Outcome of maintenance systemic chemotherapy with drug-free interval for metastatic urothelial carcinoma.

OBJECTIVE: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). METHODS: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. RESULTS: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. CONCLUSIONS: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

Dual Gas Treatment With Hydrogen and Carbon Monoxide Attenuates Oxidative Stress and Protects From Renal Ischemia-Reperfusion Injury.

BACKGROUND: Hydrogen (H2) and carbon monoxide (CO) gas are both reported to reduce reactive oxygen species and alleviate tissue ischemia-reperfusion (I-R) injury. The present study was conducted to evaluate the effects of a mixture of H2 gas and CO gas (dual gas) in comparison with hydrogen gas (H2: 2%) alone on I-R renal injury (composition of dual gas; N2: 77.8%; O2: 20.9%; H2: 1.30%; CO: 250 parts per million). METHODS: Adult male Sprague-Dawley rats (body weight 250-280 g) were divided into 5 groups: (1) sham operation control, (2) dual gas inhalation (dual treatment) without I-R treatment, (3) I-R renal injury, (4) H2 gas alone inhalation (H2 treatment) with I-R renal injury, and (5) dual treatment with I-R renal injury. I-R renal injury was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion, and then contralateral nephrectomy was performed 2 weeks later. Renal function was markedly decreased at 24 hours after reperfusion, and thereafter the effects of dual gas were assessed by histologic examination and determination of the superoxide radical, together with functional and molecular analyses. RESULTS: Pathologic examination of the kidney of I-R rats revealed severe renal damage. Importantly, cytoprotective effects of the dual treatment in comparison with H2 treatment and I-R renal injury were observed in terms of superoxide radical scavenging activity and histochemical features. Rats given dual treatment and I-R renal injury showed significant decreases in blood urea nitrogen. Increased expression of several inflammatory cytokines (tumor necrosis factor-α, interleukin-6, intracellular adhesion molecule-1, nuclear factor-κB, hypoxia inducible factor-1α, and heme oxygenase-1) was attenuated by the dual treatment. CONCLUSIONS: Dual gas inhalation decreases oxidative stress and markedly improves I-R-induced renal injury.

A distinct function of the retinoblastoma protein in the control of lipid composition identified by lipidomic profiling.

Here, by combining lipidomics with transcriptome analysis, we demonstrate that Rb depletion in mouse embryonic fibroblastss induces significant alterations in their lipid composition. We discovered that Rb depletion induced increase in lysophosphatidylserine, diacylglycerol (DAG), fatty acid (FA), acylcarnitine, phosphatidylcholine (PC), arachidonoyl ethanolamine, and decrease in phosphatidylglycerol, monoacylglycerol, without change in total lipid per protein levels. Analysis of the acyl chain composition of DAG, PC and phosphatidylserine revealed increase of saturated and mono-unsaturated acyl chains with specific carbon chain length. Consistently, we observed that Rb depletion increased the levels of fatty acids with the corresponding carbon chain length and number of carbon-carbon double bondssuch as myristic acid (14:0), palmitic acid (16:0), stearic acid (18:0) and all forms of FA 18:1. Microarray analysis revealed that Rb depletion induced significant upregulation of enzymes involved in elongation and desaturation of fatty acids. Among these, we found that elongation of long chain fatty acid family member 6 (Elovl6) and stearoyl-CoA desaturase 1 (Scd1) are the most robustly controlled by Rb possibly through E2F and sterol regulatory element-binding protein transcription factors. Depletion of Elovl6 or Scd1 significantly suppressed colony formation, sphere formation and xenograft tumor growth of Rb-deficient tumor cells. Suppression of self-renewal by the SCD1 inhibitor was rescued upon supplementation of the mono-unsaturated fatty acids generated by this enzyme. This study suggests a novel role for Rb in suppressing the malignant progression of tumors by controlling the lipid composition.

A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder.

Background: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. Patients and methods: Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1 mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1 mg or 2 mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety. Results: S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1 mg (100%) and 2 mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide. Conclusion: S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder. Trial registration ID: JapicCTI-090980.

Survey of patient exposure from general radiography and mammography in Japan in 2014.

