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Sökning: WFRF:(Del Chiaro Marco)

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1.
  • Bassi, Claudio, et al. (författare)
  • The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula : 11 Years After
  • 2017
  • Ingår i: Surgery. - : Elsevier BV. - 0039-6060 .- 1532-7361. ; 161:3, s. 584-591
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In 2005, the International Study Group of Pancreatic Fistula developed a definition and grading of postoperative pancreatic fistula that has been accepted universally. Eleven years later, because postoperative pancreatic fistula remains one of the most relevant and harmful complications of pancreatic operation, the International Study Group of Pancreatic Fistula classification has become the gold standard in defining postoperative pancreatic fistula in clinical practice. The aim of the present report is to verify the value of the International Study Group of Pancreatic Fistula definition and grading of postoperative pancreatic fistula and to update the International Study Group of Pancreatic Fistula classification in light of recent evidence that has emerged, as well as to address the lingering controversies about the original definition and grading of postoperative pancreatic fistula. Methods: The International Study Group of Pancreatic Fistula reconvened as the International Study Group in Pancreatic Surgery in order to perform a review of the recent literature and consequently to update and revise the grading system of postoperative pancreatic fistula. Results: Based on the literature since 2005 investigating the validity and clinical use of the original International Study Group of Pancreatic Fistula classification, a clinically relevant postoperative pancreatic fistula is now redefined as a drain output of any measurable volume of fluid with an amylase level >3 times the upper limit of institutional normal serum amylase activity, associated with a clinically relevant development/condition related directly to the postoperative pancreatic fistula. Consequently, the former "grade A postoperative pancreatic fistula" is now redefined and called a "biochemical leak," because it has no clinical importance and is no longer referred to a true pancreatic fistula. Postoperative pancreatic fistula grades B and C are confirmed but defined more strictly. In particular, grade B requires a change in the postoperative management; drains are either left in place >3 weeks or repositioned through endoscopic or percutaneous procedures. Grade C postoperative pancreatic fistula refers to those postoperative pancreatic fistula that require reoperation or lead to single or multiple organ failure and/or mortality attributable to the pancreatic fistula. Conclusion: This new definition and grading system of postoperative pancreatic fistula should lead to a more universally consistent evaluation of operative outcomes after pancreatic operation and will allow for a better comparison of techniques used to mitigate the rate and clinical impact of a pancreatic fistula. Use of this updated classification will also allow for more precise comparisons of surgical quality between surgeons and units who perform pancreatic surgery.
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2.
  • Siriwardena, Ajith K., et al. (författare)
  • Standards for reporting on surgery for chronic pancreatitis : a report from the International Study Group for Pancreatic Surgery (ISGPS)
  • 2020
  • Ingår i: Surgery (United States). - : Elsevier BV. - 0039-6060. ; 168:1, s. 101-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The International Study Group for Pancreatic Surgery provides globally accepted definitions for reporting of complications after pancreatic surgery. This International Study Group for Pancreatic Surgery project aims to provide a standardized framework for reporting of the results of operative treatment for chronic pancreatitis. Methods: An International Study Group for Pancreatic Surgery project circulation list was created with pre-existing and new members and including gastroenterologists in addition to surgeons. A computerized search of the literature was undertaken for articles reporting the operative treatment of chronic pancreatitis. The results of the literature search were presented at the first face-to-face meeting of this International Study Group for Pancreatic Surgery project group. A document outlining proposed reporting standards was produced by discussion during an initial meeting of the International Study Group for Pancreatic Surgery. An electronic questionnaire was then sent to all current members of the International Study Group for Pancreatic Surgery. Responses were collated and further discussed at international meetings in North America, Europe, and at the International Association of Pancreatology World Congress in 2019. A final consensus document was produced by integration of multiple iterations. Results: The International Study Group for Pancreatic Surgery consensus standards for reporting of surgery in chronic pancreatitis recommends 4 core domains and the necessary variables needed for reporting of results: clinical baseline before operation; the morphology of the diseased gland; a new, standardized, operative terminology; and a minimum outcome dataset. The 4 domains combine to give a comprehensive framework for reports. Conclusion: Adoption of the 4 domains of the International Study Group for Pancreatic Surgery reporting standards for surgery for chronic pancreatitis will facilitate comparison of results between centers and help to improve the care for patients with this debilitating disease.
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3.
  • van Hilst, Jony, et al. (författare)
  • Minimally Invasive versus Open Distal Pancreatectomy for Ductal Adenocarcinoma (DIPLOMA)
  • 2019
  • Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 269:1, s. 10-17
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC).Background: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC.Methods: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival.Results: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200 mL (60–400) vs 300 mL (150–500), P = 0.001] and hospital stay [8 (6–12) vs 9 (7–14) days, P < 0.001] were lower after MIDP. Clavien-Dindo grade ≥3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P > 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerota's fascia resection (31% vs 60%, P < 0.001) and lymph node retrieval [14 (8–22) vs 22 (14–31), P< 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22–34] versus 31 (95% CI, 26–36) months (P = 0.929).Conclusions: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.
