Effect of seaweed feeding before calving on colostral IgA concentration in Japanese Black cows.

In this study, we investigated the effect of feeding seaweed to Japanese Black cows before calving on IgA concentrations in colostrum. Seven Japanese Black breeding cows were used as test animals, with three cows in the seaweed-fed group (seaweed group) and four in the seaweed-non-fed group (control group). Each cow was fed 6 kg of sudangrass hay and 2.5 kg of compound feed twice daily (09:00 a.m. and 04:00 p.m.) as basal diets. Both groups had free access to water. In the seaweed group, commercially available seaweed feed was fed from 2 months before calving until the day of calving. The seaweed of 150 g/head/day was added to the basal diet at the morning feeding. Colostrum collected immediately after calving was used to measure IgA concentrations by ELISA. The IgA concentration in colostrum was significantly higher in the seaweed group than in the control group (P < 0.05). This suggested that feeding seaweed to Japanese Black cows before calving may increase IgA concentration in colostrum.

A Prospective, Single-arm, Multicenter Trial of Diverting Stoma Followed by Neoadjuvant Chemotherapy Using mFOLFOX6 for Obstructive Colon Cancer: YCOG 1305 (PROBE Study).

OBJECTIVE: We conducted the first prospective clinical trial of neoadjuvant chemotherapy for patients with obstructive colon cancer. BACKGROUND: Obstructive colorectal cancer is locally advanced colorectal cancer with a poor prognosis. The effect of neoadjuvant chemotherapy for obstructive colon cancer is unclear. METHODS: We conducted a single arm, multicenter trial involving patients from the Yokohama Clinical Oncology Group with obstructive colon cancer. All eligible patients underwent diverting stoma formation before neoadjuvant chemotherapy. Patient received 6 cycles of mFOLFOX6 followed by primary tumor surgery and then 6 cycles of adjuvant chemotherapy. The primary endpoint was the objective response rate of all intended neoadjuvant therapy. The study was registered with the Japanese Clinical Trials Registry as UMIN000013198. RESULTS: Between April 2014, and July 2016, 50 patients were registered, and 46 received neoadjuvant chemotherapy. The objective response rate as the primary endpoint was 67.4%. The most common grade >3 adverse event associated with neoadjuvant chemotherapy was neutropenia (28.3%). Forty-five patients underwent surgical resection of the primary lesion (R0 resection in all cases). Grade >2 surgery-related complications occurred in 7 patients (15.6%). The downstaging rate was 48.9%, and the moderate or greater regression rate was 52.2%; no cases showed pathological complete response. Adjuvant chemotherapy with mFOLFOX6 was performed in 34 patients (75.6%). The 3-year relapse-free and overall survival rates were 76.5% and 95.4%, respectively. CONCLUSION: Neoadjuvant chemotherapy using mFOLFOX6 was feasible and might be a treatment option for patients with obstructive colon cancer. Further large-scale studies are warranted to confirm the present findings.

Effect of Postoperative Coffee Consumption on Postoperative Ileus after Abdominal Surgery: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Previous systematic reviews have not clarified the effect of postoperative coffee consumption on the incidence of postoperative ileus (POI) and the length of hospital stay (LOS). We aimed to assess its effect on these postoperative outcomes. METHODS: Studies evaluating postoperative coffee consumption were searched using electronic databases until September 2021 to perform random-effect meta-analysis. The quality of evidence was assessed using the Cochrane risk-of-bias tool. Caffeinated and decaffeinated coffee were also compared. RESULTS: Thirteen trials (1246 patients) and nine ongoing trials were included. Of the 13 trials, 6 were on colorectal surgery, 5 on caesarean section, and 2 on gynecological surgery. Coffee reduced the time to first defecation (mean difference (MD) -10.1 min; 95% confidence interval (CI) = -14.5 to -5.6), POI (risk ratio 0.42; 95% CI = 0.26 to 0.69); and LOS (MD -1.5; 95% CI = -2.7 to -0.3). This trend was similar in colorectal and gynecological surgeries. Coffee had no adverse effects. There was no difference in POI or LOS between caffeinated and decaffeinated coffee (p > 0.05). The certainty of evidence was low to moderate. CONCLUSION: This review showed that postoperative coffee consumption, regardless of caffeine content, likely reduces POI and LOS after colorectal and gynecological surgery.

