Detailed Superiority of the CAD EYE Artificial Intelligence System over Endoscopists for Lesion Detection and Characterization Using Unique Movie Sets.

Objectives: Detailed superiority of CAD EYE (Fujifilm, Tokyo, Japan), an artificial intelligence for polyp detection/diagnosis, compared to endoscopists is not well examined. We examined endoscopist's ability using movie sets of colorectal lesions which were detected and diagnosed by CAD EYE accurately. Methods: Consecutive lesions of ≤10 mm were examined live by CAD EYE from March-June 2022 in our institution. Short unique movie sets of each lesion with and without CAD EYE were recorded simultaneously using two recorders for detection under white light imaging (WLI) and linked color imaging (LCI) and diagnosis under blue laser/light imaging (BLI). Excluding inappropriate movies, 100 lesions detected and diagnosed with CAD EYE accurately were evaluated. Movies without CAD EYE were evaluated first by three trainees and three experts. Subsequently, movies with CAD EYE were examined. The rates of accurate detection and diagnosis were evaluated for both movie sets. Results: Among 100 lesions (mean size: 4.7±2.6 mm; 67 neoplastic/33 hyperplastic), mean accurate detection rates of movies without or with CAD EYE were 78.7%/96.7% under WLI (p<0.01) and 91.3%/97.3% under LCI (p<0.01) for trainees and 85.3%/99.0% under WLI (p<0.01) and 92.6%/99.3% under LCI (p<0.01) for experts. Mean accurate diagnosis rates of movies without or with CAD EYE for BLI were 85.3%/100% for trainees (p<0.01) and 92.3%/100% for experts (p<0.01), respectively. The significant risk factors of not-detected lesions for trainees were right-sided, hyperplastic, not-reddish, in the corner, halation, and inadequate bowel preparation. Conclusions: Unique movie sets with and without CAD EYE could suggest it's efficacy for lesion detection/diagnosis.

Efficacy of hemostatic gel for perioperative bleeding and prevention of delayed bleeding of cold snare polypectomy under anticoagulant.

Background and Aim: A hemostatic gel, PuraStat (3-D Matrix, Tokyo, Japan), is used for various gastrointestinal hemostasis. In this study, we analyzed the efficacy of PuraStat for perioperative bleeding (POB) and prevention of delayed bleeding (DB) to colorectal cold snare polypectomy (CSP) with continuous anticoagulant. Methods: This was a single-center, retrospective study. Subjects were lesions of 2-9 mm under continuous anticoagulant from 2021 to 2023 and treated with PuraStat for POB. The definition of POB was bleeding which did not stop spontaneously by 1.0-1.5 min after resection and needed hemostasis. Successful hemostasis was defined as cessation of bleeding within 1.0-1.5 min after spraying PuraStat and the rate of it and risk factors of POB were analyzed. For comparison, cases receiving previous CSP without PuraStat were extracted from all cases with CSP (2018-2021), and POB and DB rate (DBR) were analyzed after propensity score matching. Results: One hundred twenty-two lesions (91: direct oral anticoagulant (DOAC), 31: warfarin) with anticoagulant were analyzed and the rate of successful hemostasis with PuraStat was 92.6% (DOAC/warfarin: 93.4%/80.6%, P = 0.01). The rate of DB was 0.0%. Multivariate analysis showed that significant risk factors about unsuccessful hemostasis for POB with PuraStat were lesion size 8-9 mm (P < 0.01), warfarin (P = 0.01), and combination of antiplatelet (P = 0.01). Regarding the comparison about CSP with/without PuraStat, the clipping rate and DBR were 8.5%/94.9% (P < 0.01) and 0%/1.7% (P = 1.0). Conclusion: The effects of PuraStat for POB and DB in colorectal CSP with continuous anticoagulant were acceptable.

Additional 30-Second Observation of the Right-Sided Colon for Missed Polyp Detection With Texture and Color Enhancement Imaging Compared with Narrow Band Imaging: A Randomized Trial.