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4.
  • Arnelo, Urban, et al. (författare)
  • Intraoperative pancreatoscopy can improve the detection of skip lesions during surgery for intraductal papillary mucinous neoplasia : a pilot study
  • 2023
  • Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 23:6, s. 704-711
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Intraoperative pancreatoscopy is a promising procedure that might guide surgical resection for suspected main duct (MD) and mixed type (MT) intraductal papillary mucinous neoplasms (IPMNs). The aim of the present study was to assess the diagnostic yield and clinical impact of intraoperative pancreatoscopy in patients operated on for MD and MT-IPMNs.Methods: This is a retrospective cohort study. Patients undergoing surgery for suspected MD or MT-IPMN underwent intraoperative pancreatoscopy and frozen section analysis. In all patients who required extended resection due to pancreatoscopic findings, we compared the final histology with the results of the intraoperative frozen section analysis.Results: In total, 46 patients, 48% females, mean age (range) 67 years (45–82 years) underwent intraoperative pancreatoscopy. No mortality or procedure related complications were observed. Pancreatoscopy changed the operative course in 30 patients (65%), leading to extended resections in 20 patients (43%) and to parenchyma sparing procedures in 10 patients (22%). Analyzing the group of patients who underwent extended resections, 7 (35%) displayed lesions that needed further surgical treatment (six high grade dysplasia and one with G1 pancreatic neuroendocrine tumor) and among those 7, just 1 (14%) would have been detected exclusively with histological frozen section analysis of the transection margin. The combination of both pancreatoscopy and frozen section analysis lead to 86% sensitivity and 92% specificity for the detection of pathological tissue in the remnant pancreas.Conclusion: Intraoperative pancreatoscopy is a safe and feasible procedure and might allow the detection of skip lesions during surgery for suspect MD-involving IPMNs.
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5.
  • Arnelo, Urban, et al. (författare)
  • Single-operator pancreatoscopy is helpful in the evaluation of suspected intraductal papillary mucinous neoplasms (IPMN)
  • 2014
  • Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 14:6, s. 510-514
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVE: Even when advanced cross-sectional imaging modalities have been employed, endoscopic evaluation of intraductal papillary mucinous neoplasms (IPMN) is often required in order to assess the final character and extent of lesions. The current study addresses the use of SpyGlass single-operator peroral pancreatoscopy in suspected IPMN.DESIGN: A prospective, non-randomized exploratory cohort study.SETTING: Single-center.PATIENTS AND INTERVENTION: A prospective study-cohort of 44 consecutive patients in a single tertiary referral center who underwent ERCP and peroral pancreatoscopy, was prospectively collected between July 2007 and March 2013 because of a radiological signs of IPMN. These IPMN-findings were discovered incidentally in 44% of the cases.MAIN OUTCOME MEASUREMENTS: Diagnostic accuracy (specificity & sensitivity) and complications.RESULTS: The targeted region of the pancreatic duct was reached with the SpyGlass system in 41 patients (median age 65 years, 41% female). Three patients were excluded from analysis because of failed deep cannulation of the pancreatic duct. Brush cytology was taken in 88% and direct biopsies in 41%. IPMN with intermediate or high-grade dysplasia was the main final diagnosis (76%) in 22 patients who had surgery. Out of the 17 patients with a final diagnosis of MD-IPMN, 76% were correctly identified by pancreatoscopy. Of the 9 patients with a final diagnosis of BD-IPMN, the pancreatoscopy identified 78% of the cases correctly.The incidence of post-ERCP pancreatitis was 17%. Pancreatoscopy was found to have provided additional diagnostic information in the vast majority of the cases and to affect clinical decision-making in 76%.LIMITATIONS: Single-center study.CONCLUSIONS: Single-operator peroral pancreatoscopy contributed to the clinical evaluation of IPMN lesions and influenced decision-making concerning their clinical management. The problem of post-procedural pancreatitis needs further attention.
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6.
