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Introduction: Pancreatic Ductal Adenocarcinoma (PDA) is one of the most aggressive malignancies with a 5-year survival rate of 13%. Less than 20% of patients have a resectable tumor at diagnosis due to the lack of distinctive symptoms and reliable biomarkers. PDA is resistant to chemotherapy (CT) and understanding how to gain an anti-tumor effector response following stimulation is, therefore, critical for setting up an effective immunotherapy., Methods: Proliferation, and cytokine release and TCRB repertoire of from PDA patient peripheral T lymphocytes, before and after CT, were analyzed in vitro in response to four tumor-associated antigens (TAA), namely ENO1, FUBP1, GAPDH and K2C8. Transcriptional state of PDA patient PBMC was investigated using RNA-Seq before and after CT., Results: CT increased the number of TAA recognized by T lymphocytes, which positively correlated with patient survival, and high IFN-γ production TAA-induced responses were significantly increased after CT. We found that some ENO1-stimulated T cell clonotypes from CT-treated patients were expanded or de-novo induced, and that some clonotypes were reduced or even disappeared after CT. Patients that showed a higher number of effector responses to TAA (high IFN-γ/IL-10 ratio) after CT expressed increased fatty acid-related transcriptional signature. Conversely, patients that showed a higher number of regulatory responses to TAA (low IFN-γ/IL-10 ratio) after CT significantly expressed an increased IRAK1/IL1R axis-related transcriptional signature., Conclusion: These data suggest that the expression of fatty acid or IRAK1/IL1Rrelated genes predicts T lymphocyte effector or regulatory responses to TAA in patients that undergo CT. These findings are a springboard to set up precision immunotherapies in PDA based on the TAA vaccination in combination with CT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Brugiapaglia, Bulfamante, Curcio, Arigoni, Calogero, Bonello, Genuardi, Spadi, Satolli, Campra, Giordano, Cappello, Cordero and Novelli.)

Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis due to a lack of early diagnostic markers and effective therapy. In PDA patients, the glycolytic enzyme and plasminogen receptor alpha-enolase (ENO1) and the transcription factor far upstream element-binding protein 1 (FUBP1) are upregulated and elicit the production of autoantibodies (aAb) that discriminate healthy subjects from PDA patients, with the latter mostly directed to post-translational phosphorylated isoforms. Here, the correlation of prognosis with circulating ENO1 and FUBP1aAb, and their protein tissue expression was analyzed in PDA patients. Circulating ENO1 and FUBP1 aAb was analyzed in two cohorts of PDA patients by ELISA (n = 470), while tissues expression was observed by immunohistochemistry (n = 45). Overall survival (OS) was estimated using the Kaplan-Meier method, while the Cox model was used to estimate the hazard ratios (HR) adjusted for the main prognostic factors. Logistic models were applied to assess associations between death and its risk indicators. All statistical analyses were performed with Stata version 15. Unlike ENO1 aAb, there was a significant correlation between FUBP1 aAb and FUBP1 expression in tumors (p = 0.0268). In addition, we found that high ENO1 (p = 0.016) and intermediate FUBP1 aAb levels (p = 0.013) were unfavorable prognostic factors. Notably, it was found that high anti-FUBP1 aAb level is a good prognostic marker for tail-body PDA (p = 0.016). Our results suggest that different levels of circulating aAb to ENO1 and FUBP1 predict a poor outcome in PDA patients and can be used to improve therapeutic strategies., (© 2023. The Author(s).)