Lidocaine spray versus viscous lidocaine solution for pharyngeal local anesthesia in upper gastrointestinal endoscopy: Systematic review and meta-analysis.

OBJECTIVES: There are two major methods for local anesthesia by lidocaine before upper gastrointestinal endoscopy: simple spray and viscous solution. We aimed to assess the efficacy and safety by meta-analysis between these two methods. METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases through October 2019 to perform meta-analyses using random-effects models. The primary outcomes were participants' pain/discomfort, satisfaction, and anaphylactic shock. Three reviewers independently searched for articles, extracted data, and assessed the risk of bias. We evaluated the certainty of evidence based on the Grading of Recommendations, Assessment, Development, and Evaluation approach. This study was registered in PROSPERO (CRD42020155611). RESULTS: We included seven randomized controlled trials (2667 participants). The participants' pain/discomfort may be similar between the lidocaine spray and viscous solution [standardized mean difference 0.03, 95% confidence intervals (CI) -0.37 to 0.42; I2  = 93%; low certainty of evidence]. The lidocaine spray probably increased participants' satisfaction compared with the viscous solution (relative risk 1.22; 95% CI, 1.02 to 1.47; I2  = 47%; moderate certainty of evidence). No anaphylactic shock occurred in four studies (low certainty of evidence). Four studies had high risks of selection bias. CONCLUSION: The use of lidocaine spray for local anesthesia provided better satisfaction scores than the viscous solution, and both methods have the same effect with regards to the control of discomfort and pain. Further studies in large multicenter randomized controlled trials with a pre-registration protocol are needed.

A prospective, single-arm, multicenter trial of neoadjuvant chemotherapy with mFOLFOX6 plus panitumumab without radiotherapy for locally advanced rectal cancer.

PURPOSE: The present study evaluated the safety and efficacy of neoadjuvant chemotherapy with modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus panitumumab in clinical stage III rectal cancer with KRAS wild-type. METHODS: We conducted a prospective multicenter phase II trial. KRAS wild-type clinical stage III rectal cancer patients were enrolled. Patients received 6 cycles of mFOLFOX6 with 6 mg/kg panitumumab as neoadjuvant chemotherapy. The primary outcome was the response rate (RR) defined by RECIST. Lateral lymph node dissection (LLDN) was performed when patients had a locally advanced tumor < 9 cm from the anal margin. RESULTS: A total of 50 patients were enrolled. Twelve (24.0%) experienced grade 3-4 adverse events during neoadjuvant chemotherapy. The RR was 88.0% (complete response 2.0%, partial response 86.0%), which met the primary outcome. All patients underwent laparoscopic surgery and achieved R0 resection. Seven patients underwent resection of other adjacent organs, and 43 underwent LLND. Twelve patients (24.0%) experienced grade 3-4 postoperative complications, and 4 (8.0%) had pathological complete response (pCR). Thirteen patients (26.0%) had lymph node metastasis. Forty-five patients (90.0%) received postoperative adjuvant chemotherapy. The 3-year relapse-free survival (RFS) and overall survival (OS) rates were 79.0% and 93.7%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy of mFOLFOX6 plus panitumumab without radiotherapy resulted in a low pCR rate but a high PR rate, low local recurrence rate, and good long-term outcome, suggesting that this treatment strategy may be a viable option for patients unable or unwilling to receive radiotherapy. The trial was registered with the UMIN Clinical Trials Registry, number 000006039.

The effect of TJ-28 (Eppikajutsuto) on the prevention of hand-foot syndrome using Capecitabine for colorectal cancer: The Yokohama Clinical Oncology Group Study (YCOG1102).