  • Crippa, Stefano, et al. (författare)
  • A tug-of-war in intraductal papillary mucinous neoplasms management : Comparison between 2017 International and 2018 European guidelines
  • 2021
  • Ingår i: Digestive and Liver Disease. - : Elsevier. - 1590-8658 .- 1878-3562. ; 53:8, s. 998-1003
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: 2017 International and 2018 European guidelines are the most recent guidelines for intraductal papillary mucinous neoplasms management.AIM: to evaluate the diagnostic accuracy of these guidelines in identifying malignant IPMN.METHODS: data from resected patients with IPMN were collected in two referral centers. Features of risk associated to cancerous degeneration described in International and European guidelines were retrospectively applied. Sensitivity, specificity, positive and negative predictive value in detecting malignant disease were calculated.RESULTS: the study includes 627 resected patients. European guidelines suggest resection in any patient with at least one feature of moderate-risk. International guidelines suggest that patients with moderate-risk features undergo endoscopic ultrasound before surgery. European guidelines had a higher sensitivity (99.2% vs. 83%) but a lower positive predictive value (59.5% vs. 65.8%) and Specificity (2% vs. 37.5%). European guidelines detected almost all malignancies, but 40% of resected patients had low-grade dysplasia. 297 patients underwent endoscopic ultrasound before surgery. 31/116 (26.7%) tumors radiologically classified as "worrisome features" were reclassified as "high-risk stigmata" by endoscopic ultrasound and 24/31 were malignant IPMN.CONCLUSIONS: European and International guidelines have a relatively low diagnostic accuracy, being European guidelines more aggressive. Endoscopic ultrasound can improve guidelines accuracy in patients with moderate-risk features.
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7.
  • Franklin, Oskar, 1985-, et al. (författare)
  • Adjuvant chemotherapy with or without radiotherapy for resected pancreatic cancer after multiagent neoadjuvant chemotherapy
  • 2024
  • Ingår i: Annals of Surgical Oncology. - : Springer Nature. - 1068-9265 .- 1534-4681. ; 31:8, s. 4966-4975
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting.Methods: This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45–50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup.Results: Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61–0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37–0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44–0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors.Conclusion: After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors.
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8.
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10.
  • Franklin, Oskar, 1985- (författare)
  • Stromal components and micro-RNAs as biomarkers in pancreatic cancer
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background Pancreatic ductal adenocarcinoma (PDAC) patients have the poorest 5-year survival rates of all cancer forms. It is difficult to diagnose at early disease stages, tumour relapse after surgery is common, and current chemotherapies are ineffective. Carbohydrate antigen 19-9 (Ca 19-9), the only clinically implemented PDAC biomarker, is insufficient for diagnostic and screening purposes.PDAC tumours are characterised by a voluminous stroma that is rich in extracellular matrix (ECM) molecules such as collagens, hyaluronan (HA) and matricellular proteins. These stromal components have been suggested to promote PDAC cell migration, proliferation, evasion of apoptosis and chemotherapy resistance. Those events are mediated via interactions with adhesion receptors, such as integrins and CD44 receptors expressed on cancer cell surfaces.Micro-RNAs (miRNA) post-transcriptionally regulate gene expression in health and disease. At the time of PDAC diagnosis, miRNA levels are altered both in plasma and tumour tissue. Before PDAC diagnosis, tissue miRNA levels are altered in precursor lesions, raising the possibility that plasma miRNAs might aid in early detection.In this thesis, it is hypothesised that stromal components and miRNAs can serve as tissue or blood based biomarkers in PDAC. The aims are: (1) to characterise the expression of stromal components and their receptors in normal and cancerous tissue; (2) to find potential stroma-associated tissue and blood-based biomarkers for diagnosis and prognosis estimates; (3) to determine the cellular effects of type IV collagen (Col IV) in PDAC; (4) to determine if plasma miRNAs that are altered in manifest PDAC can be used to diagnose PDAC earlier.Methods The expression patterns of Col IV, Col IV-binding integrin subunits (α1, α2, β1), Endostatin, Osteopontin (OPN) and Tenascin C (TNC) were analysed in frozen PDAC and normal pancreatic tissue. A tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded primary tumours and lymph node metastases. The TMA was used to study the expression levels and associations with survival of the standard CD44 receptor (CD44s), its variant isoform 6 (CD44v6), HA, OPN and Col IV. Circulating levels of HA, Col IV, Endostatin, OPN and TNC were measured in PDAC patients and healthy individuals, and compared with conventional tumour markers (Ca 19-9, CEA, Ca 125 and TPS). The functional roles of Col IV were studied in PDAC cell lines by: (1) growth on different matrices (2) blocking Col IV binding integrin subunits, (3) blocking the Col IV domains 7s, CB3 and NC1, and (4) by down regulation of PDAC cell synthesis of Col IV using siRNA transfection. Plasma miRNAs alterations were screened for in samples from patients with manifest disease, using real-time quantitative PCR (RT-qPCR). To find early miRNA alterations, levels of those miRNAs that were altered at diagnosis were measured in prediagnostic plasma samples.Results High tissue expression of both the standard CD44 receptor (CD44s) and its variant isoform CD44v6 as well as low expression of stromal OPN were associated with poor survival. In addition, high CD44s and low OPN predicted poor survival independent of established prognostic factors.Circulating Col IV, Endostatin, OPN, TNC and HA were increased in preoperative samples from PDAC patients. Preoperatively, higher levels of serum-HA and plasma-Endostatin were associated with shorter survival. Postoperatively, higher levels of Col IV, Endostatin and OPN were associated with shorter survival. On the contrary, only one of the conventional tumour markers was associated with survival (Ca 125).Col IV stimulated PDAC cell proliferation and migration and inhibited apoptosis in vitro, dependent on the collagenous domain (CB3) of Col IV and the Col IV binding integrin subunit β1. Reduced endogenous Col IV synthesis inhibited these effects, suggesting that PDAC cells synthesise Col IV to stimulate tumour-promoting events via a newly discovered autocrine loop.15 miRNAs were altered in early stage PDAC patients and the combination of these markers outperformed Ca 19-9 in discriminating patients from healthy individuals. However, none of the miRNAs were altered in prediagnostic samples, suggesting that plasma miRNA alterations appear late in the disease course.Conclusions Up regulated stromal components in PDAC tumours are detectable in blood samples and are potential diagnostic and prognostic biomarkers in PDAC. High circulating levels of Col IV, Endostatin, OPN and HA predict poor survival, as well as high expression of CD44s and CD44v6 and low expression of OPN in tumour tissue. PDAC cells synthesise Col IV, which forms BM-like structures close to cancer cells and promote tumour progression in vitro via an autocrine loop. Several plasma-miRNAs are altered in PDAC, but are not useful for early discovery. 
