjuvant therapies (hazard ratio 0·53 [95% CI 0·28–0·98]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33914468,

title = {A Pretreatment Prognostic Score to Stratify Survival in Pancreatic Cancer},

author = {Thomas Hank and Ulf Hinz and Thomas Reiner and Giuseppe Malleo and Anna-Katharina König and Laura Maggino and Giovanni Marchegiani and Jörg Kaiser and Salvatore Paiella and Alessandra Binco and Roberto Salvia and Thilo Hackert and Claudio Bassi and Markus W Büchler and Oliver Strobel},

doi = {10.1097/SLA.0000000000004845},

issn = {1528-1140},

year  = {2021},

date = {2021-03-01},

urldate = {2021-03-01},

journal = {Ann Surg},

abstract = {OBJECTIVE: To develop and validate a pretreatment prognostic score in pancreatic cancer (PDAC).



BACKGROUND: Pretreatment prognostication in PDAC is important for treatment decisions but remains challenging. Available prognostic tools are derived from selected cohorts of patients who underwent resection, excluding up to 20% of patients with exploration only, and do not adequately reflect the pretreatment scenario.



METHODS: Patients undergoing surgery for PDAC in Heidelberg from 07/2006 to 06/2014 were identified from a prospective database. Pretreatment parameters were extracted from the database and the laboratory information system. Parameters independently associated with overall survival by uni- and multivariable analyses were used to build a prognostic score. A contemporary cohort from Verona was used for external validation.



RESULTS: In 1197 patients, multiple pretreatment parameters were associated with overall survival by univariable analyses. ASA-classification, CA19-9, CEA, CRP, albumin, and platelet count were independently associated with survival and were used to create the Heidelberg Prognostic Pancreatic Cancer (HELPP)-score. The HELPP-score was closely associated with overall survival (median survival between 31.3 and 4.8 months; 5-year survival rates between 35% and 0%) and was able to stratify survival in subgroups with or without resection as well as in CA19-9 non-secretors. In the resected subgroup the HELPP-score stratified survival independently of pathological prognostic factors. The HELPP-score was externally validated and was superior to CA19-9 in both the development and validation cohorts.



CONCLUSION: The HELPP-score is a readily available prognostic tool based on pretreatment routine parameters to stratify survival in PDAC independently of resection status and pathological tumor stage.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Magistri20211098,

title = {Robotic vs open distal pancreatectomy: A multi-institutional matched comparison analysis},

author = {Paolo Magistri and Ugo Boggi and Alessandro Esposito and Francesco Maria Carrano and Benedetta Pesi and Roberto Ballarin and Matteo De Pastena and Francesca Menonna and Luca Moraldi and Marcovalerio Melis and Andrea Coratti and Elliot Newman and Niccolò Napoli and Marco Ramera and Fabrizio Di Benedetto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85100356744&doi=10.1002%2fjhbp.881&partnerID=40&md5=862b4dfc5ade51d96a983412f564f6ea},

doi = {10.1002/jhbp.881},

issn = {18686974},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Journal of Hepato-Biliary-Pancreatic Sciences},

volume = {28},

number = {12},

pages = {1098 – 1106},

publisher = {John Wiley and Sons Inc},

abstract = {Background: Pancreatic surgery is still a challenge even in high-volume centers. Clinically relevant postoperative pancreatic fistula (CR-POPF) represents the greatest contributor to major morbidity and mortality, especially following pancreatic distal resection. In this study, we compared robotic distal pancreatectomy (RDP) to open distal pancreatectomy (ODP) in terms of CR-POPF development and analyzed oncologic efficacy of RDP in the subgroup of patients with pancreatic ductal adenocarcinoma (PDAC). Methods: We collected data from five high-volume centers for pancreatic surgery and performed a matched comparison analysis to compare short and long-term outcomes after ODP or RDP. Patients were matched with a 2:1 ratio according to age, ASA (American Society of Anesthesiologists) score, body mass index (BMI), final pathology, and TNM (Tumour, Node, Metastasis) staging system VIII ed. Results: Two hundred and forty-six patients who underwent 82 RDPs and 164 ODPs were included. No differences were found in the incidence of CR-POPF. In the PDAC group, median DFS and OS were 10.8 months and 14.8 months in the ODP group and 10.4 months and 15 months in the RDP group, respectively. Conclusions: Robotic distal pancreatectomy is a safe surgical strategy for PDAC and incidence of CR-POPF is equivalent between RDP and ODP. RDP should be considered equivalent to ODP in terms of oncological efficacy when performed in high-volume and proficient centers. © 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery},