BACKGROUND: Eppikajututo (TJ-28, a Kampo medicine) is effective against rheumatoid arthritis and eczema. We conducted a randomized comparative trial to assess the efficacy of TJ-28 for preventing hand-foot syndrome (HFS) as a complication of adjuvant chemotherapy using capecitabine. METHODS: The present study was a multi-institutional randomized-controlled trial (UMIN000005899). Colorectal cancer patients scheduled to receive capecitabine chemotherapy as adjuvant therapy were randomly assigned to receive TJ-28 (7500 mg/day) or oral pyridoxine (60 mg/day). Patients were monitored for the development of grade ≥ 2 HFS according to the National Cancer Institute Common Toxicity Criteria until chemotherapy completion. RESULTS: Twenty-two patients were enrolled in this study. The relative dose intensity of capecitabine was 76.2% in the TJ-28 group and 68.2% in the pyridoxine group. Grade ≥ 2 HFS developed in 6 (50.0%) of 12 TJ-28 patients and in 4 (40.0%) of 10 pyridoxine patients. Chemotherapy treatment failure was observed in seven patients, mainly due to HFS, liver dysfunction, diarrhea, and neutropenia. Chemotherapy treatment failure due to HFS occurred in none of the TJ-28 group and 2 patients (20.0%) in the pyridoxine group (p = 0.114). CONCLUSION: Capecitabine-associated HFS was not markedly prevented by TJ-28 compared with pyridoxine. However, TJ-28 might support the continuation of chemotherapy with capecitabine. Further studies are warranted to clarify the benefits of TJ-28.

Supplemental feeding of a gut microbial metabolite of linoleic acid, 10-hydroxy-cis-12-octadecenoic acid, alleviates spontaneous atopic dermatitis and modulates intestinal microbiota in NC/nga mice.

The present study investigated the antiallergic and anti-inflammatory effects of 10-hydroxy-cis-12-octadecenoic acid (HYA), a novel gut microbial metabolite of linoleic acid, in NC/Nga mice, a model of atopic dermatitis (AD). Feeding HYA decreased the plasma immunoglobulin E level and skin infiltration of mast cells with a concomitant decrease in dermatitis score. HYA feeding decreased TNF-α and increased claudin-1, a tight junction protein, levels in the mouse skin. Cytokine expression levels in the skin and intestinal Peyer's patches cells suggested that HYA improved the Th1/Th2 balance in mice. Immunoglobulin A concentration in the feces of the HYA-fed mice was approximately four times higher than that in the control mice. Finally, denaturing gradient gel electrophoresis of the PCR-amplified 16 S rRNA gene of fecal microbes indicated the modification of microbiota by HYA. Taken together, the alterations in the intestinal microbiota might be, at least in part, associated with the antiallergic effect of HYA.

Phytoestrogenic activity of blackcurrant (Ribes nigrum) anthocyanins is mediated through estrogen receptor alpha.

SCOPE: Blackcurrants (Ribes nigrum L., Grossulariaceae) contain high amounts of anthocyanin polyphenols, which have antioxidant and anti-carcinogenic health benefits. This study analyzed the potential phytoestrogenic effects of blackcurrant extract (BCE) in breast cancer (MCF-7) and human endometrial cancer (Ishikawa) cell lines that over-express estrogen receptor alpha (ERα), as well as in immature female rats. METHODS AND RESULTS: Microarray analysis and Ingenuity® Pathway Analysis showed that BCE activated the ERα pathway, whereas quantitative-PCR confirmed that BCE and four types of anthocyanins up-regulated genes downstream of ERα. BCE (0.1-1.0 µg/mL) and anthocyanins (0.1-10 µM) induced MCF-7 cell proliferation; however, this effect was blocked by ER antagonist fulvestrant. Flow cytometry showed that anthocyanins reduced and increased the number of MCF-7 cells in the G0/G1 and G2/M phases, respectively. Anthocyanins stimulated ERα transcriptional activity in human ERα reporter assays and induced alkaline phosphatase activity in Ishikawa cells. Competition assays and in silico analysis indicated that anthocyanins bind to ERα. Finally, BCE focally induced stratification of columnar epithelial cells in the rat uterus and increased cytoplasmic mucin levels in these cells. CONCLUSION: These results suggest that blackcurrant anthocyanins act as phytoestrogens in vitro and in vivo.

Simultaneous determination of water-soluble vitamins in beverages and dietary supplements by LC-MS/MS.