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11.
  • Fusai, Giuseppe Kito, et al. (författare)
  • Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries
  • 2023
  • Ingår i: British Journal of Surgery. - : OXFORD UNIV PRESS. - 0007-1323 .- 1365-2168.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries. Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761).
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12.
  • Halimi, Asif, et al. (författare)
  • Isolation of pancreatic microbiota from cystic precursors of pancreatic cancer with intracellular growth and DNA damaging properties
  • 2021
  • Ingår i: Gut microbes. - : Taylor & Francis Group. - 1949-0976 .- 1949-0984. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Emerging research suggests gut microbiome may play a role in pancreatic cancer initiation and progression, but cultivation of the cancer microbiome remains challenging. This pilot study aims to investigate the possibility to cultivate pancreatic microbiome from pancreatic cystic lesions associated with invasive cancer. Intra-operatively acquired pancreatic cyst fluid samples showed culture-positivity mainly in the intraductal papillary mucinous neoplasm (IPMN) group of lesions. MALDI-TOF MS profiling analysis shows Gammaproteobacteria and Bacilli dominate among individual bacteria isolates. Among cultivated bacteria, Gammaproteobacteria, particularly Klebsiella pneumoniae, but also Granulicatella adiacens and Enterococcus faecalis, demonstrate consistent pathogenic properties in pancreatic cell lines tested in ex vivo co-culture models. Pathogenic properties include intracellular survival capability, cell death induction, or causing DNA double-strand breaks in the surviving cells resembling genotoxic effects. This study provides new insights into the role of the pancreatic microbiota in the intriguing link between pancreatic cystic lesions and cancer.
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13.
  • Hashimoto, Daisuke, et al. (författare)
  • Is surgical resection justified for pancreatic ductal adenocarcinoma with distant abdominal organ metastasis? A position paper by experts in pancreatic surgery at the Joint Meeting of the International Association of Pancreatology (IAP) & the Japan Pancreas Society (JPS) 2022 in Kyoto
  • 2023
  • Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 23:6, s. 682-688
  • Forskningsöversikt (refereegranskat)abstract
    • Pancreatic ductal adenocarcinoma (PDAC) is a typical refractory malignancy, and many patients have distant organ metastases at diagnosis, such as liver metastasis and peritoneal dissemination. The standard treatment for unresectable PDAC with distant organ metastasis (UR-M) is chemotherapy, but the prognosis remained poor. However, with recent dramatic developments in chemotherapy, the prognosis has gradually improved, and some patients have experienced marked shrinkage or disappearance of their metastatic lesions. With this trend, attempts have been made to resect a small number of metastases (so-called oligometastases) in combination with the primary tumor or to resect the primary and metastatic tumor in patients with a favorable response to anti-cancer treatment after a certain period of time (so-called conversion surgery). An international consensus meeting on surgical treatment for UR-M PDAC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of the Japan Pancreas Society (JPS) in Kyoto in July 2022. The presenters showed their indications for and results of surgical treatment for UR-M PDAC and discussed their advantages and disadvantages with the experts. Although these reports were limited to a small number of patients, findings suggest that these surgical treatments for patients with UR-M PDAC who have had a significant response to chemotherapy may contribute to a prognosis of prolonged survival. We hope that this article summarizing the discussion and agreements at the meeting will serve as the basis for future trials and guidelines.
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14.
