Impact of classical and basal-like molecular subtypes on overall survival in resected pancreatic cancer in the SPACIOUS-2 multicentre study.

BACKGROUND: The recently identified classical and basal-like molecular subtypes of pancreatic cancer impact on overall survival (OS). However, the added value of routine subtyping in both clinical practice and randomized trials is still unclear, as most studies do not consider clinicopathological parameters. This study examined the clinical prognostic value of molecular subtyping in patients with resected pancreatic cancer. METHODS: Subtypes were determined on fresh-frozen resected pancreatic cancer samples from three Dutch centres using the Purity Independent Subtyping of Tumours classification. Patient, treatment, and histopathological variables were compared between subtypes. The prognostic value of subtyping in (simulated) pre- and postoperative settings was assessed using Kaplan-Meier and Cox regression analyses. RESULTS: Of 199 patients with resected pancreatic cancer, 164 (82.4 per cent) were classified as the classical and 35 (17.6 per cent) as the basal-like subtype. Patients with a basal-like subtype had worse OS (11 versus 16 months (HR 1.49, 95 per cent c.i. 1.03 to 2.15; P = 0.035)) than patients with a classical subtype. In multivariable Cox regression analysis, including only clinical variables, the basal-like subtype was a statistically significant predictor for poor OS (HR 1.61, 95 per cent c.i. 1.11 to 2.34; P = 0.013). When histopathological variables were added to this model, the prognostic value of subtyping decreased (HR 1.49, 95 per cent c.i. 1.01 to 2.19; P = 0.045). CONCLUSION: The basal-like subtype was associated with worse OS in patients with resected pancreatic cancer. Adding molecular classification to inform on tumor biology may be used in patient stratification.

Muslim Jurisprudence on Withdrawing Treatment from Incurable Patients: A Directed Content Analysis of the Papers of the Islamic Fiqh Council of the Muslim World League.

This study investigates the views of contemporary Muslim jurists about withdrawing treatment of the terminally ill. Its aim is threefold. Firstly, it analyses jurists' views concerning core themes within the process of withdrawing treatment. Secondly, it provides insight into fatwas about withdrawing treatment. Thirdly, it compares these views with current medical standards in Europe and the Atlantic world on withdrawing treatment. The data consisted of six papers by Muslim jurists presented at the conference of the Islamic Fiqh Council in 2015. We conducted a directed content analysis (DCA) through a predetermined framework and compiled an overview of all previous fatwas referred to in the papers, which are also analysed. The results show that the general consensus is that if health cannot be restored, treatment may be withdrawn at the request of the patient and/or his family or on the initiative of the doctor. The accompanying fatwa emphasizes the importance of life-prolonging treatment if this does not harm the patient. It becomes apparent in the fatwa that the doctor has the monopoly in decision-making, which is inconsistent with current medical standards in Europe. Managing disclosure in view of the importance of maintaining the hope of Muslim patients may challenge the doctor's obligation to share a diagnosis with them.

Free-breathing motion corrected magnetic resonance elastography of the abdomen.

Background: Magnetic resonance elastography (MRE) is a non-invasive method to measure the viscoelastic properties of tissue and has been applied in multiple abdominal organs. However, abdominal MRE suffers from detrimental breathing motion causing misalignment of structures between repeated acquisitions for different MRE dimensions (e.g., motion encoding directions and wave phase offsets). This study investigated motion correction strategies to resolve all breathing motion on sagittal free-breathing MRE acquisitions in a phantom, in healthy volunteers and showed feasibility in patients. Methods: First, in silico experiments were performed on a static phantom dataset with simulated motion. Second, eight healthy volunteers underwent two sagittal MRE acquisitions in the pancreas and right kidney. The multi-frequency free-breathing spin-echo echo-planar-imaging (SE-EPI) MRE consisted of four frequencies (30, 40, 50, 60 Hz), eight wave-phase offsets, with 3 mm3 isotropic voxel size. Following data re-sorting in different number of motion states (4 till 12) based on respiratory waveform signal, three intensity-based registration methods (monomodal, multimodal, and phase correlation) and non-rigid local registration were compared. A ranking method was used to determine the best registration method, based on seven signal-to-noise and image quality measures. Repeatability was assessed for no motion correction (Original) and the best performing method (Best) using Bland-Altman analysis. Lastly, the best motion correction method was compared to no motion correction on patient MRE data [pancreatic ductal adenocarcinoma (PDAC, n=5) and metabolic dysfunction-associated steatotic liver disease (MASLD) (n=1)]. Results: In silico experiments showed a deviation of shear wave speed (SWS) with simulated motion to the ground truth, which was (partially) resolved using motion correction. In healthy volunteers ranking resulted in the best motion correction method of monomodal registration using nine motion states, while no motion correction was ranked last. Limits of agreement were (-0.18, 0.14), and (-0.25, 0.18) m/s for Best and Original, respectively. Using motion correction in patients resulted in a significant increase in SWS in the pancreas (Original: 1.39±0.10 and Best: 1.50±0.17 m/s). After motion correction PDAC had a mean SWS of 1.56±0.27 m/s (Original: 1.42±0.25 m/s). The fibrotic liver mean SWS was 2.07±0.20 m/s (Original: 2.12±0.18 m/s). Conclusions: Motion correction in sagittal free-breathing abdominal MRE results in improved data quality, inversion precision, repeatability, and is feasible in patients.