INTRODUCTION: The efficacy of texture and color enhancement imaging (TXI) in the novel light-emitting diode endoscopic system for polyp detection has not been examined. We aimed to evaluate the noninferiority of the additional 30-second (Add-30-s) observation of the right-sided colon (cecum/ascending colon) with TXI compared with narrow band imaging (NBI) for detecting missed polyps. METHODS: We enrolled 381 patients ≥40 years old who underwent colonoscopy from September 2021 to June 2022 in 3 institutions and randomly assigned them to either the TXI or NBI groups. The right-sided colon was first observed with white light imaging in both groups. Second, after reinsertion from hepatic flexure to the cecum, the right-sided colon was observed with Add-30-s observation of either TXI or NBI. The primary endpoint was to examine the noninferiority of TXI to NBI using the mean number of adenomas and sessile serrated lesions per patient. The secondary ones were to examine adenoma detection rate, adenoma and sessile serrated lesions detection rates, and polyp detection rates in both groups. RESULTS: The TXI and NBI groups consisted of 177 and 181 patients, respectively, and the noninferiorities of the mean number of adenomas and sessile serrated lesions per patients in the second observation were significant (TXI 0.29 [51/177] vs NBI 0.30 [54/181], P < 0.01). The change in adenoma detection rate, adenoma and sessile serrated lesions detection rate, and polyp detection rate for the right-sided colon between the TXI and NBI groups were not different (10.2%/10.5% [ P = 0.81], 13.0%/12.7% [ P = 0.71], and 15.3%/13.8% [ P = 0.71]), respectively. DISCUSSION: Regarding Add-30-s observation of the right-sided colon, TXI was noninferior to NBI.

The Efficacy of 480 ml Oral Sodium Sulfate for Improving Insufficient Bowel Preparation of Colonoscopy with High-Concentrated Polyethylene Glycol.

Objectives: Oral sulfate solution (OSS) is used for bowel preparation (BP) during colonoscopy. The way of taking this agent can be used a same-day regimen (only on the day of colonoscopy) and split regimen (the day before and on the day of colonoscopy) for receiving it. In this study, we analyzed the efficacy of a same-day regimen of 480 ml OSS for insufficient bowel preparation (BP) with high-concentrated polyethylene glycol (H-PEG). Materials and Methods: This multicenter retrospective study was conducted from December 2021 to December 2022 at three related institutions on patients aged ≥ 20 years with a fair or poor Aronchick score of BP with 1 l H-PEG in previous colonoscopy. All patients received a low-residual diet and 10 ml of 0.75% picosulfate sodium a day before the colonoscopy and 480 ml of OSS and ≥1 l of water 3 hours before the colonoscopy. We analyzed the rate of improvement with OSS compared to H-PEG and other efficacies, and adverse events (AE). Results: We evaluated 125 cases (77 males) with an average age of 72.1 ± 8.8 years. The completion rate of 480 ml of OSS was 97.6% (122/125). The improvement rate of BP showing good or excellent score with OSS was 70.4% (88/125). Compared OSS with previous H-PEG, the insertion time (min) was 7.0 ± 4.8 vs. 8.1 ± 6.0 (p = 0.01), and the adenoma detection rates were 67.2% vs. 63.2% (p = 0.05). The cleansing time (min) was 131 ± 46 vs. 165 ± 53 (p < 0.01). The rate of AE with OSS was 10.4% (13/125). There were no significant differences about AE in age and gender. The tolerance of OSS compared with H-PEG (good/similar/bad) was 72.0%/24.8%/3.2% (amounts), 26.4%/39.2%/34.4% (taste), and 76.8%/10.4%/12.8% (overall preference), respectively. Conclusions: The same-day regimen of 480 ml OSS effectively improved the insufficient BP of 1 l H-PEG.

Growth conditions inducing G1 cell cycle arrest enhance lipid production in the oleaginous yeast Lipomyces starkeyi.

Lipid droplets are cytoplasmic organelles that store lipids for energy and membrane synthesis. The oleaginous yeast Lipomyces starkeyi is one of the most promising lipid producers and has attracted attention as a biofuel source. It is known that the expansion of lipid droplets is enhanced under nutrient-poor conditions. Therefore, we prepared a novel nitrogen-depleted medium (N medium) in which to culture L. starkeyi cells. Lipid accumulation was rapidly induced, and this was reversed by the addition of ammonium. In this condition, cell proliferation stopped, and cells with giant lipid droplets were arrested in G1 phase. We investigated whether cell cycle arrest at a specific phase is required for lipid accumulation. Lipid accumulation was repressed in hydroxyurea-synchronized S phase cells and was increased in nocodazole-arrested G2/M phase cells. Moreover, the enrichment of G1 phase cells seen upon rapamycin treatment induced massive lipid accumulation. From these results, we conclude that L. starkeyi cells store lipids from G2/M phase and then arrest cell proliferation in the subsequent G1 phase, where lipid accumulation is enhanced. Cell cycle control is an attractive approach for biofuel production.