  • Holmberg, Marcus, et al. (författare)
  • Outcome after resection for invasive intraductal papillary mucinous neoplasia is similar to conventional pancreatic ductal adenocarcinoma
  • 2021
  • Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 21:7, s. 1371-1377
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/objectives: Resections for intraductal papillary mucinous neoplasm (IPMN) have increased last decades. Overall survival (OS) for conventional pancreatic ductal adenocarcinoma (PDAC) is well known but OS for invasive IPMN (inv-IPMN) is not as conclusive. This study aims to elucidate potential differences in clinicopathology and OS between these tumor types and to investigate if the raised number of resections have affected outcome.Methods: Consecutive patients ≥18 years of age resected for inv-IPMN and PDAC at Karolinska University Hospital between 2009 and 2018 were included. Clinicopathological variables were analyzed in multivariable regression models. Outcome was assessed calculating two-year OS, estimating OS using the Kaplan-Meier model and comparing survival functions with log-rank test.Results: 513 patients were included, 122 with inv-IPMN and 391 with PDAC. During the study period both the proportion resected inv-IPMN and two-year OS, irrespective of tumor type, increased (2.5%–45%; p < 0.001 and 44%–57%; p = 0.005 respectively). In Kaplan-Meier survival analysis inv-IPMN had more favorable median OS (mOS) compared to PDAC (33.6 months vs 19.3 months, p = 0.001). However, in multivariable Cox Regression analysis, tumor type was not a predictor for death, but so were resection period, tumor subtype and N-stage (all p < 0.001).Conclusion: In this large single center observational cohort study, inv-IPMN seemed to have favorable survival outcome compared to PDAC, but after adjusting for predictors for death this benefit vanished. The combination of a pronounced increase in resected inv-IPMN and a concurrent hazard abatement for death within 2 years during the study period proved to be a principal factor.
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15.
  • Karam, Elias, et al. (författare)
  • Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia : A Multi-Institutional Pancreas2000/EPC Study
  • 2023
  • Ingår i: Neuroendocrinology. - 0028-3835. ; 113:10, s. 1024-1034
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. Methods: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. Results: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. Conclusion: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.
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16.
  • Karam, Elias, et al. (författare)
  • Outcomes of rescue procedures in the management of locally recurrent ampullary tumors : A Pancreas 2000/EPC study
  • 2023
  • Ingår i: Surgery (United States). - : Elsevier BV. - 0039-6060. ; 173:5, s. 1254-1262
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Ampullary lesions are rare and can be locally treated either with endoscopic papillectomy or transduodenal surgical ampullectomy. Management of local recurrence after a first-line treatment has been poorly studied. Methods: Patients with a local recurrence of an ampullary lesion initially treated with endoscopic papillectomy or transduodenal surgical ampullectomy were retrospectively included from a multi-institutional database (58 centers) between 2005 and 2018. Results: A total of 103 patients were included, 21 (20.4%) treated with redo endoscopic papillectomy, 14 (13.6%) with transduodenal surgical ampullectomy, and 68 (66%) with pancreaticoduodenectomy. Redo endoscopic papillectomy had low morbidity with 4.8% (n = 1) severe to fatal complications and a R0 rate of 81% (n = 17). Transduodenal surgical ampullectomy and pancreaticoduodenectomy after a first procedure had a higher morbidity with Clavien III and more complications, respectively, 28.6% (n = 4) and 25% (n = 17); R0 resection rates were 85.7% (n = 12) and 92.6% (n = 63), both without statistically significant difference compared to endoscopic papillectomy (P = .1 and 0.2). Pancreaticoduodenectomy had 4.4% (n = 2) mortality. No deaths were registered after transduodenal surgical ampullectomy or endoscopic papillectomy. Recurrences treated with pancreaticoduodenectomy were more likely to be adenocarcinomas (79.4%, n = 54 vs 21.4%, n = 3 for transduodenal surgical ampullectomy and 4.8%, n = 1 for endoscopic papillectomy, P < .0001). Three-year overall survival and disease-free survival were comparable. Conclusion: Endoscopy is appropriate for noninvasive recurrences, with resection rate and survival outcomes comparable to surgery. Surgery applies more to invasive recurrences, with transduodenal surgical ampullectomy rather for carcinoma in situ and early cancers and pancreaticoduodenectomy for more advanced tumors.
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17.
  • Kim, Hyeong Seok, et al. (författare)
  • Development, validation, and comparison of a nomogram based on radiologic findings for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas : An international multicenter study
  • 2021
  • Ingår i: Journal of hepato-biliary-pancreatic sciences. - : Wiley-Blackwell. - 1868-6974 .- 1868-6982.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms.METHODS: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct >10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients.RESULTS: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P = .014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P = .255).CONCLUSIONS: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.
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18.
