Pharmacokinetic study of the oral fluorouracil antitumor agent S‐1 in patients with impaired renal function

Although dose reduction of S‐1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5‐fluorouracil, 5‐chloro‐2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S‐1 in patients with renal impairment. We classified patients receiving S‐1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S‐1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m²), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m²), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m²), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m²). Those in cohorts 3 and 4 treated with an adjusted dose of S‐1 showed a similar area under the curve for 5‐fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S‐1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S‐1 in patients with impaired renal function using eGFR is appropriate and safe.     

Sonodynamic Therapy: Advances and Challenges in Clinical Translation

Sonodynamic therapy (SDT) consists of the synergetic interaction between ultrasound and a chemical agent. In SDT, the cytotoxicity is triggered by ultrasonic stimuli, notably through cavitation. The unique features of SDT are relevant in the clinical context more than ever: the need for efficacy, accuracy, and safety while being noninvasive and preserving the patient's quality of life. However, despite the promising results of this technique, only a few clinical reports describe the use of SDT. The objective of this article is to provide an extensive overview of the clinical and preclinical research conducted in vivo on SDT, to identify the limitations, and to detail the developed strategies to overcome them.     

Coronary Artery Lumen Segmentation Using Location–Adaptive Threshold in Coronary Computed Tomographic Angiography: A Proof-of-Concept

ObjectiveTo compare the lumen parameters measured by the location-adaptive threshold method (LATM), in which the inter- and intra-scan attenuation variabilities of coronary computed tomographic angiography (CCTA) were corrected, and the scan-adaptive threshold method (SATM), in which only the inter-scan variability was corrected, with the reference standard measurement by intravascular ultrasonography (IVUS).Materials and MethodsThe Hounsfield unit (HU) values of whole voxels and the centerline in each of the cross-sections of the 22 target coronary artery segments were obtained from 15 patients between March 2009 and June 2010, in addition to the corresponding voxel size. Lumen volume was calculated mathematically as the voxel volume multiplied by the number of voxels with HU within a given range, defined as the lumen for each method, and compared with the IVUS-derived reference standard. Subgroup analysis of the lumen area was performed to investigate the effect of lumen size on the studied methods. Bland-Altman plots were used to evaluate the agreement between the measurements.ResultsLumen volumes measured by SATM was significantly smaller than that measured by IVUS (mean difference, 14.6 mm³; 95% confidence interval [CI], 4.9–24.3 mm³); the lumen volumes measured by LATM and IVUS were not significantly different (mean difference, −0.7 mm³; 95% CI, −9.1–7.7 mm³). The lumen area measured by SATM was significantly smaller than that measured by LATM in the smaller lumen area group (mean of difference, 1.07 mm²; 95% CI, 0.89–1.25 mm²) but not in the larger lumen area group (mean of difference, −0.07 mm²; 95% CI, −0.22–0.08 mm²). In the smaller lumen group, the mean difference was lower in the Bland-Altman plot of IVUS and LATM (0.46 mm²; 95% CI, 0.27–0.65 mm²) than in that of IVUS and SATM (1.53 mm²; 95% CI, 1.27–1.79 mm²).ConclusionSATM underestimated the lumen parameters for computed lumen segmentation in CCTA, and this may be overcome by using LATM.     

Idiopathic myointimal hyperplasia of mesenteric veins: Rare case of ischemic colitis mimicking inflammatory bowel disease

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood ischemic colitis that occurs in the rectosigmoid colon of predominantly young, previously healthy, male patients. A 76‐year‐old Japanese man presented to our hospital with a 1‐year history of worsening diarrhea, lower abdominal pain, and weight loss (−6 kg). Laboratory evaluation revealed white blood cell count of 13 200/μL, C‐reactive protein level of 2.0 mg/dL (normal range, 0.0–0.3), and negative results for stool culture (including Clostridium difficile). Colonoscopy showed circumferential and edematous narrowing of the sigmoid colon with deep longitude ulceration. Biopsy was done and examination of the specimen demonstrated no specific ischemia. The patient was treated with bowel rest, antibiotics, and i.v. fluids; however, his symptoms worsened. Finally, sigmoidectomy was carried out. Histological examination demonstrated significant myointimal hyperplasia of mesenteric veins leading to thickening and stenosis of the venous lumen. Therefore, the final diagnosis was IMHMV. Three months following sigmoidectomy, he was asymptomatic.     

Is Atrial Fibrillation a Risk Factor for Gastroesophageal Reflux Disease Occurrence?

Recent studies have reported an association between gastroesophageal reflux disease (GERD) and atrial fibrillation (AF). The objective of the present study was to evaluate whether AF is one of the risk factors for GERD occurrence.In this hospital-based, retrospective, case–control study, the patients were classified into 2 groups. The patients diagnosed with new AF were assigned to the AF group (n = 1612); those diagnosed without AF and GERD were assigned to the control group (n = 1612). The subjects in the control group were selected from outpatients of total healthcare center without a history of AF or GERD, and matched for age and gender. We evaluated the incidence of GERD and risk factors for GERD occurrence between the 2 groups.The number of patients experiencing occurrence of GERD during the follow-up period was significantly higher in the AF group than those in the control group, respectively (129 patients vs 98 subjects, P = 0.037). The incidence of GERD was significantly higher in the AF group than in the control group by Kaplan–Meier analysis with log-rank test (P = 0.008). The AF group''s adjusted hazard ratio of GERD occurrence against that of the control group was 1.37 (95% confidence interval [CI]: 1.16–1.57; P = 0.009) according to Cox''s proportional hazard model.The presence of AF appears to increase the incidence of GERD and may be considered a risk factor for the development of GERD. Further, large prospective and cohort studies will be required to better establish the correlation of GERD with AF.