Objectives: To determine the reproducibility of the National Comprehensive Cancer Network (NCCN) resectability status classification for pancreatic cancer., Background: The NCCN classification defines 3 resectability classes (resectable, borderline resectable, locally advanced), according to vascular invasion. It is used to recommend different approaches and stratify patients during clinical trials., Methods: Prospective, multicenter, observational study (trial ID: NCT03673423). Main outcome measure was the interobserver agreement of tumor assignment to different resectability classes and quantification of vascular invasion degrees. Agreement was measured by Fleiss' k (k = 1 perfect agreement; k = 0 agreement by chance). Sixty-nine computed tomography (CT) scans of pathologically confirmed pancreatic adenocarcinoma were independently reviewed in a blinded fashion by 22 observers from 11 hospitals (11 surgeons and 11 radiologists). Rating differences between surgeons or radiologists and between hospitals with different volumes (≥60 or <60 resections/year) were assessed., Results: Complete agreement among 22 observers was recorded in 5 CT scans (7.2%), whereas 25 CT scans (36.2%) were variously assigned to all 3 resectability classes. Interobserver agreement varied from fair to moderate (Fleiss' k range: 0.282-0.555), with the lowest agreement for borderline resectable tumors. Assessing vascular contact ≤180° had the lowest agreement for all vessels (k range: 0.196-0.362). The highest concordance was recorded for venous invasion >180° (k range: 0.619-0.756). Neither reviewers' specialty nor hospital volume influenced the agreement., Conclusions: There is high variability in the assignment to resectability categories, which may compromise the reliability of treatments recommendations and the evidence of trials stratifying patients in resectability classes. Criteria should be revised to allow a reproducible classification., Competing Interests: Disclosure: The authors declare that they have nothing to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Heat shock protein 27 (HSP27), an intracellular molecular chaperone, is involved in the pathogenesis of cancer by promoting both tumor cell proliferation and resistance to therapy. HSP27 is also present in the circulation and circulating HSP27 (sHSP27) can elicit an autoimmune response with production of antibodies. Levels of sHSP27 are enhanced in patients with hepatocellular carcinoma (HCC); it is, however, unknown whether changes in HSP27 antibody levels occur in patients with HCC and can be exploited as a circulating biomarker of HCC. Our aim was to assess the potential association between newly diagnosed HCC and serum anti-HSP27 antibody levels. In this cross-sectional study, anti-HSP27 antibody levels were measured in serum samples from 71 HCC patients, 80 subjects with chronic liver disease, and 38 control subjects by immunoenzymatic assay. Anti-HSP27 antibody levels did not differ significantly among groups. However, in patients with chronic active hepatitis/cirrhosis, anti-HSP27 levels were significantly higher in subjects with a positive history of alcoholism (p = 0.03). Our data do not support the hypothesis that anti-HSP27 antibody levels may help identify patients with HCC among subjects with chronic liver disease. However, our finding that alcohol-related liver disease is associated with higher anti-HSP27 levels is novel and deserves further investigations.

Background: Pancreatic metastases from renal-cell carcinoma (RCC-PMs) are rare. Surgery may play a role in improving overall (OS) and disease-free survival (DFS)., Methods: Clinical-pathological features, surgery and follow-up data of patients with RCC-PMs operated on in three pancreatic surgical centers (2000-2019) were retrospectively evaluated., Results: Thirty-nine patients (21 male/18 female, averaging 65 years) were enrolled. RCC-PMs were metachronous in 36 patients (mean 94 months, up to 24 years after nephrectomy), multiple in 21 patients, and with a median size of 2.5 (range, 0.7-7.5) cm. All the patients underwent pancreatic surgery (33 standard resections, 6 limited resections). Fifteen patients had post-operative complications (morbidity 38.5%). The median DFS was 63 months, and 19 out of 36 patients showed a disease recurrence. The median OS was 134 months, and 13 out of 36 patients were alive with no evidence of disease. At univariate analysis, lymph node positivity (HR 5.1, 95% CI 1.5-18), multi-visceral resection (HR 3.4, 95% CI 1.1-10) and synchronous RCC-PMs (HR 13, 95% CI 3-55) were significantly associated with a short OS., Conclusion: Surgery may allow a DFS up to 17 years in more than one third of patients, even after limited resections. Splenectomy and lymph node dissection are not mandatory.

