ホウシャセン チリョウ ガ コウカテキ デ アッタ チョクチョウナイ ブンピツ サイボウ ガン ノ 1 レイ

A 54-year-old woman was seen at the hospital because of anal bleeding. Colonoscopy examination showed a type 2 tumor in the lower rectum and the histological diagnosis from the biopsy specimen was undifferenciated adenocarcinoma. Abdomino-perineal amputation of the rectum were performed. The resected specimen was positive for synaptophysin stain immunohistochemically and we diagnosed it as an endocrine cell carcinoma. We underwent adjuvant chemotherapy by bolus CPT-11, and the post operative course was uneventful. Intra-pelvic recurrence was observed 15 months after operation, and further 4 months later, metastasis developed around the pancreas. And we noticed the tumor in supraclavicular region 21 months after operation. The tumor was sensitive to chemotherapy, but continued to progress. So we underwent radiotherapy for each lesion. The lesion treated with radiotherapy were controlled until she died of cancer, 31 months after the operation. As a result of autopsy, an exellent effect of radiotherapy was confirmed

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (<65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency < 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

Hepatobiliary cystadenoma exhibiting morphologic changes from simple hepatic cyst shown by 11-year follow up imagings

<p>Abstract</p> <p>Background</p> <p>A long-term follow up case of hepatobiliary cystadenoma originating from simple hepatic cyst is rare.</p> <p>Case presentation</p> <p>We report a case of progressive morphologic changes from simple hepatic cyst to hepatobiliary cystadenoma by 11 – year follow up imaging. A 25-year-old man visited our hospital in 1993 for a simple hepatic cyst. The cyst was located in the left lobe of the liver, was 6 cm in diameter, and did not exhibit calcification, septa or papillary projections. No surgical treatment was performed, although the cyst was observed to gradually enlarge upon subsequent examination. The patient was admitted to our hospital in 2004 due to epigastralgia. Re-examination of the simple hepatic cyst revealed mounting calcification and septa. Abdominal CT on admission revealed a hepatic cyst over 10 cm in diameter and a high-density area within the thickened wall. MRI revealed a mass of low intensity and partly high intensity on a T1-weighted image. Abdominal angiography revealed hypovascular tumor. The serum levels of AST and ALT were elevated slightly, but tumor markers were within normal ranges. Left lobectomy of the liver was performed with diagnosis of hepatobiliary cystadenoma or hepatobiliary cystadenocarcinoma. The resected specimen had a solid component with papillary projections and the cyst was filled with liquid-like muddy bile. Histologically, the inner layer of the cyst was lined with columnar epithelium showing mild grade dysplasia. On the basis of these findings, hepatobiliary cystadenoma was diagnosed.</p> <p>Conclusion</p> <p>We believe this case provides evidence of a simple hepatic cyst gradually changing into hepatobiliary cystadenoma.</p

チュウスイ ゲンパツ フクゴウガタ セン シンケイ ナイブンピツ ガン ノ イチチケンレイ

A５２-year-old man visited our hospital because of epigastralgia. The colonoscopic examination revealed an about ４cm-protruded lesion like SMT on the appendix and findings of the biopsy specimen were compatible with the disgnosis of signet ring cell carcinoma. The primary lesion was unknown by upper gastrointestinal endoscopy, CT and PET, and the tumor markers were normal revel. At laparotomy, severe peritoneal metastasis was revealed in the abdominal cavity, especially appendix. Severe stenosis of ileocecum was found, so we conducted ileocecal resection. The histopathological diagnosis was primary signet ring cell caicinoma of appendix, SE, N２, M０, P３, pStage Ⅳ. Postoperatively mFOLFOX was started, but allergic reaction was seen after１cycle. We started Panitumumab/CPT-１１and the patient attended our emergency department with shivering chill and fever on treatment day１０. The next day he became shock state and CT revealed free air. Operation might not save his life and we started supportive care. He died on the day. The cause of his death was peritonitis by cancer perforation

Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana

We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is ~32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene