4505 Background: Patients with borderline resectable pancreatic cancer have poor survival and low resection rates. Neoadjuvant therapy may improve the outcome for these patients. The aim of this trial was to determine the feasibility and efficacy of a comparison of immediate surgery versus neoadjuvant GEMCAP or FOLFIRINOX or CRT. Methods: Eligible patients with NCCN defined borderline resectable (following central review of the baseline CT scan) and biopsy proven pancreatic cancer were randomised (stratified by centre) to receive immediate surgery, or neoadjuvant therapy of either 2 cycles of GEMCAP, or 4 cycles of FOLFIRINOX or 50.4Gy capecitabine-based CRT in 28 daily fractions over 5 ½ weeks. Patients were restaged at 4-6 weeks and underwent surgical exploration if still borderline resectable. Resected patients received adjuvant therapy. Follow up was 12 months. There was quality assurance of surgery and CRT. Primary endpoints were recruitment rate and resection rate (R1/R0). Secondary endpoints included overall survival and toxicity. A target of 90 patients was set to determine feasibility and resection rates. Rates will be presented as point estimates and survival compared across treatment arms using a log-rank test. Analyses will be on an ITT basis. Results: Between August 2014 and December 2018, 90 patients were randomised with 88 included in the full analysis set (32 immediate surgery, 20 GEMCAP, 20 FOLFIRINOX, 16 CRT). Median age was 63 years, 44% were men. WHO performance status was 0 and 1 in 45% and 55% respectively. Median CA19-9 was 603 kU/L at baseline. 44 (79%) patients completed neoadjuvant therapy. Recruitment rate was 21 patients per year. Resection rate was 62% for immediate surgery and 55% for neoadjuvant therapy (p=0.668). R0 resection rate on resected patients was 15% and 23% respectively (p=0.721). One year survival rate was 40% [95% CI, 26% – 62%] for immediate surgery and 77% [95%CI, 66% - 89%] for neoadjuvant therapy. Log-rank analysis showed an HR=0.27 [95% CI, 0.13 – 0.55]; χ2 (1) = 14.91, P<0.001. 9 out of the 51 neoadjuvant patients included in the safety set reported 12 serious adverse events of grade 3 or above. Conclusions: There was no difference in resection rate between arms, however neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Clinical trial information: 89500674 .
ObjectiveThere is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection.DesignA prospective international multicentre cohort study including consecutive patients admitted with AP during the current pandemic was undertaken. Primary outcome measure was severity of AP. Secondary outcome measures were aetiology of AP, intensive care unit (ICU) admission, length of hospital stay, local complications, acute respiratory distress syndrome (ARDS), persistent organ failure and 30-day mortality. Multilevel logistic regression was used to compare the two groups.Results1777 patients with AP were included during the study period from 1 March to 23 July 2020. 149 patients (8.3%) had concomitant SARS-CoV-2 infection. Overall, SARS-CoV-2-positive patients were older male patients and more likely to develop severe AP and ARDS (p<0.001). Unadjusted analysis showed that SARS-CoV-2-positive patients with AP were more likely to require ICU admission (OR 5.21, p<0.001), local complications (OR 2.91, p<0.001), persistent organ failure (OR 7.32, p<0.001), prolonged hospital stay (OR 1.89, p<0.001) and a higher 30-day mortality (OR 6.56, p<0.001). Adjusted analysis showed length of stay (OR 1.32, p<0.001), persistent organ failure (OR 2.77, p<0.003) and 30-day mortality (OR 2.41, p<0.04) were significantly higher in SARS-CoV-2 co-infection.ConclusionPatients with AP and coexistent SARS-CoV-2 infection are at increased risk of severe AP, worse clinical outcomes, prolonged length of hospital stay and high 30-day mortality.
A s the global pandemic of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) continues, nuances of the disease it precipitates in humans continue to emerge. After early reports of presentation with gastrointestinal-type symptoms in China 1 and Italy, 2 a group from Wuhan reported a series of 9 patients with purported pancreatic injury in the context of SARS-CoV2 infection 3 but did not provide robust evidence for pancreatitis. relying on mild hyperamylasemia alone. Current international consensus for a diagnosis of acute pancreatitis requires 2 of the following 3 features: abdominal pain consistent with pancreatitis, serum amylase/lipase greater than 3 times the upper limit of normal, and characteristic findings on cross-sectional imaging. 4 Simply put, there are too many causes for hyperamylasemia in the context of systemic illness, with or without SARS-CoV2, for its use in isolation as a marker of pancreatic injury. Nonetheless, we report here 5 cases of atypical but proven acute pancreatitis in the context of SARS-CoV2 infection. Methods This review was registered with the Liverpool University Hospitals NHS Foundation Trust audit department (ID TA0002744). Cases were identified by searching admission diagnoses (International Classification of Diseases, 10th revision code K85) or radiology requests and reports for "acute pancreatitis." SARS-CoV2 was diagnosed when either swabs were positive on rapid polymerase chain reaction (VIASURE, Certest Biotec, Spain) or patients had radiologic evidence of SARS-CoV2 infection (Supplementary Figure 1). Cases with pre-existing pancreatic pathology or where the etiology was clearly non-SARS-CoV2 related were excluded. Data extracted from patient and radiology records were used to calculate clinical scores and hepatic steatosis estimates by analysis of contrast-enhanced computed tomography (CECT) images as previously described. 5 Imaging findings were rereported by an expert pancreatic radiologist.
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