With the objective of reducing patient exposure to radiation, we conducted a questionnaire survey regarding radiographic conditions in 2014. Here we report estimates of dose exposure in general radiography and mammography through an investigation and comparison of present patient exposure conditions. Questionnaires were sent to 3000 facilities nationwide in Japan. Surveys asked questions on a total of 16 items related to general radiography, including the chest, abdomen, and breast. Output data from x-ray tubes measured in the Chubu area of Japan were used as the mean in these estimates. The index of patient exposure was adopted as the entrance skin dose (ESD) for general radiography and as the mean glandular dose (MGD) for mammography. The response rate for this survey was 21.9%. Our results showed that doses received through the use of flat-panel detector (FPD) devices were lower than those received through computed radiography devices, except for the ankle joint (e.g. in chest examination, the dose from FPD and CR was 0.24 mGy, 0.31 mGy on the average, respectively). These results suggest that more widespread use of FPD devices could lead to decreases in the ESD and MGD, thereby reducing patient exposure.

Results of a 2011 national questionnaire for investigation of mean glandular dose from mammography in Japan.

Diagnostic reference levels (DRLs) for mammography have yet to be created in Japan. A national questionnaire investigation into radiographic conditions in Japan was carried out for the purpose of creating DRLs. Items investigated included the following: tube voltage; tube current; current-time product; source-image distance; craniocaudal view; automatic exposure control (AEC) settings; name of mammography unit; image receptor system (computed radiography (CR), flat panel detector (FPD), or film/screen (F/S)); and supported or unsupported monitor diagnosis (including monitor resolution). Estimation of the mean glandular dose (MGD) for mammography was performed and compared with previous investigations. The MGD was 1.58(0.48) mGy, which did not significantly differ from a 2007 investigation. In relation to image receptors, although no difference in average MGD values was observed between CR and FPD systems, F/S systems had a significantly decreased value compared to both CR and FPDs. Concerning digital systems (FPDs), the MGD value of the direct conversion system was significantly higher than the indirect conversion system. No significant difference in MGD value was evident concerning type of monitor diagnosis for either the CR or the FPD digital systems; however, hard copies were used more often in CR. No significant difference in the MGD value was found in relation to monitor resolution. This report suggests ways to lower the doses patients undergoing mammography receive in Japan, and serves as reference data for 4.2 cm compressed breast tissue of 50% composition DRLs. Furthermore, our findings suggest that further optimisation of FPD settings can promote a reduction in the MGD value.

Recipientes e substratos na produção de mudas e no cultivo hidropônico de tomilho (Thymus vulgaris L. ) / Containers and substrates on seedling production and hydroponic cultivation of thyme (Thymus vulgaris L. )

Bandejas com diferente número de células (128, 200 e 288) e dois substratos (fibra de casca de coco e casca de pinus) foram avaliados para a produção de mudas de tomilho e sobre o desempenho das plantas em sistema hidropônico. Para ambos os experimentos, o delineamento foi em blocos ao acaso. As mudas provenientes de estaquia foram avaliadas aos 30 dias quanto ao comprimento e massa seca de raízes. Aos 40 dias após o transplante das mudas, as plantas cultivadas em sistema hidropônico foram avaliadas quanto à massa fresca da parte aérea, massa seca da parte aérea e massa seca das raízes. A maior massa seca de raízes foi obtida para as mudas cultivadas em substrato à base de casca de fibra de coco. As mudas com maior comprimento de raízes foram obtidas nas bandejas com 128 e 200 células. As plantas de tomilho provenientes de mudas produzidas em bandejas de 128 células apresentaram maior massa fresca da parte aérea, massa seca da parte aérea e massa seca das raízes.

Trays with different number of cells (128, 200 and 288) and two substrates (coir and pine bark-based) were studied for thyme seedling production and plant development in hydroponic system. In both experiments, experimental design was in randomized blocks. Seedlings from cuttings were evaluated at 30 days as to root length and dry matter. At 40 days after transplanting, plants grown in hydroponic system were evaluated for shoot fresh matter, shoot dry matter and root dry matter. The highest root dry matter was detected in seedlings grown in coir-based substrate. Seedlings that presented the greatest root length were obtained by using trays with 128 and 200 cells. Thyme plants from seedlings produced in trays with 128 cells had higher shoot fresh matter, shoot dry matter and root dry matter.

Comparison of sensitivity of lung nodule detection between radiologists and technologists on low-dose CT lung cancer screening images.

