Assessment of Molecular Cytogenetic Methods for the Detection of Chromosomal Abnormalities

Some marker chromosomes and chromosome rearrangements are difficult to identify using G-bands by Giemsa staining after trypsin treatment (G-banding) alone. Molecular cytogenetic techniques, such as spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH), can help to detect chromosomal aberrations precisely. We analyzed the karyotypes in 6 cases of multiple congenital abnormalities and 1 case of spontaneous abortion (case 2). Three cases (cases 1, 6, and 7) had marker chromosomes, and 4 cases (cases 2-5) had chromosomal rearrangements. The karyotypes in cases 1, 2, and 3 were determined using FISH with probes based on the clinical findings and family histories. Spectral karyotyping (SKY) analysis in cases 4-7 showed that this method is useful and saves time. The combination of SKY and FISH analyses defi ned the range of the ring chromosome in case 7. We demonstrated that a combination of G-banding, FISH, and SKY can be applied effectively to the investigation of chromosomal rearrangement and to the detection of marker chromosome origins. We suggest the use of these methods for prenatal diagnosis, in which the inherent time limitations are particularly important

Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations

Patients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR-mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients’ reported outcomes. For patients with NSCLC harboring EGFR-activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients

VNTR polymorphism in the 17th and 20th introns of the RB1 gene in Japanese and its application to genetic counseling in hereditary retinoblastoma

Risk estimation for siblings or offspring is important in genetic counseling of patients with hereditary retinoblastoma. The RB1 gene spans approximately 200 kb in length, containing 27 exons. The use of polymorphic markers within the RB1 gene will eliminate the need of laborious specification of a mutation. The present study determined types and frequencies of VNTR polymorphisms of the 17th and 20th introns of the RB1 gene in 50 unrelated Japanese, using PCR amplification. In the 17th intron VNTR, there were 4 alleles, which ranged from 1400 by to 1550 bp. The most common allele was 1400 bp with a frequency of 73%, and the hetetozygosity rate was 46%. In the 20th intron VNTR, there were at least 9 alleles, wihch ranged from 192 bp to 240 bp. The alleles were more evenly distributed than those of the 17th intron VNTR, and the heterozygosity rate was 64%. These VNTR polymorphisms were successfully applied to the prediction of retinoblastoma and to the determination of parental origin of a chromosome deletion in 3 families with hereditary retinoblastoma. Analysis of VNTR polymorphisms within the RB1 gene proves to be practical and efficient for risk estimation in hereditary retinoblastoma

Neural Text Generation with Artificial Negative Examples to Address Repeating and Dropping Errors

Neural text generation models that are conditioned on a given input (e.g., machine translation and image captioning) are typically trained through maximum likelihood estimation of the target text. However, models trained in this manner often suffer from various types of errors when making subsequent inferences. In this study, we propose suppressing an arbitrary type of error by training the text generation model in a reinforcement learning framework; herein, we use a trainable reward function that can discriminate between references and sentences, containing the targeted type of errors. We create such negative examples by artificially injecting the targeted errors into the references. In the experiments, we focus on two error types; repeated and dropped tokens in model-generated text. The experimental results demonstrate that our method can suppress generation errors, and achieves significant improvements on two machine translation and two image captioning tasks

A case of an advanced renal collecting duct carcinoma in which initial therapeutic effect was achieved with pembrolizumab plus axitinib

Introduction Renal collecting duct carcinoma is often found in advanced cancers and has a poor prognosis. Here, we present the case of symptomatic metastatic collecting duct carcinoma in which we observed an initial therapeutic effect of immune checkpoint inhibitors plus tyrosine kinase inhibitors. Case presentation The patient was a 69‐year‐old male who was referred to our hospital for examination of a right chest tumor and related pain. Contrast‐enhanced computed tomography and tumor biopsy were performed, leading to a diagnosis of collecting duct carcinoma. A combination of pembrolizumab plus axitinib was initiated as first‐line therapy; right chest pain decreased, and tumor shrinkage was observed. Seven months after treatment initiation, tumor progression was noted. Cabozantinib was initiated as second‐line therapy; however, was discontinued due to patient fatigue. The patient died 15 months after the initiation of treatment. Conclusion For symptomatic metastatic collecting duct carcinoma, pembrolizumab plus axitinib may have initial therapeutic effects

Well-differentiated Endocrine Cell Carcinoma of Ileum Treated by Laparoscopy-assisted Surgery : A Case Report

A 72-year-old woman presented at our hospital with a 1-year history of intermittent right lower abdominal pain. Colonoscopic examination revealed a submucosal tumor with a pitted surface in the terminal ileum. Histopathological diagnosis of the carcinoid tumor was made following biopsy. Blood serotonin and urine 5-hydroxy-indoleacetic acid levels were normal, and carcinoid syndrome was not detected. Enhanced abdominal computed tomography scan and 18F-fluorodeoxyglucose positron emission tomography failed to detect multiple lesions, lymph node swelling or distant metastasis. Laparoscopy-assisted ileocecal resection with lymph node dissection was performed. The resected specimen showed a submucosal tumor with a pitted surface 11 x 11 mm in size, located at the terminal ileum. Histopathological examination revealed a well-differentiated endocrine cell carcinoma with an invasion depth to the muscularis propria. Immunohistochemical analysis showed the tumor cells to be chromogranin A and CD56-positive. The patient had no sign of recurrence for 16 months