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. 相似文献
BACKGROUND Minimally invasive surgery for gastric cancer(GC) has gained widespread use as a safe curative procedure especially for early GC.AIM To determine risk factors for postoperative complications after minimally invasive gastrectomy for GC.METHODS Between January 2009 and June 2019, 1716 consecutive patients were referred to our division for primary GC. Among them, 1401 patients who were diagnosed with both clinical and pathological Stage Ⅲ or lower GC and underwent robotic gastrectomy(RG) or laparoscopic gastrectomy(LG) were enrolled. Retrospective chart review and multivariate analysis were performed for identifying risk factors for postoperative morbidity.RESULTS Morbidity following minimally invasive gastrectomy was observed in 7.5% of the patients. Multivariate analyses demonstrated that non-robotic minimally invasive surgery, male gender, and an operative time of ≥ 360 min were significant independent risk factors for morbidity. Therefore, morbidity was compared between RG and LG. Accordingly, propensity-matched cohort analysis revealed that the RG group had significantly fewer intra-abdominal infectious complications than the LG group(2.5% vs 5.9%, respectively; P = 0.038), while no significant differences were noted for other local or systemic complications.Multivariate analyses of the propensity-matched cohort revealed that non-robotic minimally invasive surgery [odds ratio = 2.463(1.070–5.682); P = 0.034] was a significant independent risk factor for intra-abdominal infectious complications.CONCLUSION The findings showed that robotic surgery might improve short-term outcomes following minimally invasive radical gastrectomy by reducing intra-abdominal infectious complications. 相似文献
Purpose: Small pulmonary lesions that include ground-glass attenuation have been increasingly discovered because of progressive imaging diagnostic technologies. Despite the detection of such small lesions, sometimes it is quite difficult to localize them because of their size or considerable depth from the visceral pleura. In the present study, we examined the usefulness of computed tomography-guided lipiodol marking for thoracoscopic resection of impalpable pulmonary nodules.Methods: Fifty-six patients with an undiagnosed peripheral lesion(s) of the lung who had undergone preoperative computed tomography-guided lipiodol marking followed by video-assisted thoracoscopic surgery were studied.Results: All of the nodules were successfully marked by computed tomography-guided lipiodol marking, and all except for one case were localized by means of intraoperative fluoroscopy as clear spots. With regard to complications, pneumothorax occurred in 21 patients (37.5%), and only one patient required transient drainage. Although hemorrhaging in the lung parenchyma and hemosputum occurred in nine patients (16.1%) and one patient (1.8%), respectively, no patients were in serious condition. No intra- or postoperative mortality or morbidity was observed.Conclusion: Preoperative computed tomography-guided lipiodol marking of small or impalpable pulmonary nodules is a safe and useful procedure for thoracoscopic resection of the lung. 相似文献
Purpose: Mouse double-stranded DNA-dependent protein kinase (DNA-PK) activity is heat sensitive. Recovery of heat-inactivated DNA repair activity is a problem after combination therapy with radiation and heat. We investigated the mechanism of recovery of heat-inactivated DNA-PK activity.
Methods: Hybrid cells containing a fragment of human chromosome 8 in scid cells (RD13B2) were used. DNA-PK activity was measured by an in vitro assay. Immunoprecipitation of the nuclear extract was performed with an anti-Ku80 antibody. Proteins co-precipitated with Ku80 were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and detected by Western blotting using anti-heat shock protein (HSP)72 and anti-heat shock cognate protein (HSC)73 antibodies. HSC73 was overexpressed with the pcDNA3.1 vector. Short hairpin (sh)RNA was used to downregulate HSC73 and HSP72.
Results: The activity of heat-inactivated DNA-PK recovered to about 50% of control during an additional incubation at 37?°C after heat treatment at 44?°C for 15?min in the presence of cycloheximide (which inhibits de novo protein synthesis). Maximal recovery was observed within 3?h of incubation at 37?°C after heat treatment. Constitutively expressed HSC73, which folds newly synthesized proteins, reached maximal levels 3?h after heat treatment using a co-immunoprecipitation assay with the Ku80 protein. Inhibiting HSC73, but not HSP72, expression with shRNA decreased the recovery of DNA-PK activity after heat treatment.
Conclusions: These results suggest that de novo protein synthesis is unnecessary for recovery of some heat-inactivated DNA-PK. Rather, it might be reactivated by the molecular chaperone activity of HSC73, but not HSP72. 相似文献
Sentinel lymph node biopsy (SLNB) is a widely accepted standard procedure for patients with clinically localized melanoma. Melanoma prevalence and Clark's subtype differ between Asians and Caucasians. Here, we evaluated our experience on SLNB for cutaneous melanoma in a Japanese population. SLNB was performed for patients with melanoma between July 2000 and June 2014. We retrospectively analyzed 102 patients regarding association of clinicopathological features with sentinel lymph node (SLN) status, melanoma‐specific survival (MSS) and disease‐free survival (DFS). A positive SLN was significantly associated with primary Breslow thickness. Compared with 43 patients with negative SLN, 59 patients with positive SLN had significantly shorter MSS (5‐year survival rate, 94.3% vs 63.2%; P =0.0002) and DFS (5‐year survival rate, 92.7% vs 63.4%; P =0.0004). According to our subgroup analyses, nine patients with positive non‐SLN had significantly shorter MSS compared with 32 patients with negative non‐SLN (5‐year survival rate, 32.4% vs 68.5%; P =0.0273). The survival of 51 Japanese patients with acral lentiginous melanoma (ALM) was not inferior to the survival of patients with other Clark's subtype. Breslow thickness is an important factor for both MSS and DFS, and the status of SLN is the most predictive prognostic factor in Japanese patients with clinically localized melanomas, as in case of Caucasians. Features of ALM may be different between Asians and Caucasians. 相似文献
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. 相似文献