Search

Background: The management of invasive intraductal papillary mucinous cystic neoplasm (I-IPMN) does not differ from de novo pancreatic ductal adenocarcinoma (PDAC); however, I-IPMNs are debated to have better prognosis. Despite being managed similarly to PDAC, no data are available on the response of I-IPMN to neoadjuvant chemotherapy. Methods: All patients undergoing pancreatic resection for a pancreatic adenocarcinoma from 2011 to 2022 were included. The PDAC and I-IPMN cohorts were compared to evaluate response to neoadjuvant therapy (NAT) and overall survival (OS). Results: This study included 1052 PDAC patients and 105 I-IPMN patients. NAT was performed in 25% of I-IPMN patients and 65% of PDAC patients. I-IPMN showed a similar pattern of pathological response to NAT compared with PDAC (p = 0.231). Furthermore, positron emission tomography (PET) response (71% vs. 61%; p = 0.447), CA19.9 normalization (85% vs. 76%, p = 0.290), and radiological response (32% vs. 37%, p = 0.628) were comparable between I-IPMN and PDAC. A significantly higher OS and disease-free survival (DFS) of I-IPMN was denoted by Kaplan–Meier analysis, with a p-value of < 0.001 in both plots. In a multivariate analysis, I-IPMN histology was independently associated with lower risk of recurrence and death. Conclusions: I-IPMN patients have a longer OS and DFS after surgical treatment when compared with PDAC patients. The more favorable oncologic outcome of I-IPMNs does not seem to be related to early detection, as I-IPMN histological subclass is independently associated with a lower risk of disease recurrence. Moreover, neoadjuvant effect on I-IPMN was non-inferior to PDAC in terms of pathological, CA19.9, PET, and radiological response and thus can be considered in selected patients.

Item does not contain fulltext, Barth syndrome is known as a highly recognizable X-linked disorder typically presenting with the three hallmarks: (left ventricular non-compaction) cardiomyopathy, neutropenia, and 3-methylglutaconic aciduria. Furthermore, growth retardation, mild skeletal myopathy, and specific facial features as well as mitochondrial dysfunction in muscle are frequently seen. Underlying mutations are found in TAZ and lead to defective cardiolipin remodeling.Here, we report atypical clinical manifestations of TAZ mutations in two male patients initially presenting with growth retardation and very mild skeletal myopathy. As other phenotypic hallmarks were missing, Barth syndrome had not been suspected in these patients. One of them has been incidentally diagnosed in the frame of an in-depth cardiolipin research analysis, while the underlying genetic defect was unexpectedly identified in the second one by exome sequencing. CONCLUSION: These cases underline that TAZ mutations might well be an underdiagnosed cause of skeletal myopathy and growth retardation and do not necessarily manifest with the full clinical picture of Barth syndrome.

Item does not contain fulltext, Leigh syndrome (MIM 25600), also known as infantile subacute necrotizing encephalomyelopathy, is a neurodegenerative disorder with characteristic bilateral symmetric lesions in basal ganglia and subcortical brain regions. It is commonly associated with systemic cytochrome c oxidase (COX) deficiency and mutations in the SURF1 gene (MIM 185620), encoding a putative assembly or maintenance factor of COX. The clinical course is dominated by neurodevelopmental regression, brain stem, and basal ganglia involvement (e.g., dystonia, apnea) with death often occurring before the age of 10 years. Herein, we present three sisters carrying a previously reported homozygous SURF1 mutation (c.868_869insT) that is predicted to result in a truncated protein with loss of function. Our patients show heterogeneous clinical findings with different distribution patterns of metabolic lesions in brain magnetic resonance imaging (MRI) as well as a Chiari malformation with hydrocephalus in one patient. However, all three siblings show an unusual long survival (12 years and > 16 years). COX activity was not detectable in one patient and strongly reduced in the other two. We discuss these findings with respect to a review of the literature. A total of 15 additional patients with survival > 14 years have been reported so far. Overall, no clear genotype-phenotype correlations are detectable among these patients.