Novel ACOX1 mutations in two siblings with peroxisomal acyl-CoA oxidase deficiency

Peroxisomal acyl-CoA oxidase (ACOX1) deficiency is a rare autosomal recessive single enzyme deficiency characterized by hypotonia, seizures, failure to thrive, developmental delay, and neurological regression starting from approximately 3 years of age.Here, we report two siblings with ACOX1 deficiency born to non-consanguineous Japanese parents. They showed mild global developmental delay from infancy and began to regress at 5 years 10 months and 5 years 6 months of age respectively. They gradually manifested with cerebellar ataxia, dysarthria, pyramidal signs, and dysphasia. Brain MRI revealed T2 high-intensity areas in the cerebellar white matter, bilateral middle cerebellar peduncle, and transverse tracts of the pons, followed by progressive atrophy of these areas.Intriguingly, the ratios of C24:0, C25:0, and C26:0 to C22:0 in plasma, which usually increase in ACOX1 deficiency were within normal ranges in both patients. On the other hand, whole exome sequencing revealed novel compound heterozygous variants in ACOX1: a frameshift variant (c.160delC:p.Leu54Serfs*18) and a missense variant (c.1259 T > C:p.Phe420Ser). The plasma concentration of individual very long chain fatty acids (C24:0, C25:0, and C26:0) was elevated, and we found that peroxisomes in fibroblasts of the patients were larger in size and fewer in number as previously reported in patients with ACOX1 deficiency. Furthermore, the C24:0 β-oxidation activity was dramatically reduced.Our findings suggest that the elevation of individual plasma very long chain fatty acids concentration, genetic analysis including whole exome analysis, and biochemical studies on the patient’s fibroblasts should be considered for the correct diagnosis of ACOX1 deficiency.     

Gastrointestinal tract metastasis of lung cancer: The PD-L1 expression and correlated clinicopathological variables

The gastrointestinal tract is a rare site for metastatic lung cancer. Programmed cell death-ligand 1 (PD-L1) expression in lung cancer is a biomarker for the response to anti-PD-1/PD-L1 therapy. We investigated clinicopathological features and PD-L1 expression in 25 gastrointestinal metastatic tumors from the lung and primary adenocarcinoma of the small bowel. The small bowel was the most common site (16/25; 64%) of gastrointestinal tract lung cancer metastasis. A total of 19 (76%) of the gastrointestinal metastasis showed PD-L1 expression in ≥5% of tumor cells, with 14 (56%) showing high expression levels (≥50%). In contrast, 21 (84%) expressed PD-L1 in ≥5% immune cells, including 4 (16%) showing a high expression levels (≥50%). The PD-L1 expression on tumor cells and immune cells in primary lung cancer and corresponding gastrointestinal metastasis was concordant in 13 (68%) and 11 (58%) of the 19 paired cases, respectively. Small-bowel metastasis of lung cancer was characterized by a higher incidence of perforation (31% vs. 0%), ulcerated mass (83% vs. 60%), and neoplastic PD-L1 expression (75% vs. 0%) compared to primary small-bowel adenocarcinoma. Gastrointestinal metastasis from lung cancer might be a potential target for immune checkpoint inhibitor therapy, given its high expression of PD-L1.     

Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis

Odontology - There is no conclusive evidence regarding a causal relationship between periodontitis and atherosclerosis. In this study, we examined the microbiome in the oral cavity and atheromatous...     

Determining Timing of Hepatectomy for Colorectal Cancer with Distant Metastasis According to Imaging-Based Tumor Shrinkage Ratio

Background: The optimal timing of surgical resection of liver metastasis remains controversial, and guidelines regarding the upper limits of operative indications have not yet been defined. Surgical indication for metastasis from colorectal cancer (CLM) based on results of preoperative chemotherapy and RNF8 was investigated. Methods: Differences in CLM size on CT were evaluated as shrinkage rate/day by dividing tumor shrinkage rates by the interval in days between CT. Levels of RNF8 of resected colorectal cancer and CLM frozen specimen were detected. Results: When the cut line for shrinkage rate at 12 weeks was set at 0.35%, disease-free survival was significantly better in patients with a shrinkage rate >0.35% vs. ≤0.35% (p=0.003). RNF8 expression was significantly higher in Tis (p=0.001). In liver metastasis, RNF8 expression level was significantly lower in patients with partial response to FOLFOX than with stable disease, (p=0.017). Conclusions: A strategy of FOLFOX administration for 12 weeks to patients with low RNF8 expression and hepatectomy planned after 4 weeks rest may be accepted as the best therapeutic option for treating CLM.     

A Single Case of Single-Port Access Laparoscopic Appendectomy During the Puerperium

Laparoscopic appendectomy is now widely practiced for the treatment of acute appendicitis. As result of increased demand for minimally invasive surgery, single-incision access was introduced and is being performed in various abdominal surgeries. Conventional laparoscopic appendectomy (LA) is gradually being performed in pregnant women. A 33-year-old woman was referred to our department at 39 weeks and 1 day of gestation due to abdominal pain. She was aware of her gastroepiploic pain even after the delivery. Though it was past 2 days, she was not recovering from right lower abdominal pain, so she was transferred to the Department of Gynecology at our hospital on the same day. Although an antibiotic was administered, the right abdominal pain did not improve, and she was referred to our department from the Department of Gynecology. We performed single-port LA (SP-LA). The total operation time was 63 minutes, and the estimated blood loss was 0 mL. She was discharged with no complications on postoperative day 7. We report our initial experience with single-port LA (SP-LA) using the glove technique for treatment of acute appendicitis in a postpartum woman. SP-LA using the glove technique was performed successfully during the puerperium without prolongation of operation time. This approach is less invasive, offers a much better cosmetic result than with conventional methods, and can be performed safely and at low cost.Key words: PLA (single-port laparoscopic appendectomy), PuerperiumThe advantages of laparoscopic appendectomy (LA) over open appendectomy (OA) are widely known and include decreased pain, shorter convalescence, and earlier return to work. Especially, LA is advantageous for treating acute appendicitis in pregnant women. Because the appendix of a pregnant woman is shifted from its normal position, OA may leave a larger operative scar than normal. In recent years, efforts of laparoscopic surgeons have resulted in a reduction in both the diameter of the access ports and the number of ports needed.¹ In addition, natural orifice transluminal endoscopic surgery (NOTES) is being developed as another form of minimally invasive surgery.² As a part of this process, the single-incision laparoscopic surgery (SILS) technique is presently being developed for various laparoscopic surgeries.³ SILS is a virtually scarless technique in which the single-port access site is hidden in the umbilicus. We think that the primary advantage of single-port laparoscopic appendectomy (SP-LA) is the superior cosmetic result compared with multi-port access LA. We report a very rare case in which SP-LA was performed to treat acute appendicitis during the puerperium. This approach is less invasive, offers a much better cosmetic result than with conventional methods, and can be performed safely and at low cost.