Lurbinectedin in Refractory Diffuse Malignant Peritoneal Mesothelioma: Report of Two Cases.

Mesothelioma is a malignancy of serosal membranes. Parietal pleura is the most common site, with peritoneum being the second most frequent location. Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. The prognosis is often very poor with median overall survival ranging from 6 to 18 months in patients who are not candidates for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) due to non-resectable disease or comorbid conditions. For patients with resectable disease, CRS and HIPEC have become the standard of care. However, for patients with unresectable malignant mesothelioma there is unfortunately no effective systemic treatment beyond the first line. Based on the results of a recent phase II trial, lurbinectedin has clinical activity and acceptable toxicity in the second- and third-line treatment of malignant pleural mesothelioma. However, until present, no data have been available for patients with MPM and for patients who become refractory after multiple treatment lines. We report on two patients with metastatic MPM who achieved durable disease control of 10+ and 8 months with lurbinectedin in the fourth and fifth treatment line, respectively

Case Report: Vasculitis Triggered by SIRT in a Patient With Previously Untreated Cholangiocarcinoma.

Arising from the biliary tract, cholangiocarcinoma is a rare and aggressive epithelial cancer. According to the primary site, it can be further classified into intrahepatic, perihilar and distal types. Due to the lack of symptoms early in the disease course, most patients are diagnosed at advanced stages. Being not candidates for curative surgical management, these patients are treated with palliative systemic chemotherapy, and their prognosis remains poor. Using radioisotopes like yttrium-90 -labeled microspheres ( <sup>90</sup> Y), radioembolization represents a local approach to treat primary and secondary liver tumors. In the case of intrahepatic cholangiocarcinoma, radioembolization can be used as a primary treatment, as an adjunct to chemotherapy or after failing chemotherapy. An 88-year-old man underwent radioembolization for a previously untreated stage II intrahepatic cholangiocarcinoma. One week later, he presented to our clinic with a non-pruritic maculopapular rash of the lower extremities and abdomen, worsening fatigue and low-grade fever. Laboratory exams, including hepatitis screening, were within normal limits. Showing positive immunofluorescence staining for immunoglobulin M (IgM) and complement 3 (C3) in vessel walls without IgA involvement, the skin biopsy results were compatible with leukocytoclastic vasculitis. Apart from the anticancer intervention, there have been no recent medication changes which could explain this complication. Notably, we did not observe any side effects during or after the perfusion scan with technetium-99m macroaggregated albumin (MAA) performed prior to radioembolization. The symptoms resolved quickly after a short course of colchicine and did not reappear at cholangiocarcinoma progression. In the absence of other evident causes, we conclude that the onset of leukocytoclastic vasculitis in our patient was directly linked to the administration of yttrium-90 -labeled microspheres. Our report therefore demonstrates that this condition can be a rare but manageable complication of <sup>90</sup> Y liver radioembolization

Fatigue and functional capacity post COVID-19

Background: We explored if fatigue influenced the long-term functional capacity of patients post COVID-19. Methods: People after COVID -19, grouped by treatment setting (home - H, hospital ward - HW or intensive care unit – ICU), were studied 12 months after discharge. Fatigue-Functional Chronic Illness Assessment Questionnaire Fatigue Subscale, FACIT-F and functional capacity-6min walk test, 6MWD and 1min sit-to-stand test, 1minSTS were assessed. Groups were compared with one-way ANOVA or Kruskal-Wallis H test. Spearman’s ρ and multiple regression analyses were performed between fatigue-functional tests. Results: 148 subjects (H, n=44; HW, n=60; ICU, n=44) participated. Fatigue was clinically relevant at 12 months although not significantly different among groups [H: 41(35-49); HW: 42(33-50); ICU; 42(32-48) points; p=.979). Functional capacity was significantly higher in those treated at home (6MWD: H,626 114m, HW: 527 146m, ICU: 528 129m, p<.001; 1minSTS: H,29 11reps, HW: 23 8reps, ICU: 24 8reps, p<.002). Fatigue was significantly correlated with functional tests within each group (FACIT-F-6MWD,.317<ρ≤.550, p<.01; FACIT-F-1minSTS, .364<ρ≤.485, p<.01). Each point of FACIT-F could change 6MWD by 5-6m and 1minSTS by. 3-.5reps, explaining between 12-33% of change in 6MWD and 17-22% of change in 1minSTS (Table 1). Conclusions: Fatigue seems to influence functional capacity of patients post COVID-19. Early management of this symptom seems important for their long-term management.publishe

Gallbladder cancer during pregnancy treated with surgery and adjuvant gemcitabine: A case report and review of the literature.