note = {Cited by: 7},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Paolini2021,

title = {Robotic versus open pancreaticoduodenectomy: Is there any difference for frail patients?},

author = {Claudia Paolini and Lapo Bencini and Linda Gabellini and Irene Urciuoli and Sabrina Pacciani and Angela Tribuzi and Luca Moraldi and Massimo Calistri and Andrea Coratti},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85098989962&doi=10.1016%2fj.suronc.2020.12.009&partnerID=40&md5=710c149e71a9c671a504c3b950b49a93},

doi = {10.1016/j.suronc.2020.12.009},

issn = {09607404},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Surgical Oncology},

volume = {37},

publisher = {Elsevier Ltd},

abstract = {Background: Old age and frailty are predictors of early postoperative results after pancreatic surgery. We analysed the results of robotic and open pancreatoduodenectomy in elderly and frail patients. Methods: Data from the local robotic pancreatoduodenectomy database were reviewed and matched with those from open operations during the same period (2014–2020). Both old age and frailty were used to determine any correlation with postoperative outcomes. Elderly patients were defined as patients aged 70 years or more, while frailty was classified according to the validated modified Frailty Index. Results: A total of 118 pancreatoduodenectomies were included in the analysis: 65 (55.1%) robotic and 53 (44.9%) open. More than 50% of patients were frail. Overall, 7.6% of patients experienced grade IV Clavien-Dindo complications, and 3.4% died within 90 days after surgery. Frail patients experienced a similar rate of severe complications after robotic vs. open operations (5.3 vs. 11.6; p = 0.439) but earlier refeeding (3 days vs. 4 days; p = 0.006) and earlier drain removal (6 days vs. 7 days; p = 0.046) when operated on by a robotic approach. The oncological outcomes, including limphnodes retrieval, residual disease, recurrences, and survival, were not influenced by the surgical approach. Non-elderly patients also showed more benefits with the robotic approach (lower complication index, earlier refeeding, and drain removal). Conclusions: Robotic pancreatoduodenectomy is associated with risks of major complications that are comparable to those of open operation in frail patients. Some perioperative parameters (refeeding, drain removal) seem to favour robotics in frail patients and younger patients, although at the price of longer operating times. © 2021 Elsevier Ltd},

note = {Cited by: 3},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Okusaka2020326,

title = {Clinical Practice Guidelines for Pancreatic Cancer 2019 from the Japan Pancreas Society: A Synopsis},

author = {Takuji Okusaka and Masafumi Nakamura and Masahiro Yoshida and Masayuki Kitano and Katsuhiko Uesaka and Yoshinori Ito and Junji Furuse and Keiji Hanada and Kazuichi Okazaki},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85082094118&doi=10.1097%2fMPA.0000000000001513&partnerID=40&md5=2711a0bb237001a4c9b21c33e3fb8145},

doi = {10.1097/MPA.0000000000001513},

issn = {08853177},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Pancreas},

volume = {49},

number = {3},

pages = {326 – 335},

publisher = {Lippincott Williams and Wilkins},

abstract = {Objectives Clinical Practice Guidelines for Pancreatic Cancer were first published in 2006 by the Japan Pancreas Society, and they were revised in 2009, 2013, and 2016. In July 2019, the Clinical Practice Guidelines for Pancreatic Cancer 2019 were newly revised in Japanese. Methods For this version, we developed the new guidelines according to the Minds Manual for Guideline Development 2017, which includes the concepts of GRADE (Grading Recommendations Assessment, Development, and Evaluation), to enable a better understanding of the current guidelines. Results The guidelines show algorithms for the diagnosis, treatment, and chemotherapy of pancreatic cancer and address 7 subjects: diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy, stent therapy, and supportive and palliative medicine. They include 56 clinical questions and 84 statements. There are statements corresponding to clinical questions, evidence levels, recommendation strengths, and agreement rates. Conclusions These guidelines represent the most standard clinical and practical management guidelines at this time in Japan. This is the English synopsis of the Clinical Practice Guidelines for Pancreatic Cancer 2019 in Japanese and is an attempt to disseminate the Japanese guidelines worldwide for introducing the Japanese approach for clinical management of pancreatic cancer. © Wolters Kluwer Health, Inc. All rights reserved.},

note = {Cited by: 63; All Open Access, Green Open Access, Hybrid Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}