  • Löhr, Johannes-Matthias, et al. (författare)
  • Outcome of probe-based confocal laser endomicroscopy (pCLE) during endoscopic retrograde cholangiopancreatography : a single-center prospective study in 45 patients.
  • 2015
  • Ingår i: United European Gastroenterology journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 3:6, s. 551-560
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Diagnosis of pre-malignant and malignant lesions in the bile duct and the pancreas is sometimes cumbersome. This applies in particular to intraductal papillary mucinous neoplasia (IPMN) and bile duct strictures in primary sclerosing cholangitis (PSC).AIMS: To evaluate in a prospective cohort study the sensitivity and specificity of probe-based confocal laser microscopy (pCLE) during endoscopic retrograde cholangiopancreatography (ERCP).METHODS: We performed pCLE together with mother-baby endoscopy (SpyGlass) during 50 ERCP sessions in 45 patients. The Miami and Paris criteria were applied. Clinical diagnosis via imaging was compared to pCLE and the final pathological diagnosis from surgically-resected, biopsy, or cytology specimens. Patients were followed up for at least 1 year.RESULTS: We were able to perform pCLE in all patients. Prior to endoscopy, the diagnosis was benign in 23 patients and undetermined (suspicious) in 16 patients, while six patients had an unequivocal diagnosis of malignancy. Sensitivity was 91% and specificity 52%. The positive (PPV) and negative predictive value (NPV) was 82% and 100%, respectively. Apart from mild post-ERCP pancreatitis in two patients, no complications occurred.CONCLUSIONS: Our study showed that pCLE is a safe, expert endoscopic method with high technical feasibility, high sensitivity and high NPV. It provided diagnostic information that can be helpful for decisions on patient management, especially in the case of IPMN and unclear pancreatic lesions, in individuals whom are at increased risk for pancreatic cancer.
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19.
  • Morgell, Ann, et al. (författare)
  • Metabolic Characterization of Plasma and Cyst Fluid from Cystic Precursors to Pancreatic Cancer Patients Reveal Metabolic Signatures of Bacterial Infection
  • 2021
  • Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 20:5, s. 2725-2738
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, with a 5 year survival rate as low as 9%. One factor complicating the management of pancreatic cancer is the lack of reliable tools for early diagnosis. While up to 50% of the adult population has been shown to develop precancerous pancreatic cysts, limited and insufficient approaches are currently available to determine whether a cyst is going to progress into pancreatic cancer. Recently, we used metabolomics approaches to identify candidate markers of disease progression in patients diagnosed with intraductal papillary mucinous neoplasms (IPMNs) undergoing pancreatic resection. Here, we enrolled an independent cohort to verify the candidate markers from our previous study with orthogonal quantitative methods in plasma and cyst fluid from serous cystic neoplasm and IPMN (either low- or high-grade dysplasia or pancreatic ductal adenocarcinoma). We thus validated these markers with absolute quantitative methods through the auxilium of stable isotope-labeled internal standards in a new independent cohort. Finally, we identified novel markers of IPMN status and disease progression - including amino acids, carboxylic acids, conjugated bile acids, free and carnitine-conjugated fatty acids, purine oxidation products, and trimethylamine-oxide. We show that the levels of these metabolites of potential bacterial origin correlated with the degree of bacterial enrichment in the cyst, as determined by 16S RNA. Overall, our findings are interesting per se, owing to the validation of previous markers and identification of novel small molecule signatures of IPMN and disease progression. In addition, our findings further fuel the provoking debate as to whether bacterial infections may represent an etiological contributor to the development and severity of the disease in pancreatic cancer, in like fashion to other cancers (e.g., Helicobacter pylori and gastric cancer).
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20.
  • Olsson, Greger, et al. (författare)
  • Preoperative biliary drainage by plastic or self-expandable metal stents in patients with periampullary tumors : results of a randomized clinical study.
  • 2017
  • Ingår i: Endoscopy international open. - : Georg Thieme Verlag KG. - 2364-3722 .- 2196-9736. ; 5:9, s. E798-E808
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND STUDY AIMS : Preoperative biliary drainage in patients with periampullary tumors and jaundice has been popularized to improve the quality of life and minimize the risks associated with subsequent radical surgery. The aim of this study was to investigate the possible superiority of self-expandable metal stents (SEMS) over plastic stents, by comparing the amount of bacteria in intraoperatively collected bile and using this variable as a proxy for the efficacy of the respective biliary drainage modalities.PATIENTS AND METHODS : In this randomized clinical trial, 92 patients with obstructive jaundice were enrolled; 45 were allocated to the plastic stent group and 47 to the SEMS group. The primary outcome was the extent and magnitude of biliary bacterial growth at the time of surgical exploration. Secondary outcomes were: macroscopic grading of inflammation of the stented bile ducts, occurrence of adverse events after stenting, stent dysfunction, recognized surgical complexities, and incidence of postoperative complications.RESULTS:  = 0.03). Postoperative complications in patients who underwent curative surgery were more common in patients with plastic stents (72 % vs. 52 %), among which clinically significant leakage from the pancreatic anastomoses seemed to predominate (12 % vs. 3.7 %); however, none of these differences in postoperative adverse events reached statistical significance.CONCLUSION:  This randomized clinical study was unable to demonstrate any superiority of SEMS in the efficacy of preoperative bile drainage, as assessed by the amount of bacteria in the intraoperatively collected bile. However, some data in favor of SEMS were observed among the clinical secondary outcomes variables (preoperative stent exchange rates) without increases in local inflammatory reactions.
