Influence of NUDT15 variants on hematological pictures of patients with inflammatory bowel disease treated with thiopurines

AIM The single nucleotide polymorphism(SNP) c.415C>T in exon 3 of NUDT15 affects thiopurine-induced leukopenia in Asian patients with Crohn's disease. Meanwhile, three additional genetic variants of NUDT15 were reported in patients with acute lymphoblastic leukemia. We evaluated the effects of these additional genetic variants of NUDT15 in patients with inflammatory bowel disease(IBD) treated with thiopurines.METHODS Ninety-six Japanese patients with IBD were enrolled. Genotyping for the NUDT15 and TPMT genes was performed using Custom Taq Man SNP genotyping assays or Sanger sequencing. The changes in white blood cell(WBC) count, mean corpuscular volume(MCV), platelet count, hemoglobin, CRP, amylase, albumin, AST, ALT, and ESR were evaluated.RESULTS Genetic variants of exon 1 and exon 3 of NUDT15 were identified in 24 of 96 patients(25.0%). C.52G > A and c.36_37 insG GAGTC in exon 1 were found in three patients each. All three patients with c.36_37 insG GAGTC in exon 1 were heterozygotes of p.Arg139 Cys in exon 3. Eighteen patients had p.Arg139 Cys in exon 3 alone. The WBC count gradually decreased after initiation of thiopurine treatment in the mutated cases(n = 24), and was significantly lower at 6, 8, 10, and 16 wk(P = 0.0271, 0.0037, 0.0051, and 0.0185, respectively). The WBC counts were also evaluated in patients with and without prednisolone treatment. In the patients with prednisolone treatment, the WBC count tended to show a greater decrease in the mutated cases, with significant differences at 8 and 10 wk(P = 0.012 and 0.029, respectively). In the patients without prednisolone treatment, the WBC count was significantly lower at 2, 4, 8, and 14 wk in mutated cases(P = 0.0196, 0.0182, 0.0237 and 0.0241, respectively). MCV increased after starting thiopurine treatment in the mutated cases, and was significantly higher at 10 wk(P = 0.0085). Platelet count, hemoglobin, CRP, amylase, albumin, AST, ALT and ESR did not differ significantly between the wildtype and mutated cases. TPMT mutations were not found in any of the patients.CONCLUSION Mutations in exon 1 of NUDT15 also affect thiopurineinduced leukopenia in patients with IBD. To discuss thiopurine-induced leukopenia in more detail, investigation of SNPs in both exon 1 and exon 3 of NUDT15 is needed.

Endoscopic reduction of colocolonic intussusception due to metastatic malignant melanoma:A case report

BACKGROUND Intussusception rarely causes intestinal obstruction in adults.Metastatic malignant melanoma is the main cause of intussusception of the small intestine among adults.However,malignant melanoma rarely causes intussusception of the colorectum.Moreover,emergent surgery is usually performed for such cases.Here,we report a case of a patient with colocolonic intussusception caused by a malignant melanoma,for which endoscopic reduction and elective surgery were performed.CASE SUMMARY The patient was a 64-year-old woman who underwent multiple surgeries and received chemotherapy and immunotherapy for a malignant melanoma.During immunotherapy,she had abdominal pain,diarrhea,and bloody stool.Physical examination and laboratory studies did not reveal any findings that warranted emergent surgery.Computed tomography revealed intussusception in the descending colon without intestinal necrosis and perforation.Intussusception was reduced endoscopically,and elective surgery was performed.CONCLUSION This report suggests that endoscopic reduction and elective surgery constitute a treatment option for colocolonic intussusception of metastatic malignant melanomas.