Clinical pharmacokinetics of oxaliplatin in a hemodialysis patient with advanced gastric cancer

We administered FOLFOX (oxaliplatin (L-OHP) plus infusional 5-fluorouracil (5-FU) and leucovorin) to an hemodialysis (HD) patient with advanced gastric cancer (AGC), and investigated pharmacokinetics (PKs) and dialyzability of L-OHP. The patient was a 54-year-old Japanese man with a diagnosis of inoperable AGC. FOLFOX was instituted 3?h prior to the start of a 4?h HD period with the L-OHP and 5-FU doses reduced by 50% for the first cycle, and 30% reduced dose was administered for the second cycle. We performed an analysis of the PKs of L-OHP during these two cycles. Volume of distribution and area under the curve of the 30% reduced L-OHP dose were 56.7?L and 30.0?μg·h/mL, respectively. A dose reduction of L-OHP by 30%?50% may be advisable for the initial administration, given the need for careful administration of chemotherapy in HD patients, with particular attention to the development of hematological toxicities and neuropathy.     

A case of diaphragmatic hernia incarceration after a heart transplant operation

We report a case of a diaphragmatic hernia after a heart transplant operation. A 43-year-old woman, who underwent orthotropic heart transplantation for hypertrophic cadiomyopathy two year earlier, presented with vomiting and epigastric pain. A computed tomography scan showed that the stomach and transverse colon were dislocated in the left thoracic cavity. We diagnosed left diaphragmatic hernia incarceration and performed laparoscopic repair of the diaphragmatic hernia. A 12 × 8 cm diaphragmatic defect was found intraoperatively on the ventrolateral aspect of the left diaphragm, and the stomach with volvulus had herniated into the thorax through the defect. The hernia was considered to be iatrogenic. The diaphragmatic defect was large, and the diaphragm was thinning. We closed the defect by mesh repair. Laparoscopic mesh repair of the diaphragmatic hernia could be performed safely and with minimal invasiveness.     

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

Postoperative development of sarcopenia is a strong predictor of a poor prognosis in patients with adenocarcinoma of the esophagogastric junction and upper gastric cancer

Background

There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).

Shoulder and elbow pain in junior high school baseball players: Results of a nationwide survey

BackgroundDespite proposals and guidelines to prevent baseball injuries in young players by societies and organizations, many shoulder and elbow injuries continue to occur among junior high school baseball players. In order to investigate the training conditions of junior high school baseball players and the risk factors for shoulder and elbow pain in the players, we conducted a questionnaire survey among junior high school baseball players throughout the country.MethodsThe questionnaire survey was conducted among junior high school baseball players in September 2016.ResultsA total of 11,134 junior high school baseball players belonging to 495 teams responded to the survey. Among these, 4004 players trained every day of the week and 1151 players played baseball games every month with no off-season. Among 9752 players who did not have shoulder and/or elbow pain in the spring and summer of 2015, 19.2% of players experienced elbow pain over the course of one year, 13.6% of players experienced shoulder pain, and 28.0% complained of shoulder and/or elbow pain. The frequency of elbow pain was more than that of shoulder pain. At risk for shoulder pain were pitchers and catchers and second-year students, while risk factors for elbow pain were playing pitcher and catcher positions, pitching or throwing ≥300 balls per week, playing ≥10 games on average per month and being left-handed.ConclusionRisk factors for shoulder pain were different from those for elbow pain. To prevent elbow pain, coaches should pay attention to pitchers and catchers and left-handed players and not allow players to pitch or throw ≥300 full-power balls per week or participate in ≥10 games per month. They should also pay attention to pitchers and catchers and second-year students to prevent shoulder pain. It is important for coaches to train multiple pitchers and catchers.     

Japanese version of The Cancer Genome Atlas,JCGA, established using fresh frozen tumors obtained from 5143 cancer patients

This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single‐center study called “High‐tech Omics‐based Patient Evaluation” or “Project HOPE” conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole‐exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed “Shizuoka Multi‐omics Analysis Protocol” developed in‐house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non–cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients.     

No clear survival benefit of azacitidine for lower‐risk myelodysplastic syndromes: A retrospective study of Nagasaki

The efficacy of azacitidine (AZA) on survival of lower risk (LR) ‐ myelodysplastic syndromes (MDS) is controversial. To address this issue, we retrospectively evaluated the long‐term survival benefit of AZA for patients with LR‐MDS defined by International Prognostic Scoring System (IPSS). Using data from 489 patients with LR‐MDS in Nagasaki, hematologic responses according to International Working Group 2006 and overall survival (OS) were compared among patients that received best supportive care (BSC), immunosuppressive therapy (IST), erythropoiesis‐stimulating agents (ESA), and AZA. Patients treated with AZA showed complete remission (CR) rate at 11.3%, marrow CR at 1.9%, and any hematologic improvement at 34.0%, with transfusion independence (TI) of red blood cells in 27.3% of patients. and platelet in 20% of patients, respectively. Median OS for patients received IST, ESA, BSC, and AZA (not reached, 91 months, 58 months, and 29 months, respectively) differed significantly (P < .001). Infection‐related severe adverse events were observed in more than 20% of patients treated with AZA. Multivariate analysis showed age, sex, IPSS score at diagnosis, and transfusion dependence were significant for OS, but AZA treatment was not, which maintained even response to AZA, and IPSS risk status at AZA administration was added as factors. We could not find significant survival benefit of AZA treatment for LR‐MDS patients.