Pancreatic medullary carcinoma developed on a pancreatic intraductal papillary mucinous neoplasm with loss of MSH2 and MSH6 expression: a case report

Abstract Background Pancreatic medullary carcinoma (PMC) is a rare pancreatic tumor, usually showing the presence of microsatellite instability, mostly MLH1 silencing, and a wild-type KRAS mutation status. We report here a PMC arising from a Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN), both having KRAS and TP53 mutations. Case presentation We report the case of a 73-year-old woman presenting with right iliac fossa pain. MRI revealed a 16 mm diameter mass in the pancreas, leading to a pancreatic duct stricture and upstream a dilatation of the distal pancreatic duct of Wirsung. A fine needle aspiration was performed, and pathology analysis revealed malignant glandular cells. The patient underwent distal pancreatectomy. Gross examination revealed an12 mm indurated white lesion, adjacent to a cystic lesion extending into the rest of the pancreatic body. Microscopically, the cystic area represented a mixed (gastric-type and pancreatobiliary-type) IPMN, involving the main and secondary pancreatic ducts with low-grade and high-grade dysplasia. In the periphery of this IPMN, a 14mm associated invasive carcinoma was observed, characterized by focal gland formation and by poorly differentiated cells with a syncytial appearance, associated with a dense lymphoplasmocytic and neutrophilic infiltrate. Immunohistochemical analyses showed loss of MSH2 and MSH6 expression. Microsatellite instability was confirmed by molecular test. Molecular analysis was performed both on the invasive carcinoma and on the high-grade dysplasia IPMN, revealing the same mutation profile with KRAS and TP53 mutations. The proposed diagnosis was mixed IPMN with associated invasive medullary carcinoma that presented loss of MSH2 and MSH6 expression. Conclusions The present case reports for the first time, at the best of our knowledge, the coexistence of IPMN lesions and PMC, both having the same molecular alterations. It also describes the second case of PMC with microsatellite instability, MSH2 and MSH6 silenced.info:eu-repo/semantics/publishe

Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants

Hydroxychloroquine (HCQ) has been largely used and investigated as therapy for COVID-19 across various settings at a total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use of low-dose HCQ (total 2400 mg over 5 days) was recommended for hospitalised patients with COVID-19. We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19 hospital surveillance data. Patients treated either with HCQ monotherapy and supportive care (HCQ group) were compared with patients treated with supportive care only (no-HCQ group) using a competing risks proportional hazards regression with discharge alive as competing risk, adjusted for demographic and clinical features with robust standard errors. Of 8075 patients with complete discharge data on 24 May 2020 and diagnosed before 1 May 2020, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the multivariable analysis, mortality was lower in the HCQ group compared with the no-HCQ group [adjusted hazard ratio (aHR) = 0.684, 95% confidence interval (CI) 0.617-0.758]. Compared with the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤5 days (n = 3975) and >5 days (n = 3487) after symptom onset [aHR = 0.701 (95% CI 0.617-0.796) and aHR = 0.647 (95% CI 0.525-0.797), respectively]. Compared with supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalised patients with COVID-19 diagnosed and treated early or later after symptom onset.status: publishe

Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants

Hydroxychloroquine (HCQ) has been largely used and investigated as therapy for COVID-19 across&nbsp;various settings at a total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use&nbsp;of low-dose HCQ (total 2400 mg over 5 days) was recommended for hospitalised patients with COVID-19. We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19&nbsp;hospital surveillance data. Patients treated either with HCQ monotherapy and supportive care (HCQ group)&nbsp;were compared with patients treated with supportive care only (no-HCQ group) using a competing risks&nbsp;proportional hazards regression with discharge alive as competing risk, adjusted for demographic and&nbsp;clinical features with robust standard errors. Of 8075 patients with complete discharge data on 24 May&nbsp;2020 and diagnosed before 1 May 2020, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the&nbsp;multivariable analysis, mortality was lower in the HCQ group compared with the no-HCQ group [adjusted hazard&nbsp;ratio (aHR) = 0.684, 95% confidence interval (CI) 0.617–0.758]. Compared with the no-HCQ group,&nbsp;mortality in the HCQ group was reduced both in patients diagnosed ≤5 days ( n = 3975) and &gt; 5 days ( n =&nbsp;3487) after symptom onset [aHR = 0.701 (95% CI 0.617–0.796) and aHR = 0.647 (95% CI 0.525–0.797),&nbsp;respectively]. Compared with supportive care only, low-dose HCQ monotherapy was independently&nbsp;associated with lower mortality in hospitalised patients with COVID-19 diagnosed and treated early or later&nbsp;after symptom&nbsp;onset.</p

Impact of solid cancer on in-hospital mortality overall and among different subgroups of patients with COVID-19: a nationwide, population-based analysis

info:eu-repo/semantics/publishe

Nationwide Harmonization Effort for Semi-Quantitative Reporting of SARS-CoV-2 PCR Test Results in Belgium.

From early 2020, a high demand for SARS-CoV-2 tests was driven by several testing indications, including asymptomatic cases, resulting in the massive roll-out of PCR assays to combat the pandemic. Considering the dynamic of viral shedding during the course of infection, the demand to report cycle threshold (Ct) values rapidly emerged. As Ct values can be affected by a number of factors, we considered that harmonization of semi-quantitative PCR results across laboratories would avoid potential divergent interpretations, particularly in the absence of clinical or serological information. A proposal to harmonize reporting of test results was drafted by the National Reference Centre (NRC) UZ/KU Leuven, distinguishing four categories of positivity based on RNA copies/mL. Pre-quantified control material was shipped to 124 laboratories with instructions to setup a standard curve to define thresholds per assay. For each assay, the mean Ct value and corresponding standard deviation was calculated per target gene, for the three concentrations (10, 10 and 10 copies/mL) that determine the classification. The results of 17 assays are summarized. This harmonization effort allowed to ensure that all Belgian laboratories would report positive PCR results in the same semi-quantitative manner to clinicians and to the national database which feeds contact tracing interventions