OBJECTIVES: The objective of this study was to compare the sensitivity of detection of lung nodules on low-dose screening CT images between radiologists and technologists. METHODS: 11 radiologists and 10 technologists read the low-dose screening CT images of 78 subjects. On images with a slice thickness of 5 mm, there were 60 lung nodules that were ≥5 mm in diameter: 26 nodules with pure ground-glass opacity (GGO), 7 nodules with mixed ground-glass opacity (GGO with a solid component) and 27 solid nodules. On images with a slice thickness of 2 mm, 69 lung nodules were ≥5 mm in diameter: 35 pure GGOs, 7 mixed GGOs and 27 solid nodules. The 21 observers read screening CT images of 5-mm slice thickness at first; then, 6 months later, they read screening CT images of 2-mm slice thickness from the 78 subjects. RESULTS: The differences in the mean sensitivities of detection of the pure GGOs, mixed GGOs and solid nodules between radiologists and technologists were not statistically significant, except for the case of solid nodules; the p-values of the differences for pure GGOs, mixed GGOs and solid nodules on the CT images with 5-mm slice thickness were 0.095, 0.461 and 0.005, respectively, and the corresponding p-values on CT images of 2-mm slice thickness were 0.971, 0.722 and 0.0037, respectively. CONCLUSION: Well-trained technologists may contribute to the detection of pure and mixed GGOs ≥5 mm in diameter on low-dose screening CT images.

Feasibility of delta-shaped anastomoses in totally laparoscopic distal gastrectomy.

BACKGROUND: Delta-shaped (DS) anastomosis is a new reconstruction method for totally laparoscopic distal gastrectomy (TLDG) using a linear stapler. We evaluated the feasibility of using this method for TLDG. METHODS: A retrospective analysis was performed in 114 patients who underwent TLDG with DS anastomosis. Twenty-four patients reconstructed with a Roux-en-Y (RY) anastomosis during the same period were analyzed as control subjects. RESULTS: The patient characteristics of DS and RY anastomoses were slightly different in terms of tumor location and extent of lymph node dissection, since this was not a prospective comparative study. Blood loss, postoperative complication rate and postoperative hospital stay were not different between the two groups. There was only 1 case of anastomotic leakage, and no case of anastomotic stricture after DS anastomosis. The length of the operation using DS anastomosis was significantly shorter than for RY anastomosis. The rates of body weight loss were not significantly different at 1 year after the operation. CONCLUSIONS: Although this was a small retrospective analysis, DS anastomosis was feasible, required a shorter operation time, and had no associated complications. This method can therefore be recommended as a standard procedure for TLDG.

Potentiation of ghrelin signaling attenuates cancer anorexia-cachexia and prolongs survival.

Cancer anorexia-cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut-brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia-cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia-cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia-cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia-cachexia.

Role of lymph node dissection in the treatment of urothelial carcinoma of the upper urinary tract: multi-institutional relapse analysis and immunohistochemical re-evaluation of negative lymph nodes.

AIM: To determine the role of lymph node dissection (LND) in the treatment of urothelial carcinoma (UC) of the upper urinary tract (UUT). PATIENTS AND METHODS: [Study-1] A retrospective multi-institutional study evaluated 293 patients undergoing predominantly nephroureterectomy for UC of the UUT. Of 293 patients, 267 patients had pure UC and 26 demonstrated other histological components. Regarding the pathological node status, 130 patients had pN0 disease, 141 patients had pNx disease and 22 patients had pN+ disease. The sites of initial recurrence and time to first recurrence were reviewed. The sites of recurrence were classified as locoregional or distant recurrence. The relationship between node status and future recurrence was analyzed. [Study-2] Fifty-one patients treated by nephroureterectomy at Hokkaido University Hospital were included. All had LND and all LNs were negative on hematoxylin and eosin staining. We re-evaluated the presence of micrometastasis in LND specimens by anti-cytokeratin immunohistochemistory. RESULTS: [Study-1] Of 293 patients, 76 developed disease relapse. Regional lymph node recurrence was the most common site (34 patients). On multivariate analyses that adjusted for the effect of tumor stage and tumor grade, pNx (skipping LND) was an adverse factor not only for locoregional recurrence, but also for distant relapse. [Study-2] Immunohistochemistry identified micrometastases in 7 (14%) of 51 patients. Regarding survival, 5 of these 7 patients with micrometastases were alive at last follow-up. CONCLUSIONS: On relapse analysis, skipping LND was an adverse factor not only for locoregional recurrence, but also for distant relapse. Immunohistochemistry detected micrometastases in about 14% of patients previously diagnosed as pN0. These findings further support a potential therapeutic benefit of LND by eliminating micrometastases.

