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Introduction: We present a case of a patient with resectable perihilar cholangiocarcinoma (pCCA) who underwent primary metal stenting above the ampulla, followed by a successful surgical resection. Biliary drainage is a crucial step in the preoperative management of pCCA, yet there is no consensus on the optimal approach. Traditional drainage methods involve passing through the ampulla and/or the skin barrier, thereby increasing the risk of bacterial contamination of the biliary tree and secondary cholangitis., Method: A novel drainage technique was utilised in this case. A metal stent was percutaneously placed across the malignant hilar stenosis without external biliary drainage. During the procedure, both guidewires and stents were meticulously prevented from passing through the ampulla. Additionally, percutaneous access to the biliary tree was removed during the index procedure to minimise the risk of biliary colonisation and cholangitis., Results: Following the drainage, bilirubin levels rapidly normalised, and no clinical or biochemical signs of cholangitis were observed. This allowed for rapid and uncomplicated surgical resection., Conclusion: This case illustrates the potential of a novel biliary drainage technique in patients with pCCA. By minimising the risk of biliary colonisation and cholangitis, this approach could potentially improve surgical outcomes.

Operative management of rib fractures has gained significant popularity over the last years, however, it remains a controversial topic, due to the substantial heterogeneity among rib fracture patients with considerable differences in epidemiology. Hence, the present narrative review aims to provide an overview of the treatment and (long-term) outcomes of rib fractures, with an emphasis on the surgical treatment. Nowadays, computed tomography (CT) has been shown to be most practical and sensitive for detecting rib fractures, of which up to 50% is missed on other imaging modalities. Non-operative treatment by patient-tailored multimodal pain management remains the cornerstone. Still, in the presence of-amidst others-chest wall instability or displaced fractures with physiologic derangements, operative treatment is indicated and should be performed within 72 hours after injury. Here, traumatic brain injury (TBI) and pulmonary contusion are no strict contra-indications, while plate osteosynthesis is considered the standard mode for surgical stabilization. To date, surgical stabilization of rib fractures (SSRF) only benefits selected groups of patients, awaiting results of ongoing studies. Future directions may include the sole use of percutaneous cryoablation of the intercostal nerves as part of conservative management, as well as the application of three-dimensional (3D) printing and use of bio-absorbable materials in the surgical treatment of rib fractures., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1832/coif). The special series “Chest Wall Resections and Reconstructions” was commissioned by the editorial office without any funding or sponsorship. J.H.T.D. and E.R.d.L. served as the unpaid Guest Editors of the series. The authors have no other conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

ICF syndrome is a rare autosomal recessive immunoglobulin deficiency, sometimes combined with defective cellular immunity. Other features that are frequently observed in ICF syndrome patients include facial dysmorphism, developmental delay, and recurrent infections. The most diagnostic feature of ICF syndrome is the branching of chromosomes 1, 9, and 16 due to pericentromeric instability. Positional candidate cloning recently discovered the de novo DNA methyltransferase 3B (DNMT3B) as the responsible gene by identifying seven different mutations in nine ICF patients. DNMT3B specifically methylates repeat sequences adjacent to the centromeres of chromosome 1, 9, and 16. Our panel of 14 ICF patients was subjected to mutation analysis in the DNMT3B gene. Mutations in DNMT3B were discovered in only nine of our 14 ICF patients. Moreover, two ICF patients from consanguineous families who did not show autozygosity (i.e. homozygosity by descent) for the DNMT3B locus did not reveal DNMT3B mutations, suggesting genetic heterogeneity for this disease. Mutation analysis revealed 11 different mutations, including seven novel ones: eight different missense mutations, two different nonsense mutations, and a splice-site mutation leading to the insertion of three aa's. The missense mutations occurred in or near the catalytic domain of DNMT3B protein, indicating a possible interference with the normal functioning of the enzyme. However, none of the ICF patients was homozygous for a nonsense allele, suggesting that absence of this enzyme is not compatible with life. Compound heterozygosity for a missense and a nonsense mutation did not seem to correlate with a more severe phenotype., (Copyright 2000 Wiley-Liss, Inc.)