An LC-MS/MS method was developed for the simultaneous determination of 15 water-soluble vitamins that are widely used as additives in beverages and dietary supplements. This combined method involves the following simple pre-treatment procedures: dietary supplement samples were prepared by centrifugation and filtration after an extraction step, whereas beverage samples were diluted prior to injection. Chromatographic analysis in this method utilised a multi-mode ODS column, which provided reverse-phase, anion- and cation-exchange capacities, and therefore improved the retention of highly polar analytes such as water-soluble vitamins. Additionally, the multi-mode ODS column did not require adding ion pair reagents to the mobile phase. We optimised the chromatographic separation of 15 water-soluble vitamins by adjusting the mobile phase pH and the organic solvent. We also conducted an analysis of a NIST Standard Reference Material (SRM 3280 Multi-vitamin/Multi-element tablets) using this method to verify its accuracy. In addition, the method was applied to identify the vitamins in commercial beverages and dietary supplements. By comparing results with the label values and results obtained by official methods, it was concluded that the method could be used for quality control and to compose nutrition labels for vitamin-enriched products.

Extraction efficiency of hydrophilic and lipophilic antioxidants from lyophilized foods using pressurized liquid extraction and manual extraction.

The efficient extraction of antioxidants from food samples is necessary in order to accurately measure their antioxidant capacities. α-Tocopherol and gallic acid were spiked into samples of 5 lyophilized and pulverized vegetables and fruits (onion, cabbage, Satsuma mandarin orange, pumpkin, and spinach). The lipophilic and hydrophilic antioxidants in the samples were sequentially extracted with a mixed solvent of n-hexane and dichloromethane, and then with acetic acid-acidified aqueous methanol. Duplicate samples were extracted: one set was extracted using an automated pressurized liquid extraction apparatus, and the other set was extracted manually. Spiked α-tocopherol and gallic acid were recovered almost quantitatively in the extracted lipophilic and hydrophilic fractions, respectively, especially when pressurized liquid extraction was used. The expected increase in lipophilic oxygen radical absorbance capacity (L-ORAC) due to spiking with α-tocopherol, and the expected increase in 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities and total polyphenol content due to spiking with gallic acid, were all recovered in high yield. Relatively low recoveries, as reflected in the hydrophilic ORAC (H-ORAC) value, were obtained following spiking with gallic acid, suggesting an interaction between gallic acid and endogenous antioxidants. The H-ORAC values of gallic acid-spiked samples were almost the same as those of postadded (spiked) samples. These results clearly indicate that lipophilic and hydrophilic antioxidants are effectively extracted from lyophilized food, especially when pressurized liquid extraction is used.

Comparison of scavenging capacities of vegetables by ORAC and EPR.

Reactive oxygen species (ROS) are considered to be causative agents of many health problems. In spite of this, the radical-specific scavenging capacities of food samples have not been well studied. In the present work, we have developed an electron paramagnetic resonance (EPR) spin trapping method for analysis of the scavenging capacities of food samples for multiple ROS, utilising the same photolysis procedure for generating each type of radical. The optimal conditions for effective evaluation of hydroxyl, superoxide, and alkoxyl radical scavenging capacity were determined. Quantification of radical adducts was found to be highly reproducible, with variations of less than 4%. The optimised EPR spin trapping method was used to analyse the scavenging capacities of 54 different vegetable extracts for multiple radicals, and the results were compared with oxygen radical absorption capacity values. Good correlations between the two methods were observed for superoxide and alkoxyl radicals, but not for hydroxyl.

The Effect of Pyridoxine for Prevention of Hand-Foot Syndrome in Colorectal Cancer Patients with Adjuvant Chemotherapy Using Capecitabine: A Randomized Study.

UNLABELLED: BACKGROUND/Aims: To determine the effect of the pyridoxine for prevention of hand-foot syndrome in colorectal cancer patients with adjuvant chemotherapy using capecitabine. METHODOLOGY: Colorectal cancer patients scheduled for capecitabine chemotherapy as adjuvant setting were randomly assigned to with or without concurrent oral pyridoxine (60 mg/d) groups. Patients were monitored whether being a development of National Cancer Institute Common Toxicity Criteria grade 2 or worse HFS until chemotherapy ended. RESULTS: Sixty patients were enrolled in this study. Relative dose intensity was 89.5% in total. The median number of chemotherapy cycles to grade 2 or worse HFS was four in both groups. Grade 2 or worse HES developed in 18 (60.0%) of 30 control patients and in 18 (60.0%) of 30 pyridoxine patients. The cumulative dose of capecitabine to grade 2 or worse HFS was not different between the two groups. CONCLUSIONS: Pyridoxine is not effective in prevention of capecitabine-associated HFS.