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21.
  • Pozzi Mucelli, Raffaella M., et al. (författare)
  • Branch-duct intraductal papillary mucinous neoplasm (IPMN) : Are cyst volumetry and other novel imaging features able to improve malignancy prediction compared to well-established resection criteria?
  • 2022
  • Ingår i: European Radiology. - : Springer Science+Business Media B.V.. - 0938-7994 .- 1432-1084. ; 32:8, s. 5144-5155
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Current guidelines base the management of intraductal papillary mucinous neoplasms (IPMN) on several well-established resection criteria (RC), including cyst size. However, malignancy may occur in small cysts. Since branch-duct (BD) IPMN are not perfect spheres, volumetric and morphologic analysis might better correlate with mucin production and grade of dysplasia. Nonetheless, their role in malignancy (high-grade dysplasia/invasive cancer) prediction has been poorly investigated. Previous studies evaluating RC also included patients with solid-mass-forming pancreatic cancer (PC), which may affect the RC yield. This study aimed to assess the role of volume, morphology, and other well-established RC in malignancy prediction in patients with BD- and mixed-type IPMN after excluding solid masses.Methods: Retrospective ethical review-board-approved study of 106 patients (2008–2019) with histopathological diagnosis of BD- and mixed-type IPMN (without solid masses) and preoperative MRI available. Standard imaging and clinical features were collected, and the novel imaging features cyst-volume and elongation value [EV = 1 − (width/length)] calculated on T2-weighted images. Logistic regression analysis was performed. Statistical significance set at two-tails, p < 0.05.Results: Neither volume (odds ratio (OR) = 1.01, 95% CI: 0.99–1.02, p = 0.12) nor EV (OR = 0.38, 95% CI: 0.02–5.93, p = 0.49) was associated with malignancy. Contrast-enhancing mural nodules (MN), main pancreatic duct (MPD) ≥ 5 mm, and elevated carbohydrate antigen (CA) 19-9 serum levels (> 37 μmol/L) were associated with malignancy (MN OR: 4.32, 95% CI: 1.18–15.76, p = 0.02; MPD ≥ 5 mm OR: 4.2, 95% CI: 1.34–13.1, p = 0.01; CA19-9 OR: 6.72; 95% CI: 1.89 – 23.89, p = 0.003).Conclusions: Volume and elongation value cannot predict malignancy in BD- and/or mixed-type IPMN. Mural nodules, MPD ≥ 5 mm and elevated CA19-9 serum levels are associated with higher malignancy risk even after the exclusion of solid masses. Key Points: • Novel and well-established resection criteria for IPMN have been evaluated after excluding solid masses. • BD-IPMN volume and elongation value cannot predict malignancy. • Main pancreatic duct ≥ 5 mm, mural nodules, and elevated carbohydrate antigen 19-9 levels are associated with malignancy.
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22.
  • Reuterwall, Marcus, et al. (författare)
  • The clinical value of ERCP-guided cholangiopancreatoscopy using a single-operator system
  • 2019
  • Ingår i: BMC Gastroenterology. - : BioMed Central. - 1471-230X. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Single-operator, per-oral cholangiopancreatoscopy (SOPCP) enables direct biliopancreatic ductal visualization, targeted tissue sampling, and therapeutic intervention. At Karolinska University Hospital, SOPCP was introduced early and has since been extensively utilized according to a standardized protocol. We analysed the clinical value of SOPCP in the diagnosis and treatment of biliopancreatic diseases in a single high volume center.METHODS: All SOPCP procedures performed between March 2007 and December 2014 were retrospectively reviewed. Each procedure's diagnostic yield and therapeutic value was evaluated using a predefined 4 grade scale; 1 - no diagnostic or therapeutic value, 2 - information gained did not impact clinical decision-making and in case of a therapeutic intervention, did not alter the clinical course of the patient, 3 - information gained had an impact on clinical decision-making and in the case of a therapeutic intervention, assisted subsequent disease management, and finally, 4 - information gained was essential and critical for clinical decision-making and in case of a therapeutic intervention, solved the clinical problem requiring no further therapeutic actions. Descriptive statistics were used to analyse results, with uni- and multivariate analyses completed to assess risk of adverse events.RESULTS: During the study period, 365 SOPCP procedures were performed. We found SOPCP of pivotal importance (grade 4) in 19% of cases, and of great clinical significance (grade 3) in 44% of cases. SOPCP did not affect clinical decision-making or alter clinical course (grade 1 and 2) in 37% of cases.CONCLUSION: SOPCP offers direct access to the biliopancreatic ducts for both diagnostic and therapeutic purposes, adding significant clinical value in 64% of cases.TRIAL REGISTRATION: As this is a purely observational and retrospectively registered study in which the assignment of the medical intervention was not at the discretion of the investigator, it has not been registered in a registry.
