An integrated analysis of hyponatremia in cancer patients receiving platinum-based or nonplatinum-based chemotherapy in clinical trials (JCOG1405-A)

Background: Hyponatremia is a common electrolyte abnormality in cancer patients who receive chemotherapy. Among anticancer agents, platinum-based agents are reported to cause chemotherapy-induced hyponatremia. However, the actual incidence and risk factors remain unknown. Results: The reports of 29 trials were analyzed. The incidence of grade 3/4 hyponatremia was 11.9% in patients treated with platinum-based chemotherapy and 3.8% in those treated with nonplatinum-based regimens (P < 0.01). Univariable analysis revealed a high incidence of hyponatremia in patients receiving cisplatin, three-drug combination regimen, two-drug combination regimen with amrubicin or irinotecan, or high-dose cisplatin (weekly equivalent cisplatin dose ≥20 mg/m²), and in patients with small-cell lung cancer. Conclusion: This is the first report of the actual incidence and the potential risk factors of chemotherapy-induced hyponatremia. Careful monitoring of serum sodium level is needed when platinum-based chemotherapy is administered. Methods: This study included all clinical trials of systemic chemotherapies for solid cancers that were conducted by the Japan Clinical Oncology Group (JCOG) after January 2000 and of which the patient enrolment was completed by January 2014. The latest reports of each trial were used for analysis. The incidence of chemotherapy-induced grade 3/4 hyponatremia and the potential risk factors were investigated with univariable analysis

Impact of neoadjuvant chemotherapy on physical fitness, physical activity, and health-related quality of life of patients with resectable esophageal cancer.

Neoadjuvant chemotherapy (NAC) followed by radical surgery is the standard treatment for patients with resectable esophageal squamous cell carcinoma (ESCC) in Japan. However, some adverse events associated with NAC may result in a decrease in physical fitness that may influence the patient's ability to tolerate surgery. The purpose of this study was to evaluate the impact of NAC on physical fitness, physical activity, and health-related quality of life (HRQOL) of patients with ESCC

Tissue damage in the canine normal esophagus by photoactivation with talaporfin sodium (laserphyrin): a preclinical study.

[Background] Treatment failure at the primary site after chemoradiotherapy is a major problem in achieving a complete response. Photodynamic therapy (PDT) with porfimer sodium (Photofrin®) has some problems such as the requirement for shielding from light for several weeks and a high incidence of skin phototoxicity. PDT with talaporfin sodium (Laserphyrin) is less toxic and is expected to have a better effect compared with Photofrin PDT. However, Laserphyrin PDT is not approved for use in the esophagus. In this preclinical study, we investigated tissue damage of the canine normal esophagus caused by photoactivation with Laserphyrin. [Methodology/Principal Findings] Diode laser irradiation was performed at 60 min after administration. An area 5 cm oral to the esophagogastric junction was irradiated at 25 J/cm2, 50 J/cm2, and 100 J/cm2 using a three-step escalation. The irradiated areas were evaluated endoscopically on postirradiation days 1 and 7, and were subjected to histological examination after autopsy. The areas injured by photoactivation were 52 mm2, 498 mm2, and 831 mm2 after irradiation at 25 J/cm2, 50 J/cm2, and 100 J/cm2, respectively. Tissue injury was observed in the muscle layer or even deeper at any irradiation level and became more severe as the irradiation dose increased. At 100 J/cm2 both inflammatory changes and necrosis were seen histologically in extra-adventitial tissue. [Conclusions/Significance]To minimize injury of the normal esophagus by photoactivation with Laserphyrin, diode laser irradiation at 25 J/cm2 appears to be safe. For human application, it would be desirable to investigate the optimal laser dose starting from this level

Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study

[Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676

胃小陥凹性病変の良悪性鑑別診断における狭帯域光拡大内視鏡観察と白色光拡大内視鏡観察の診断能を比較する前向き試験

京都大学0048新制・論文博士博士(医学)乙第12560号論医博第2026号新制||医||988(附属図書館)28904(主査)教授 坂井 義治, 教授 羽賀 博典, 教授 富樫 かおり学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDA

The changing patterns of dispensing branded and generic drugs for the treatment of gastroesophageal reflux disease between 2006 and 2011 in Japan: A retrospective cohort study

[Background]Despite rising healthcare costs, generic drugs are less frequently dispensed in Japan compared with other developed countries. This study aimed to describe changes in dispensing of branded and generic drugs and to explore possible factors that promote the use of generic drugs. [Methods]We conducted a retrospective cohort study using a Japanese medical and pharmacy claims database. All proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs) with indications for gastroesophageal reflux disease (GERD) described on Japanese labels were included. Patterns of dispensing branded and generic drugs for the treatment of GERD between 2006 and 2011 were analyzed. Multivariate logistic regression was applied to investigate factors associated with receiving generic drugs. [Results]The study cohort included 14, 590 patients (male: 50.2%, mean age: 43.1 years). Branded drugs for GERD were still frequently dispensed despite an increase in the share of generic drugs. Only 4.3% of patients who initially received branded drugs switched to generic drugs. The percentage of patients who received only generic drugs increased over time (6.5% to 22.1%). The frequency of generic drug dispensing was the highest in the setting where both prescription and dispensing were implemented in clinics (43.3%), while the lowest in the setting where both prescription and dispensing were implemented in hospitals (11.5%). Factors associated with receiving generic drugs included year of dispensing (adjusted OR 2.22, 95% CI 1.94 to 2.55 for 2009–11 v 2006–8), prescription and dispensing setting (OR 1.81, 95% CI 1.44 to 2.26 for prescription in hospitals and dispensing in community pharmacies; OR 2.21, 95% CI 1.80 to 2.72 for prescription in clinics and dispensing in community pharmacies; and OR 4.55, 95% CI 3.68 to 5.62 for prescription and dispensing in clinics v prescription and dispensing in hospitals) and H2RAs (OR 1.64, 95% CI 1.49 to 1.81 compared to PPIs). [Conclusions]The share of generic drugs for the treatment of GERD increased over time although branded drugs for GERD were still dispensed frequently. The use of generic drugs for GERD was influenced not only by government policies but also by changes in treatment approach and the setting of prescription and dispensing

Narrow-band imaging for the head and neck region and the upper gastrointestinal tract.

Endoscopy is essential for the diagnosis and treatment of cancers derived from the gastrointestinal tract. However, a conventional white-light image has technical limitations in detecting small or superficial lesions. Narrow-band imaging, especially with magnification, allows visualization of microstructure patterns and microvascular patterns on the mucosal surface. These technical breakthroughs enable endoscopists to easily detect small pre-neoplastic and neoplastic lesions and to make a differential diagnosis of these lesions. Appropriate diagnosis with narrow-band imaging contributes to minimally invasive endoscopic resection