[A case of consciousness disorder induced by the syndrome of inappropriate secretion of antidiuretic hormone following cisplatin and 5-fluorouracil chemotherapy in a patient with esophageal cancer].

We report a case of consciousness disorder following the fourth course of chemotherapy with cisplatin (CDDP) and 5- fluorouracil (5-FU) in a patient with esophageal cancer. A 74-year-old man was admitted to our hospital to receive chemotherapy for esophageal cancer. Six days after chemotherapy, the patient showed impaired consciousness and his serum sodium concentration was found to be 125 mEq/L, but no edema or dehydration was noted. This hyponatremic state was diagnosed as CDDP-induced syndrome of inappropriate secretion of antidiuretic hormone (SIADH) on the basis of serum and urine hypo-osmolality. Accordingly, fluid intake was restricted and sodium supplements were administered, resulting in an appropriate increase in the serum sodium concentration to 132 mEq/L in 4 days.

Evaluation of a method to quantify quercetin aglycone in onion (Allium cepa) by single- and multi-laboratory validation studies.

Official Methods of Analysis of AOAC International (OMA) 2006.07 was originally designed for quantifying flavonol aglycones in ginkgo dietary supplements. To determine whether the method is applicable to the quantification of flavonol aglycones in lyophilized onion samples, single- and multi-laboratory validation studies were performed. Triplicated measurements on 3 different days revealed that the mean quercetin content was 3.48 g/kg dry weight, and the relative repeatability standard deviation (RSD(r)) and the relative intermediate standard deviation (RSD(int)) were 0.8 and 1.8%, respectively. The recovery of quercetin-3-O-glucoside spiked at 3 different amounts (1.56, 3.12, and 6.24 g/kg dry weight of onion) ranged from 98.42 to 100.31%, and the RSD(r) and RSD(int) ranged from 2.2 to 5.9%, and from 3.4 to 5.2%, respectively. A multi-laboratory validation study showed that the mean quercetin contents were 2.80 and 6.61 g/kg dry weight, and that satisfactory inter-laboratory precision (RSD(r) and RSD(R) ranged from 0.41 to 0.92%, and from 6.73 to 7.62%, respectively); all HorRat values were less than 2. These results indicate that OMA 2006.07 is applicable to the determination of the quercetin content of lyophilized onion samples.

2,4-Dinitrofluorobenzene-induced contact hypersensitivity response in NC/Nga mice fed fructo-oligosaccharide.

Strategies to manipulate gut microbiota in infancy have been considered to prevent the development of allergic diseases later in life. We previously demonstrated that maternal dietary supplementation with fructo-oligosaccharide (FOS) during pregnancy and lactation modulated the composition of gut microbiota and diminished the severity of spontaneously developing atopic dermatitis-like skin lesions in the offspring of NC/Nga mice. The present study tested whether dietary FOS affects contact hypersensitivity (CHS), another model for allergic skin disease, in NC/Nga mice. In experiment 1, 5-wk-old female NC/Nga mice were fed diets either with or without FOS supplementation for 3 wk and then received 2,4-dinitrofluorobenzene (DNFB) on the ear auricle 5 times at 7-d intervals. FOS supplementation reduced CHS response as demonstrated by ear swelling. Quantitative RT-PCR analysis showed that mRNA levels for interleukin (IL)-10, IL-12p40, and IL-17 in the lesional ear skin were significantly lower in mice fed FOS. In experiment 2, female NC/Nga mice were fed diets either with or without FOS during pregnancy and lactation. After weaning, offspring were fed the diets supplemented with or without FOS. Three weeks after weaning, offspring received DNFB on the ear auricle 4 times at 7-d intervals. Although FOS supplementation after weaning reduced ear swelling, maternal FOS consumption was ineffective in offspring. The present data suggest that dietary FOS reduces CHS while maternal FOS consumption is ineffective in offspring of DNFB-treated NC/Nga mice.

Effects of fructo-oligosaccharide on DSS-induced colitis differ in mice fed nonpurified and purified diets.

