Does the surgical waiting list affect pathological and survival outcome in resectable pancreatic ductal adenocarcinoma?

Marchegiani, Giovanni; Andrianello, Stefano; Perri, Giampaolo; Secchettin, Erica; Maggino, Laura; Malleo, Giuseppe; Bassi, Claudio

doi:10.1016/j.hpb.2017.10.017

Cited by 28 publications

(29 citation statements)

References 26 publications

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“…Notably, TSPAN8 serves as a prognostic marker in other cancer types as well 37 . Apart from time between surgery and chemotherapy, time to surgery may play an important role in PDAC as well (waiting for more than 30 days for surgery after diagnosis has been associated to an increase in tumor size) 43 . DEG DKK4 (also top 1% DADA gene) is the least studied protein from the Dickkopf (DKK) family, which includes DKK3 44 and DKK1 44 .…”

Section: Discussionmentioning

confidence: 99%

Deeper insights into long-term survival heterogeneity of Pancreatic Ductal Adenocarcinoma (PDAC) patients using integrative individual- and group-level transcriptome network analyses

Bhardwaj

Josse

Daele

et al. 2020

Preprint

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Background: Pancreatic ductal adenocarcinoma (PDAC) is categorized as the seventh leading cause of cancer mortality worldwide. Its predictive markers for long-term survival are not well known. Therefore, it is interesting to delineate individual-specific perturbed genes when comparing long-term (LT) and short-term (ST) PDAC survivors, and to exploit the integrative individual-and group-based transcriptome profiling.Method: Using a discovery cohort of 19 PDAC patients from CHU-Liège (Belgium), we first performed differential gene expression (DGE) analysis comparing LT to ST survivor. Second, we adopted unsupervised systems biology approaches to obtain gene modules linked to clinical features. Third, we created individual-specific perturbation profiles and identified key regulators across the LT patients. Furthermore, we applied two gene prioritization approaches: random walk-based Degree-Aware disease gene prioritizing (DADA) method to develop PDAC disease modules; Network-based Integration of Multi-omics Data (NetICS) to integrate group-based and individual-specific perturbed genes in relation to PDAC LT survival. Findings: We identified 173 differentially expressed genes (DEGs) in ST and LT survivors and five modules (including 38 DEGs) showing associations to clinical traits such as tumor size and chemotherapy. DGE analysis identified differences in genes involved in metabolic and cell cycle activity. Validation of DEGs in the molecular lab suggested a role of REG4 and TSPAN8 in PDAC survival. Individual-specific omics changes across LT survivors revealed biological signatures such as focal adhesion and extracellular matrix receptors, implying a potential role in molecular-level heterogeneity of LT PDAC survivors. Via NetICS and DADA we not only identified various known oncogenes such as CUL1, SCF62, EGF, FOSL1, MMP9, and TGFB1, but also highlighted novel genes (TAC1, KCNH7, IRS4, DKK4). Interpretation: Our proposed analytic workflow shows the advantages of combining clinical and omics data as well as individual-and group-level transcriptome profiling. It suggested novel potential transcriptome marks of LT survival heterogeneity in PDAC. Funding: Télévie-FRS-FNRS

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Section: Discussionmentioning

confidence: 99%

Deeper insights into long-term survival heterogeneity of Pancreatic Ductal Adenocarcinoma (PDAC) patients using integrative individual- and group-level transcriptome network analyses

Bhardwaj

Josse

Daele

et al. 2020

Preprint

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“…The start of this pathway was the date of initial CT, which is considered the single best investigation required for diagnosing, or at least raising suspicion of, periampullary cancer; this has been used elsewhere when reviewing outcomes of patients treated within these pathways. The sensitivity and specificity of CT in identifying pancreatic cancer is 70–100 per cent, and its ability to evaluate resectability based on locoregional, distant and vascular involvement is 81–99 per cent.…”

Section: Discussionmentioning

confidence: 99%

“…In the absence of a coordinated pathway, the need for multiple and/or specialist investigations, as well as multidisciplinary reviews, inevitably prolongs the time from presentation to surgery. Preoperative interventions to correct malnutrition and jaundice, both common problems in patients with periampullary cancer, may also serve to complicate the pathway further. Despite evidence that preoperative biliary drainage is harmful, patients with potentially resectable disease frequently undergo ERCP before referral to a specialist centre.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the clinical and economic impact of delays to surgery in patients with periampullary cancer