Hypertrophic obstructive cardiomyopathy with Schmidt's syndrome: report of a case.

Schmidt's syndrome is an autoimmune disease, which can present as a complication of idiopathic Addison's disease and chronic thyroiditis (Hashimoto's disease), and may cause acute adrenal insufficiency in the presence of stress such as surgery. In this study, we report a patient with hypertrophic obstructive cardiomyopathy (HOCM) complicated by Schmidt's syndrome who did not develop any complications after surgery.

Efficacy of neutrophil elastase inhibitor on type A acute aortic dissection.

BACKGROUND: Surgery for type A acute aortic dissection (AAD) is associated with a high mortality and incidence of postoperative complications, including acute respiratory failure and coagulopathy. Aim of the study was to investigate the effects of sivelestat on pulmonary function and coagulopathy in patients undergoing surgery for AAD. METHODS: Sixty patients undergoing emergency ascending replacement for AAD were divided into two groups. Group I was administered sivelestat intravenously from the beginning of surgery until extubation. Group II was not treated with sivelestat. The platelet count, antithrombin III (AT III) level, leukocyte count, C-reactive protein (CRP) level, prothrombin time (PT), activated partial thrombin time (APTT), and prothrombin time-international normalized ratio (PT-INR) were measured. RESULTS: The postoperative decrease of AT III and the platelet count on admission to the intensive care unit (ICU) and 3 hours later were significantly less in group I. The leukocyte count and the values of CRP, PT, APTT, and PT-INR did not differ significantly between the groups. The duration of mechanical ventilation after surgery tended to be shorter in group I. CONCLUSIONS: Sivelestat significantly reduced the postoperative decreases in AT III and platelet count in patients undergoing emergency surgery for AAD.

[Does aortic cusp repair influence the outcome of valve sparing aortic root replacement?].

BACKGROUND: Outcome of the patients who underwent aortic root replacement with valve sparing procedure concomitant with cusp repair was evaluated. METHODS: Between October 1999 and April 2009, valve sparing aortic root replacement were performed in 62 patients. Isolated valve sparing procedure was performed in 38 patients (control) and concomitant cusp repair was performed in 24 patients (aortic valve plasty: AVP). Cusp prolapse was corrected by plication of Arantius body (n = 13), cusp perforations were closed by pericardial patch (n = 6) or reinforcement of free margin (n = 6). RESULTS: No patient died during the hospital stay and no thromboembolic events occurred in the follow up. Pre-operative grade of aortic insufficiency was 3.0 +/- 0.9 in AVP group vs. 2.5 +/- 1.3 in control (NS). There was no significant difference between both groups regarding age, cardiac function and preoperative aortic root diameter. However, eccentric jet by preoperative transesophageal echocardiography (TEE) was more often in group AVP than in control (p<0.01). Five patients underwent reoperation because of recurrent aortic regurgitation (AR) or hemolysis. Postoperative AR grade were similar in both groups (0.9 +/- 0.5 vs 0.5 +/- 0.6). During follow up, the 5 year freedom from re-operation (aortic valve replacement: AVR) was 85.1+/- 8.2% in AVP and 94.0 +/- 4.1% in control (NS). 5-year-survival was 100% and 95.0 +/- 4.9% (NS), respectively. CONCLUSIONS: Valve sparing aortic root replacement with concomitant cusp repair provided satisfactory midterm result.

Pulmonary embolism with myomatous erythrocytosis syndrome and extreme obesity.

We here report a case of a 53-year-old woman requiring pulmonary embolectomy for acute massive pulmonary embolism caused by a huge uterine myoma compressing veins in the pelvis and extreme obesity. She was also diagnosed as having myomatous erythrocytosis syndrome, a rare disease associated with secondary polycythemia. The polycythemia improved after a hysterectomy which was performed after pulmonary embolectomy.

[Approaches and results in video-assisted thoracic surgery lobectomy for the patient with primary lung cancer].