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23.
  • Sanjeevi, Srinivas, et al. (författare)
  • Comparison of end-to-end invagination and duct-to-mucosa pancreaticojejunostomies following Whipple's resection : A randomized controlled trial in patients at high risk of postoperative pancreatic fistula
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Postoperative pancreatic fistula (POPF) is a major cause of morbidity and mortality after pancreatic resection. Various pancreatoenteric reconstruction techniques exist, yet there is no consensus on the optimal strategy to decrease POPF. The aim of this trial was to compare a novel end-to-end invaginated pancreaticojejunostomy (INV) with the duct-to-mucosa anastomosis (DM) in patients at high risk for POPF. Methods: Consecutive patients between September 2011 and 2015 that were evaluated at a multidisciplinary tumor board and planned for a pancreaticoduodenectomy were randomized prospectively to INV or DM, in an unblinded dual-institution superiority trial. All patients had an assessment of their pancreatic gland both pre- and intra-operatively to select for patients at high risk for POPF. The primary end point was clinically relevant POPF as classified by established definitions.  Secondary outcomes were postoperative mortality and morbidity.Results: Hundred and twenty-three patients were included in the final analysis (61 DM, 62 INV). All patients had a soft pancreas with a main pancreatic duct <3mm. There was no difference in clinically significant pancreatic leaks (POPF B-C) between the groups (p=0.72). Significantly fewer cases of POPF C were observed in the INV group compared to the DM group (DM n=13, INV n=2, p=0.002). Six life-threatening complications (Clavien-Dindo IV) occurred in the DM group, compared to one in the INV group (p=0.06). Grade C post-pancreatectomy hemorrhage was significantly higher in the DM group (DM n=7, INV n=0, p=0.006). There were no differences between the groups in median operating times, in-hospital mortality, or blood loss. Conclusion: The end-to-end invagination pancreaticojejunostomy is not significantly superior with regards to clinically significant POPF. It does however appear to be a safe reconstruction technique, possibly associated with a lower incidence of severe POPF and post-pancreatectomy hemorrhage. 
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24.
  • Stoop, Thomas F., et al. (författare)
  • Pathological complete response in patients with resected pancreatic adenocarcinoma after preoperative chemotherapy
  • 2024
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection.Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
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25.
  • Stoop, Thomas F., et al. (författare)
  • Surgical Outcomes After Total Pancreatectomy : A High-Volume Center Experience
  • 2021
  • Ingår i: Annals of Surgical Oncology. - : Springer. - 1068-9265 .- 1534-4681. ; 28:3, s. 1543-1551
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The impact of high-volume care in total pancreatectomy (TP) is barely explored since annual numbers are mostly low. This study evaluated surgical outcomes after TP over time in a high-volume center.Methods: All adult patients (age >= 18 years) who underwent an elective single-stage TP at Karolinska University Hospital were retrospectively analysed (2008-2017). High volume was defined as > 20 TPs/year.Results: Overall, 145 patients after TP were included, including 86 (59.3%) extended resections. Major morbidity was 34.5% (50/145) and 90-day mortality 5.5% (8/145). The relative use of TP within all pancreatectomies increased from 5.4% (63/1175) in 2008-2015 to 17.3% (82/473) in 2016-2017 (p < 0.001). Over time, TP was more often performed to achieve radicality (n = 11, 17.5% ton = 31, 37.8%;p = 0.007). In multivariable logistic regression analysis, an annual TP-volume of > 20 was associated with reduced major morbidity (odds ratio [OR] = 0.225, 95% confidence interval [CI], 0.097-0.521;p < 0.001). In the high-volume years (2016-2017), major morbidity (n = 31, 49.2% ton = 19, 23.2%;p = 0.001) and relaparotomy rate (n = 13, 20.6% ton = 5, 6.1%;p = 0.009) improved. Improvements occurred mainly after extended TP, including lower major morbidity (n = 22, 57.9% ton = 12, 25.0%;p = 0.002) and in-hospital mortality (n = 3, 7.9% ton = 0, 0%;p = 0.082).Conclusions: In a single, high-volume center study, an increase in surgical volume of TP was associated with improved perioperative outcomes, especially for extended resections.
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