et al. 2019

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Background Early treatment is the only potential cure for periampullary cancer. The pathway to surgery is complex and involves multiple procedures across local and specialist hospitals. The aim of this study was to analyse variability within this pathway, and its impact on cost and outcomes. Methods Patients undergoing surgery for periampullary cancer (2011–2016) were identified retrospectively and their pathway to surgery was analysed. Patients who had early surgery (shortest quartile, Q1) were compared with those having late surgery (longest quartile, Q4). Results A total of 483 patients were included in the study, with 121 and 124 patients in Q1 and Q4 respectively. The median time from initial CT to surgery was 21 days for Q1 versus 112 days for Q4 (P < 0·001). Diagnostic delays were common in Q4; these patients required significantly more investigations than those in Q1 (endoscopic ultrasonography (EUS): 74·2 versus 18·2 per cent respectively, P < 0·001; MRI: 33·6 versus 20·6 per cent, P = 0·036). The median time to diagnostic EUS was 13 days in Q1 versus 59 days in Q4 (P < 0·001). Some 42·1 per cent of jaundiced patients in Q1 underwent preoperative biliary drainage, compared with all patients in Q4. There were significantly more unplanned admissions and associated longer duration of hospital stay per patient and costs in Q4 than in Q1 (median: 8 versus 3 days respectively; €5652 versus €2088; both P < 0·001). There was a higher likelihood of potentially curative surgery in Q1 (82·6 per cent versus 66·9 per cent in Q4; P = 0·005). Conclusion There is wide variation across the entire pathway, suggesting that multiple strategies are required to enable early surgery. Defining an effective pathway by anticipating the need for investigations and avoiding biliary drainage reduces unplanned admissions and costs and increases resection rates.

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“…Interim chemotherapy was an option in case of patients at a high risk of developing postoperative complications. Patients with cephalic lesions deserving a pancreatoduodenectomy were scheduled for surgery only in case of tumours smaller than 2 cm [77]. This subjects (for low comorbidities burden, optimal nutritional status and younger age) are the more likely to bene t from a radical resection and are at lower risk of developing postoperative complications, taking in consideration the availability of beds in the intensive care units for the COVID-19 pandemic.…”

Section: Guidelines/recommendation For Pancreatic Cancermentioning

confidence: 99%

The Clinical and Translational Research Activities at the INT – IRCCS “Fondazione Pascale” Center (Naples, Italy) during the COVID-19 Pandemic

Buonaguro¹,

Botti

Ascierto

et al. 2020

Preprint

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COVID-19 pandemic following the outbreak in China and Western Europe, where it finally lost the momentum, is now devastating North and South America. It has not been identified the reason and the molecular mechanisms of the two different patterns of the pulmonary host responses to virus from a minimal disease in young subjects to a severe distress syndrome (ARDS) in older subjects, particularly those with previous chronic diseases (including diabetes) and Cancer. The Management of the Istituto Nazionale Tumori - IRCCS “Fondazione Pascale” in Naples [INT-Pascale], along with all Health professionals decided not to interrupt the treatment of those hospitalized and to continue, even if after a careful triage in order not to allow SARS-CoV-2 positive subjects to access, to take care of cancer patients with serious conditions. Although very few (n=3) patients developed a symptomatic COVID-19 and required the transfer to a COVID-19 area of the Institute, no patients died during the Hospitalization and completed their oncology treatment. Besides monitoring of the patients, all employees of the Institute (physicians, nurses, researchers, lawyers, accountants, gatekeepers, guardians, janitors) have been tested for a possible exposure. Personnel identified as positive, has been promptly subjected to home quarantine and subdued to health surveillance. One severe case of respiratory distress has been reported in a positive employees and one death of a family member. Further steps to home monitoring of COVID-19 clinical course have been taken with the development of remote Wi-Fi connected digital devices for the detection of early signs of respiratory distress, including heart rate and oxygen saturation. In conclusion cancer care has been performed and continued safely also during COVID-19 pandemic and further remote home strategies are in progress to ensure the appropriate monitoring of cancer patients.

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Does the surgical waiting list affect pathological and survival outcome in resectable pancreatic ductal adenocarcinoma?

Abstract: The duration of the surgical waiting-list did not affect pathological features and survival. Delayed surgery was associated with increased cancer size on the specimen. However, surgery should not be delayed for PDACs < 20 mm as this may negatively affect the prognosis.

Cited by 28 publications

References 26 publications

Deeper insights into long-term survival heterogeneity of Pancreatic Ductal Adenocarcinoma (PDAC) patients using integrative individual- and group-level transcriptome network analyses

Deeper insights into long-term survival heterogeneity of Pancreatic Ductal Adenocarcinoma (PDAC) patients using integrative individual- and group-level transcriptome network analyses

Evaluation of the clinical and economic impact of delays to surgery in patients with periampullary cancer

The Clinical and Translational Research Activities at the INT – IRCCS “Fondazione Pascale” Center (Naples, Italy) during the COVID-19 Pandemic

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