Eosinophilic Cholangitis with Poor Prognosis after Corticosteroid- and Ursodeoxycholic Acid-Related Remission of Peripheral and Peribiliary Eosinophilia.

A 79-year-old man presented with high fever, marked eosinophilia, altered biochemical liver function tests (LFT) with predominance of biliary enzymes, and severe wall thickening of the gallbladder. Magnetic resonance cholangiopancreatography (MRCP) suggested cholecystitis, without signs of biliary strictures. Laparoscopic cholecystectomy and exploratory liver excision revealed eosinophilic cholangitis and cholecystitis, complicated with hepatitis and portal phlebitis. Prednisolone monotherapy rapidly improved peripheral eosinophilia, but not LFT. Liver biopsy showed that infiltrating eosinophils were replaced by lymphocytes and plasma cells. Treatment with ursodeoxycholic acid improved LFT abnormalities. Nevertheless, after 2 months, transaminase-dominant LFT abnormalities appeared. Transient prednisolone dose increase improved LFT, but biliary enzymes' levels re-elevated and jaundice progressed. The second and third MRCP within a 7-month interval showed rapid progression of biliary stricture. The repeated liver biopsy showed lymphocytic, not eosinophilic, peribiliary infiltration and hepatocellular reaction to cholestasis. Eighteen months after the first visit, the patient died of hepatic failure. Autopsy specimen of the liver showed lymphocyte-dominant peribiliary infiltration and bridging fibrosis due to cholestasis. Though eosinophil-induced biliary damage was an initial trigger, repeated biopsy suggested that lymphocytes played a key role in progression of the disease. Further studies are needed to elucidate the relationship between eosinophils and lymphocytes in eosinophilic cholangitis.

[A case of gastrointestinal amyloidosis and hypoproteinemia improved by tocilizumab].

A woman in her 70s presented with dehydration and malnutrition due to watery diarrhea. She was examined and diagnosed with gastrointestinal amyloidosis accompanied by a protein-losing gastroenteropathy secondary to rheumatoid arthritis. She first underwent treatment with an anti-tumor necrosis factor alpha (TNF-α) antibody for secondary amyloidosis, but due to lack of adequate response, she was switched to an anti-interleukin (IL)-6 receptor antibody. Her clinical symptoms subsequently improved, and endoscopy revealed a marked decrease of amyloid protein deposits in the digestive tract. She was followed up for 3 years while continuing to receive the anti-IL-6 receptor antibody, with no recurrence. Although secondary amyloidosis is a fatal disease associated with chronic inflammatory diseases, clinical symptoms and prognosis have recently been improved by intervention with biological therapies. In particular, anti-IL-6 receptor antibodies have been reported to be superior to anti-TNF-α antibodies in the treatment of secondary amyloidosis and are expected to play a central role in treating secondary amyloidosis in the future.

High incidence of metachronous advanced adenoma and cancer after endoscopic resection of colon polyps ≥20 mm in size.

BACKGROUND AND AIM: There are limited studies on incidence rates of metachronous neoplastic lesions after resecting large colorectal polyps. In the present study, we analyzed metachronous lesions after endoscopic resection of colorectal polyps ≥20 mm in size. METHODS: We retrospectively analyzed consecutive patients who underwent endoscopic resection of polyps from 2006 to 2013 at two affiliated hospitals. All patients underwent at least two total colonoscopies before follow up to ensure minimal missed polyps. Only patients who had follow-up colonoscopy annually after resection were recruited. We separated patients according to size of polyp resected; there were 239 patients in the ≥20-mm group and 330 patients in the <20-mm group. Clinical characteristics and cumulative rates of metachronous advanced adenoma and cancer in both groups were analyzed. Advanced adenoma was defined as a neoplastic lesion ≥10 mm in size and adenoma with a villous component. RESULTS: Cumulative rate of development of metachronous advanced adenoma and cancer in the ≥20-mm group was significantly higher than in the <20-mm group (22.9% vs. 9.5%, P < 0.001) at 36 months. There was also more development of small polyps 5-9 mm in the ≥20-mm group than in the <20-mm group (45.2% vs. 28.8%, P < 0.001). With respect to metachronous lesions, there were more right-sided colonic lesions in the ≥20-mm group than in the <20-mm group (78.8% vs. 50.0%, P = 0.015). CONCLUSION: High incidence rates of development of metachronous neoplastic lesions were detected after resection of colorectal polyps ≥20 mm in size.