Gallbladder cancer (GBC) represents the most common biliary tract cancer. Prognosis remains poor with 5-year overall survival rates less than 5% in advanced stages. GBCs are diagnosed more frequently in women, supposedly due to endocrine factors. A 35-year-old woman, diagnosed with a non-metastatic GBC in the 22nd week of gestation, underwent a complete surgical resection 5 weeks later. Adjuvant gemcitabine was administered without complications, temporarily discontinued in the 32nd week to allow childbirth. The patient was disease-free for more than 3 years with ongoing remission at the last visit in July 2022. During the follow-up period, the child had no developmental, cognitive, or other health issues. Malignant tumors occur in about 0.1% of pregnant women, many are treated with chemotherapy. In oncology, the need to deliver optimal treatment in these patients represents a major concern. Both surgery and adjuvant chemotherapy of locally advanced GBC can be performed safely, with certain considerations, in the second trimester of pregnancy

Oncologie [2020 oncology update]

The COVID-19 pandemic that has swept around the world in early 2020 has changed our daily practice and habits. Fortunately, however, 2020 also brings its share of new approaches and therapeutic combinations as well as new therapies. These advances are improving the outcomes and quality of life of our patients across the spectrum of oncological diseases. This article summarises the latest oncological advances and novelties for 2020 in the following tumor entities : lung, breast, digestive, gynecological, urological and ENT

Quantitative verification of implantable cardiac pacemakers over hybrid heart models

We develop a model-based framework which supports approximate quantitative verification of implantable cardiac pacemaker models over hybrid heart models. The framework is based on hybrid input–output automata and can be instantiated with user-specified pacemaker and heart models. For the specifications, we identify two property patterns which are tailored to the verification of pacemakers: “can the pacemaker maintain a normal heart behaviour?” and “what is the energy level of the battery after t time units?”. We implement the framework in Simulink based on the discrete-time simulation semantics and endow it with a range of basic and advanced quantitative property checks. The advanced property checks include the correction of pacemaker mediated Tachycardia and how the noise on sensor leads influences the pacing level. We demonstrate the usefulness of the framework for safety assurance of pacemaker software by instantiating it with two hybrid heart models and verifying a number of correctness properties with encouraging experimental results

Verification of linear duration properties over continuous-time markov chains

Stochastic modeling and algorithmic verification techniques have been proved useful in analyzing and detecting unusual trends in performance and energy usage of systems such as power management controllers and wireless sensor devices. Many important properties are dependent on the cumulated time that the device spends in certain states, possibly intermittently. We study the problem of verifying continuoustime Markov chains (CTMCs) against linear duration properties (LDP), i.e. properties stated as conjunctions of linear constraints over the total duration of time spent in states that satisfy a given property. We identify two classes of LDP properties, eventuality duration properties (EDP) and invariance duration properties (IDP), respectively referring to the reachability of a set of goal states, within a time bound; and the continuous satisfaction of a duration property over an execution path. The central question that we address is how to compute the probability of the set of infinite timed paths of the CTMC that satisfy a given LDP. We present algorithms to approximate these probabilities up to a given precision, stating their complexity and error bounds. The algorithms mainly employ an adaptation of uniformization and the computation of volumes of multi-dimensional integrals under systems of linear constraints, together with different mechanisms to bound the errors. Copyright 2012 ACM

Verification of Linear Duration Properties over Continuous Time Markov Chains

Stochastic modeling and algorithmic verification techniques have been proved useful in analyzing and detecting unusual trends in performance and energy usage of systems such as power management controllers and wireless sensor devices. Many important properties are dependent on the cumulated time that the device spends in certain states, possibly intermittently. We study the problem of verifying continuoustime Markov chains (CTMCs) against linear duration properties (LDP), i.e. properties stated as conjunctions of linear constraints over the total duration of time spent in states that satisfy a given property. We identify two classes of LDP properties, eventuality duration properties (EDP) and invariance duration properties (IDP), respectively referring to the reachability of a set of goal states, within a time bound; and the continuous satisfaction of a duration property over an execution path. The central question that we address is how to compute the probability of the set of infinite timed paths of the CTMC that satisfy a given LDP. We present algorithms to approximate these probabilities up to a given precision, stating their complexity and error bounds. The algorithms mainly employ an adaptation of uniformization and the computation of volumes of multi-dimensional integrals under systems of linear constraints, together with different mechanisms to bound the errors. Copyright 2012 ACM