Endoscopic management of combined malignant biliary and gastric outlet obstruction

Patients with periampullary cancer or gastric cancer often develop malignant biliary obstruction (MBO) and gastric outlet obstruction (GOO), and combined MBO and GOO is not rare in these patients. Combined MBO and GOO is classified by its location and sequence, and treatment strategy can be affected by this classification. Historically, palliative surgery, hepaticojejunostomy and gastrojejunostomy were carried out, but the current standard treatment is combined transpapillary stent and duodenal stent placement. Although a high technical success rate is reported, the procedure can be technically difficult and duodenobiliary reflux with subsequent cholangitis is common after double stenting. Recent development of endoscopic ultrasound (EUS)‐guided procedures enables the management of MBO as well as GOO under EUS guidance. EUS‐guided biliary drainage is now increasingly reported as an alternative to percutaneous transhepatic biliary drainage in failed endoscopic retrograde cholangiopancreatography (ERCP), and GOO is one of the major reasons for failed ERCP. In addition to EUS‐guided biliary drainage, the feasibility of EUS‐guided double‐balloon‐occluded gastrojejunostomy bypass for MBO was recently reported, and EUS‐guided double stenting can potentially become the treatment of choice in the future. However, as each procedure has its advantages and disadvantages, treatment strategy should be selected based on the type of obstruction and the prognosis and performance status of the patient.     

Use of fixed contact-sensitive monolayers for identification and separation of normal from neoplastic cells

Summary Confluent monolayers of a contact-sensitive Balb/c 3T3 cell line were fixed with 3% glutarladehyde to produce fixed contact-sensitive plates (F-CSPs). The growth of first passage human fibroblasts and neoplastic cells superinoculated onto F-CSPs was then compared with the growth of these cells on plastic culture plates. [³H]-thymidine (TdR) incorporation by fibroblasts on Day 3 after inoculation onto F-CSPs was lower than after inoculation onto plastic plates. The [³H]TdR incorporation ratio (Day 7/Day 3) of fibroblasts grown on F-CSPs was also lower than that of cells grown on plastic plates. Moreover, both the absolute [³H]TdR incorporation and the [³H]TdR incorporation ratio of first passage fibroblasts were lower than those of contact-sensitive fibroblast cell lines (10T1/2 and 3Y1) grown on F-CSPs. These results indicated that the attachment and proliferation of first passage human fibroblasts on F-CSPs were both very poor. In contrast, first passage human neoplastic cells (K-M and Br-M cells) showed greater attachment and proliferation on F-CSPs than on plastic plates. On Day 7 after inoculation, the growth ratio of these neoplastic cells vs. that of first passage fibroblasts was approximately 34-fold higher on F-CSPs than on plastic plates. On F-CSPs, first passage human fibroblasts exhibited contact sensitivity and did not proliferate, whereas neoplastic cells continued to grow because they lacked contact sensitivity. This differential growth of cells on F-CSPs may provide a method of separating normal and malignant cells from primary human carcinoma specimens.     

A novel pathogenic variant p.Asp797Val in IFIH1 in a Japanese boy with overlapping Singleton-Merten syndrome and Aicardi-Goutières syndrome

Pathogenic-activating variants of interferon induced with Helicase C domain 1 (IFIH1) cause Singleton-Merten (S-M) syndrome, which accompanies acro-osteolysis, loss of permanent teeth, and aortic calcification, as well as causing Aicardi-Goutières (A-G) syndrome, which shows progressive encephalopathy, spastic paraplegia, and calcification of basal ganglia. Recently, patients with overlapping syndromes presenting with features of S-M syndrome and A-G syndrome were reported. However, progression of clinical features of this condition has not been fully understood. We report a Japanese boy with a novel pathogenic IFIH1 variant who presented with clinical features of S-M syndrome and A-G syndrome.     

Medical,welfare, and educational challenges and psychological distress in parents caring for an individual with 22q11.2 deletion syndrome: A cross-sectional survey in Japan

Parents of children with 22q11.2 deletion syndrome (22q11DS) experience distress not only due to multimorbidity in the patients, but also due to professionals' lack of understanding about 22q11DS and insufficient support systems. This study investigated relationships between medical, welfare, and educational challenges and parental psychological distress. A cross-sectional survey was conducted on primary caregivers of children with 22q11DS. Participants included 125 parents (114 mothers, 91.2%; average age = 44.3 years) who reported their challenges, psychological distress, and child's comorbidities of 22q11DS. Results showed that the difficulty in going to multiple medical institutions (β = 0.181, p < 0.05) and lack of understanding by welfare staff and insufficient welfare support systems for 22q11DS (β = 0.220–0.316, all p < 0.05) were associated with parental psychological distress, even after adjusting for child's comorbidities. In the subsample of parents whose child attended an educational institution, inadequate management in classroom and mismatch between service and users in educational settings were associated with psychological distress (β = 0.222–0.296, all p < 0.05). This study reveals the importance of assessing not only severity of comorbidities in 22q11DS, but also the medical, welfare, and educational challenges for parental mental health.