The aim of this study is to evaluate the role of age after pancreaticoduodenectomy. This is a retrospective study of 223 patients who underwent pancreaticoduodenectomy for periampullary diseases. Three age groups of patients were compared: ≤70 years of age (group A); between 71 and 79 years of age (group B) and 80 years of age or older (group C). The primary endpoint was the postoperative mortality rate. Secondary endpoints were the overall postoperative morbidity, postoperative pancreatic fistula, postoperative pancreatic haemorrhage, bile leakage, delayed gastric emptying rates, the length of hospital stay, intensive care unit stay, the type of discharge from hospital, reoperation rate and overall survival. Uni-multivariate analyses and Kaplan-Meier curve were carried out. At univariate analysis, only the type of discharge from hospital showed that group B and C patients required a period of rehabilitation more frequently than group A (P = 0.047 and P < 0.001, respectively). Multivariate analysis confirmed that age was not related to postoperative mortality (P = 0.258), morbidity (P = 0.912) and overall survival (P = 0.658), but it was related to type of discharge (P < 0.001). The present study seems to suggest that a pancreaticoduodenectomy is a feasible and safe procedure, even in elderly and very elderly patients even if the latter require a longer period of rehabilitation.

This Position Paper contains clinically oriented guidelines by the Italian Association for the Study of the Pancreas (AISP) for the diagnosis and treatment of severe acute pancreatitis. The statements were formulated by three working groups of experts who searched and analysed the most recent literature; a consensus process was then performed using a modified Delphi procedure. The statements provide recommendations on the most appropriate definition of the complications of severe acute pancreatitis, the diagnostic approach and the timing of conservative as well as interventional endoscopic, radiological and surgical treatments., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aim: Distal pancreatectomies (DP) are associated with high risk of postoperative complications, and in many series higher morbidity rate than duodenopancreatectomies has been reported. To evaluate the role of a collagen sponge with human fibrinogen and thrombin film (TachoSil®) in limiting the incidence of complications after DP., Methods: From 1996 to 2013, 221 patients have been submitted to distal pancreatectomy (± splenectomy) in our Division. A retrospective analysis has been conducted in a group of 36 consecutive and prospectively collected DP treated with intraoperative placement of TachoSil® on pancreatic stump from 2010 to 2013 (group 1). A control series of 36 consecutive patients (group 2) was matched 1:1 from hystorical database. The variables considered in the analysis were: age, gender, ASA score, pancreatic texture (hard vs. soft), histology, operative time, postoperative mortality, morbility (postoperative pancreatic fistula - POPF, postoperative hemorrage - PPH, delayed gastric emptying - DGE) and hospital stay. Differences between POPF, PPH, DGE and hospital stays between grops were investigated with χ² and t-Student test. Univariate analysis was conducted to determine factors related to POPF development. Statistical analysis was performed using freeware Microsoft Excel based program., Results: Post operative mortality was 0% in both groups. POPF were registered in 36.1% (13/36) and 41.6 % (15/36) in groups 1 and 2, respectively (P=n.s.); in group 1 we didn't observe grade C POPF, while 4 patients in control group developed grade C POPF (P<0,05). No differences were found between two groups in terms of incidence of PPH and DGE. The median duration of postoperative hospital stay in group 1 was 21.8 (7-189) days compared with 31.13 (9-249) days in group 2 (P<0.001)., Conclusion: The use of TachoSil® seems to be associated with lower incidence of grade C POPF but larger controlled trials are needed to surely assess the usefulness of TachoSil® in pancreatic surgery in order to reduce pancreatic specific complications and their severity.

Introduction: Autoimmune pancreatitis (AIP) is a rare pancreatic disorder among chronic pancreatitis that can mimick pancreatic cancer (PC). Patients with type 1 AIP usually present obstructive jaundice associated with high level of IgG4 in serum and a pancreatic mass at radiological imaging; these disorders may be associated with other organs lesions presenting the same histopathological features, and in these cases AIP should be considered a pancreatic localization of an IgG4-related systemic disease., Presentation of Case: We report the case of a young man with initial suspect of PC to be treated with surgery, and final diagnosis of AIP in the context of an IgG4-related systemic disease., Discussion: Because of its similar features, several algorithms have been proposed for AIP diagnosis, based on combination of clinical/serological and radiological criteria. However, histology represents the only way to obtain definitive diagnosis, even if sometimes it is difficult to obtain biological samples., Conclusion: IgG4-related systemic disease must be taken into account among differential diagnosis during the workup for PC, in order to avoid unnecessary surgery., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)