We report a branch site mutation in the gene of the enzyme tyrosine hydroxylase (TH): a -24t > a substitution two bases upstream of the adenosine in the branchpoint sequence (BPS) of intron 11. As normal lariat formation is therefore prevented, alternative splicing takes place; use of the BPS of intron 12 results in skipping of exon 12, whereas the use of a cryptic branch site in intron 11 leads to partial retention of this intron in the mRNA. This leads in both cases to an aberrant protein product. In the one case, skipping of exon 12 results in the absence of 32 amino acids. In the other, retention of 36 nucleotides of intron 11 in the mRNA results in the incorporation of twelve additional amino acids. The functional consequences of this mutation for the patient, who is also heterozygous for another previously identified mutation, become apparent in a severe clinical phenotype.

We describe seven Dutch patients from six families with a slowly progressive, mainly spinal cord syndrome that remained for many years the sole expression of cerebrotendinous xanthomatosis (CTX). MRI demonstrated white matter abnormalities in the lateral and dorsal columns of the spinal cord. Post-mortem examination of one of the patients showed extensive myelin loss in these columns. An array of genotypes was found in these patients. We conclude that 'spinal xanthomatosis' is a clinical and radiological separate entity of CTX that should be included in the differential diagnosis of 'chronic myelopathy'.

Immunodeficiency in association with centromere instability of chromosomes 1, 9, and 16 and facial anomalies (ICF syndrome) is a rare autosomal recessive disorder. ICF patients show marked hypomethylation of their DNA; undermethylation of classical satellites II and III is thought to be associated with the centromere instability. We used DNA from three consanguineous families with a total of four ICF patients and performed a total genome screen, to localize the ICF syndrome gene by homozygosity mapping. One chromosomal region (20q11-q13) was consistently found to be homozygous in ICF patients, whereas all healthy sibs showed a heterozygous pattern. Comparison of the regions of homozygosity in the four ICF patients localized the ICF locus to a 9-cM region between the markers D20S477 and D20S850. Analysis of more families will be required, to refine the map location further. Isolation of the gene associated with the ICF syndrome not only will give insight into the etiology of the ICF syndrome but will also broaden our understanding of DNA methylation processes.

Two types of myoadenylate deaminase (MAD) deficiency have been described, primary or inherited, and secondary or acquired MAD deficiency. In this study, we investigated whether secondary MAD deficiency is indeed acquired or merely coincidental. We demonstrated the same underlying molecular defect, a C34T transition, in both types of deficiency. Furthermore, the same frequency of the mutant MAD allele was found in the general population as in patients with neuromuscular complaints. We therefore conclude that in the Dutch population, secondary MAD deficiency is merely a "coincidental" finding, and that MAD deficiency is a harmless genetic variant.

We report a new mutation in the sterol 27-hydroxylase (CYP 27) gene in a Dutch family with cerebrotendinous xanthomatosis: a G-->A transition in the splice donor site in intron 4. This mutation leads to skipping of exon 4, resulting in a loss of 66 amino acids in the CYP 27 enzyme molecule.

This report concerns two new mutations in the sterol 27-hydroxylase gene in two patients with cerebrotendinous xanthomatosis (CTX). In a Surinam-Creole patient (patient A), a G deletion on position cDNA 546/547 in exon 3 led to a frameshift and the introduction of a premature termination codon. In a Dutch patient (patient B), a C-->T transition at position 496 in exon 3 also led to a premature termination codon. Patient A was homozygous for the mutation, whereas patient B was compound heterozygous, a C-->T transition also being found in exon 6 at position 1204. The two new mutations were confirmed by restriction analysis with the restriction enzymes FokI and MaeI, respectively.

Sequencing of the arylsulfatase A gene in a late infantile metachromatic leukodystrophy patient showed the presence of a 12-bp deletion in exon 2. This deletion was found in a compound heterozygous state with the previously described 287 C-->T transition.