DDX24 Mutations Associated With Malformations of Major Vessels to the Viscera.

Vascular malformations present diagnostic and treatment challenges. In particular, malformations of vessels to the viscera are often diagnosed late or incorrectly due to the insidious onset and deep location of the disease. Therefore, a better knowledge of the genetic mutations underlying such diseases is needed. Here, we evaluated a four-generation family carrying vascular malformations of major vessels that affect multiple organs, which we named "multiorgan venous and lymphatic defect" (MOVLD) syndrome. Genetic analyses identified an association between a mutation in DEAD-box helicase 24 (DDX24), a gene for which the function is largely unknown, and MOVLD. Next, we screened 161 patients with sporadic vascular malformations of similar phenotype to our MOVLD family and found the same mutation or one of the two additional DDX24 mutations in 26 cases. Structural modeling revealed that two of the mutations are located within the adenosine triphosphate-binding domain of DDX24. Knockdown of DDX24 expression in endothelial cells resulted in elevated migration and tube formation. Transcriptomic analysis linked DDX24 to vascular system-related functions. Conclusion: Our results provide a link between DDX24 and vascular malformation and indicate a crucial role for DDX24 in endothelial cell functions; these findings create an opportunity for genetic diagnosis and therapeutic targeting of malformations of vessels to the viscera.

Percutaneous transhepatic intrahepatic portosystemic shunt for variceal bleeding with chronic portal vein occlusion after splenectomy.

OBJECTIVES: The purpose of this study was to introduce a modified transjugular intrahepatic portosystemic shunt (TIPS), a percutaneous transhepatic intrahepatic portosystemic shunt (PTIPS), and to evaluate its feasibility and efficacy in patients with variceal bleeding with chronic portal vein occlusion (CPVO) after splenectomy. METHODS: Twenty-four cirrhotic patients with CPVO after splenectomy who received PTIPS between 2010 and 2015 were included in this retrospective study. The indication was elective control of variceal bleeding. Success rates, effectiveness and complications were evaluated, with comparison of the pre- and post-portosystemic pressure gradient (PPG). Patients' clinical outcomes and shunt patency were followed periodically. RESULTS: PTIPS was successfully placed in 22 patients (91.7%) and failed in two. The mean PPG fell from 22.0 ± 4.9 mmHg to 10.6 ± 1.6 mmHg after successful PTIPS (p < 0.05). No fatal procedural complications occurred. During the median follow-up of 29 months, shunt dysfunction occurred in five cases and hepatic encephalopathy in four cases. Three patients died because of rebleeding, hepatic failure and pulmonary disease, respectively. The other patients remained asymptomatic and the shunts patent. CONCLUSIONS: We conclude that PTIPS, as a modified TIPS procedure with a high success rate, is safe and effective for variceal bleeding with CPVO after splenectomy. KEY POINTS: • Portal vein occlusion used to be contraindication to transjugular intrahepatic portosystemic shunt. • Portal vein thrombosis is common in patients with previous splenectomy. • We developed a new method, percutaneous transhepatic intrahepatic portosystemic shunt (PTIPS). • PTIPS is feasible in patients with portal vein thrombosis and splenectomy. • PTIPS is effective and safe for these kind of complicated portal hypertension.

[Clinical study of percutaneous transhepatic intrahepatic portosystemic shunt].

OBJECTIVE: To introduce an innovative procedure for portal hypertension with preliminary results and assess the technical feasibility and efficacy of portosystemic shunt creation through percutaneous transhepatic approach with its potential clinical significance. METHODS: Between November 2009 and January 2011, 8 patients with complicated portal hypertension underwent percutaneous transhepatic intrahepatic portosystemic shunt (PTIPS). The severity of liver disease was Child's A (n = 2), Child's B (n = 3) and Child's C (n = 3). Under fluoroscopic guidance, portal vein (PV) was punctured with a 22-gauge Chiba needle. A 0.018-inch guidewire was advanced through the needle into PV lumen. The needle was exchanged and a 7-French sheath inserted over the wire. Then retrohepatic inferior vena cava (RIVC) or hepatic vein (HV) was punctured with a 20-gauge, 20-cm Chiba needle through sheath. Another 0.018-inch guidewire was advanced through the needle into right internal jugular vein and then snared out of body. A 0.035-inch, 260-cm-long stiff shaft wire was then introduced through the transjugular sheath and manipulated into main portal vein (MPV) and then into superior mesenteric vein (SMV). Afterward the PTIPS procedure was completed in the standard transjugular fashion. RESULTS: The procedure was technically successful in all patients. And effective portal decompression and free antegrade shunt flow were achieved. The mean portal pressure gradient decreased from 31.0 ± 4.3 to 18.9 ± 2.7 mm Hg before and after PTIPS creation respectively and the difference was significant statistically (P < 0.01). Among 8 patients, 1 developed hepatic coma and died after 5 days while the other 7 patients survived. The median follow-up period was 9 months (range: 2 - 20). Among 5 patients with PTIPS created for bleeding varices, no recurrent bleeding occurred during the follow-up period. For the patient with diffuse portal vein thrombosis, the clinical symptoms disappeared after PTIPS and computed tomography (CT) showed the shunt was occluded after 4 months. One patient with refractory ascites had a recurrence of abdominal distention after 2 months. There was a stenotic shunt on CT. Cure was achieved by replanting a stent in MPV. CONCLUSION: PTIPS is both safe and effective for the treatment of portal hypertension with exceptionally challenging anatomy. It is an available supplement for transjugular intrahepatic portosystemic shunt.

Evolution of associating liver partition and portal vein ligation for staged hepatectomy: Simpler, safer and equally effective methods.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been recently demonstrated as a method to induce rapid and extensive hypertrophy within a short time and has been employed for a variety of primary and metastatic liver tumors. However, controversies remain due to its high morbidity and mortality. To enable safer surgery, liver surgeons have searched for better technical modifications, such as partial ALPPS, mini-ALPPS, minimally invasive ALPPS, and Terminal branches portal vein Embolization Liver Partition for Planned hepatectomy (TELPP). It seems that TELPP is very promising, because it has the main advantage of ALPPS - the rapid increase of future liver remnant volume, but the morbidity and mortality are much lower because only one surgical operation is required.