We investigated whether feeding a purified compared with nonpurified diet supplemented with or without fructo-oligosaccharide (FOS; 50 g/kg diet) altered the response of C57BL/6 mice to DSS-induced diarrhea. In Expt. 1, we examined disease severity in mice receiving DSS (2% in drinking water) for 5 d. In Expt. 2, we measured cecal organic acid concentrations and fecal water-holding capacity (WHC). In Expts. 3 and 4, we tested whether polycarbophil calcium (PC), a water-absorbing polymer, altered fecal WHC and disease severity. FOS exacerbated diarrhea and weight loss in mice fed the purified diet and reduced fecal bleeding in mice fed the nonpurified diet (P < 0.05). Without DSS administration, cecal acetate and butyrate concentrations were higher in mice fed the nonpurified diet than in mice fed the purified diet (P < 0.05). Fecal WHC was higher in mice fed the nonpurified diet than in mice fed the purified diet (P < 0.05). One day after starting DSS administration, cecal succinate concentrations were higher in mice fed the FOS-supplemented purified diet than in mice fed the other 3 diets, whereas SCFA concentrations were higher in mice fed the nonpurified diet than in mice fed the purified diet (P < 0.05). PC supplementation increased fecal WHC and prevented FOS exacerbation of diarrhea in mice fed the purified diet (P < 0.05). We conclude that the effects of FOS on DSS-induced diarrhea differ in mice fed the purified and nonpurified diets. The protective effect of nonpurified diet was associated with increased production of organic acids and WHC in the intestinal contents.

Evaluation of narrow-band imaging as a complementary method for the detection of bladder cancer.

PURPOSE: We evaluated the use of narrow-band imaging (NBI) cystoscopy for the detection of bladder cancer and analyzed its diagnostic efficacy in cases of carcinoma in situ (CIS) and in cases with known urine cytology results. PATIENTS AND METHODS: A prospective controlled study of NBI was conducted in 104 consecutive patients with definite or suspected bladder cancer. Transurethral targeted biopsies were performed after white light imaging (WLI) and NBI cystoscopy, and the histologic outcomes were compared. RESULTS: A total of 313 biopsies were taken, including 161 from sites identified as potentially abnormal by NBI and/or WLI cystoscopy, and 152 from apparently normal sites. The percentage of malignancies in the sites identified only by NBI was 55.7% (39/70 places). In 26.9% of patients (28/104), bladder tumors were detected only by NBI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio of a negative test (NLR) for the detection of bladder tumors using NBI in all patients were 92.7%, 70.9%, 63.4%, 94.7%, and 0.10, respectively. The sensitivity, specificity, PPV, NPV, and NLR for the detection of CIS using NBI were 89.7%, 74.5%, 78.8%, 87.2%, and 0.14, respectively. The sensitivity, specificity, PPV, NPV, and NLR for the detection of bladder tumors using NBI in patients with positive vs negative urine cytology were 85.4% vs 98.4%, 75.7% vs 66.3%, 61.2% vs 64.5%, 92.0% vs 98.5%, and 0.19 vs 0.02, respectively. CONCLUSIONS: NBI is a simple and effective method for identifying bladder tumors including CIS without the need for dyes because of its high sensitivity, high NPV, and low NLR.

Tolerable sorafenib therapy for a renal cell carcinoma patient with hemodialysis: a case study.

Sorafenib (Nexavar(®)) has been approved for the treatment of advanced renal cell carcinoma (RCC) and hepatocellular carcinoma. There is little information on the dosage adjustment of sorafenib for patients with end-stage renal failure. Herein, we have examined the effect of hemodialysis on the pharmacokinetics of sorafenib and its major active metabolite, M-2, and assessed sorafenib-related toxicity throughout the therapy. The patient was a 54-year-old man who was diagnosed with advanced RCC. Pharmacokinetic analysis was carried out on days 9 and 183. The patient had stable disease on day 77 and showed progression on day 181. He has received about 6 months of continuous treatment with sorafenib 800 mg/day without any clinically relevant toxicity. The pharmacokinetic parameters of sorafenib such as C (max) and AUC(0-12) on day 183 were in the range of the reference values reported in patients with normal renal function. Our results suggest that sorafenib administered at a dose of 400 mg twice per day was well tolerated, at least for 6 months, for a patient undergoing hemodialysis.