Video-assisted thoracic surgery (VATS) lobectomy is defined as a video-assisted procedure using anatomic dissection with individual ligation of the vessels and bronchi. VATS lobectomy can offer several advantages, including decreased pain, and decreased inflammatory response. The patient is placed in the lateral decubitus position. A 12-mm port is inserted in the 7th intercostal space at the midaxillary line. A 8-cm utility incision is created in the axilla at the 4th intercostal space for upper or middle lobectomy. For lower lobectomy, a 8-cm utility incision is created in the auscultatory triangle at the 5th intercostal space. A 12-mm incision is frequently placed near the utility incision in the 6th intercostal space, particularly when using retraction for improved exposure or for insertion of added instrumentation. We performed the hilar vessel ligation using endoscopic ligation forceps SAITO model (Japan patent no. 4148324). We reported approaches and techniques in our hospital for the patients who underwent VATS lobectomy based on the surgical databases from the Division of Thoracic Surgery at the Kansai Medical University Hirakata Hospital during the period from January 5, 2006 through August 31, 2008.

Comparison of postoperative surface light scattering of different intraocular lenses.

AIMS: This retrospective study was conducted to compare postoperative surface scattering of four kinds of intraocular lens (IOL). METHODS: Sixty-seven eyes of 67 patients who had undergone cataract surgery were enrolled in this study. One of four IOLs was used in the patients; MA60BM in 17 patients (MA group), SA60AT in 17 patients (SA group), AR40 in 16 patents (AR group) and ClariFlex in 17 patients (CL group). Measurement of scattering from the anterior surface of the IOL was measured with area densitometry using a Scheimpflug camera (EAS-1000, Nidek, Aichi) for 3 years after the surgery. RESULTS: The density of IOL surface scattering increased starting 1 year after surgery and throughout the 3-year period in the MA group and starting at 6 months through 3 years in the SA group, whereas the density was stable in the AR and CL groups. The density of surface scattering in the MA and SA groups at 3 years after surgery was significantly higher than in the AR and CL groups. CONCLUSION: The surface scattering of MA60BM and SA60AT is higher than that of AR40 and ClariFlex. The grades of surface scattering differ among the manufacturers, even with the same acrylic material.

Detectability of peripheral lung cancer on chest radiographs: effect of the size, location and extent of ground-glass opacity.

The purpose of this study was to evaluate the effect of the size and location of lung tumour and the extent of ground-glass opacity (GGO) on thin-section CT for the detection of peripheral lung cancer on chest radiographs. 100 posteroanterior chest radiographs of peripheral lung cancer 20 mm in diameter or smaller were reviewed retrospectively by two chest radiologists individually. Lung cancer was detectable on chest radiographs in 51 (51%) cases. However, in six cases, the tumour was recognized not as a nodular opacity but as a subpleural linear or localized hazy opacity. The median size of detectable lung cancer (17 mm) was larger than that of undetectable lung cancer (14 mm; p<0.001). The frequency of tumours with extent of GGO less than 70% was 94% in detectable cases and 59% in undetectable cases (p<0.001). The frequency of tumours located in unobscured lung was 94% in detectable cases and 59% in undetectable cases (p<0.001). The detectability of peripheral lung cancer on chest radiographs is influenced by tumour size, location and extent of GGO seen on thin-section CT. It should also be noted that some tumours may not be recognized as a nodular opacity even if they are detectable.

Proton pump inhibitors may increase the risk of delayed bleeding complications after open heart surgery if used concomitantly with warfarin.

OBJECTIVES: The American Food and Drug Administration has suggested that proton pump inhibitors increase the international normalized ratio (INR) when used concomitantly with warfarin, by being metabolized by cytochrome P450 2C19. We therefore reviewed patients taking warfarin. METHODS AND RESULTS: Two hundred and forty patients who took warfarin after surgery were divided into two groups: Group I (n = 114) had rabeprazole (10 mg/day) and Group II (n = 126) had lansoprazole (15 mg/day). The initial dose of warfarin was 3 mg and INR was initially assessed on postoperative day 4. Initial INR was significantly lower in Group I (1.66 +/- 0.87) than in Group II (2.06 +/- 1.03, P = 0.0011). Delayed cardiac tamponade and hemothorax occurred as complications in 6 and 1 patients, respectively, in Group II from 5 days to 3 months postoperatively. At the time of the occurrence of complications, the average INR increased to 3.95 (range from 3.11 to 5.86). There were no patients with delayed bleeding in Group I ( P = 0.015). CONCLUSIONS: These results suggest that lansoprazole emphasizes the effects of warfarin. Rabeprazole could be safely used concomitantly with warfarin.