The detection of surface patterns by flexible spectral imaging color enhancement without magnification for diagnosis of colorectal polyps.

PURPOSE: Flexible spectral imaging color enhancement (FICE), or image-enhanced endoscopy, can enhance visualization of surface and vascular patterns of colorectal polyps. Resolution of FICE has recently been improved. We evaluated diagnostic accuracy for neoplastic and non-neoplastic colorectal polyp differentiation with detection of surface patterns by FICE without magnification. METHODS: Retrospective analysis of 151 colorectal polyps evaluated by FICE without magnification was performed. Neoplastic surface patterns were defined as tubular and oval pit. We aimed to determine sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy in correlating diagnosis by FICE without magnification with histology. Moreover, findings were compared to those of white-light endoscopy (WL) and chromoendoscopy (CHR). RESULTS: Of the 151 colorectal polyps, 95 were identified as neoplastic and 56 were identified as non-neoplastic. FICE without magnification had a sensitivity of 89.4%, specificity of 89.2%, PPV of 93.4%, NPV of 83.3%, and accuracy of 89.4%. The accuracy of FICE value was higher than that of WL (sensitivity of 74.7%, specificity of 73.2%, PPV of 82.5%, NPV of 63.0%, and accuracy of 74.1%) and was worse than that of CHR (sensitivity of 96.8%, specificity of 89.2%, PPV of 93.9%, NPV of 96.1%, and accuracy of 94.7%). Imaging evaluation was validated by inter-/intra-observer measurements, demonstrating consistent results. CONCLUSIONS: The detection of surface patterns by FICE without magnification is useful for differential diagnosis of colorectal polyps. We believe that FICE without magnification is more convenient and easier method than CHR.

Efficacy of hyaluronic acid in endoscopic mucosal resection of colorectal tumors.

BACKGROUND AND AIM: Endoscopic mucosal resection (EMR) is the standard procedure for colorectal tumors. High mucosal elevation by submucosal injection is important for definite en bloc resection and the prevention of perforation. Hyaluronic acid (HA) is a reportedly useful injection solution for high and long-lasting mucosal elevation, but the ideal HA concentration for optimization of mucosal elevation maintenance, injection pressure, and cost is unknown. In the present study, we assessed the appropriate concentration of HA for EMR. METHODS: A resected porcine colon and esophagus were used. The injection solutions examined were 0.9% normal saline (NS) and four concentrations of an 800-KDa HA preparation (0.4%, 0.2%, 0.13%, and 0.1%). Each solution (2 mL) was injected into the submucosa; injection pressure was calculated, and elevation was measured. The durations of mucosal elevation and EMR were additionally assessed in the living minipig colon. RESULTS: In the resected porcine colon, the mucosal elevation was measured 0, 2, 4, and 6 min after the submucosal injection. All concentrations of HA solution maintained greater mucosal elevation at all times than NS (P < 0.05). An almost similar result was obtained in the resected porcine esophagus. The injection pressure correlated with the HA concentration. In the living minipig colon, mucosal elevation diminished 2 min after the submucosal injection with NS, but was maintained 2 min after injection with 0.4%, 0.2%, and 0.13% HA. The average duration of EMR was 139 s. CONCLUSIONS: Mucosal elevation by HA was greater than that by NS in resected and living animal models. We recommend 0.13% HA for maintaining mucosal elevation, injection pressure, and cost.

Efficacy of magnifying endoscopy with flexible spectral imaging color enhancement in the diagnosis of colorectal tumors.

BACKGROUND: Magnifying endoscopy with flexible spectral imaging color enhancement (FICE) is an image-enhanced endoscopy that captures the surface and vascular patterns of colorectal tumors. We evaluated and compared FICE magnification to narrow-band imaging (NBI) magnification. METHODS: Flexible spectral imaging color enhancement or NBI magnification was performed to the visualize surface and vascular patterns of colorectal tumors, classified into 4 types: Type A, Type B, Type C1/C2, and Type C3, as previously reported. A total of 235 colorectal tumors were examined. The correlations between classifications found by FICE or NBI magnification and histopathological diagnoses were examined. Image evaluation was validated by assessing inter-observer and intra-observer agreements on examinations. RESULTS: Twenty-eight hyperplastic polyps (HPs), 115 tubular adenomas (TAs), 72 mucosal and slightly invaded submucosal cancers (M-sSM), and 20 massively invaded submucosal cancers (mSM) were diagnosed. By FICE magnification, HP and TA were observed in 93.3 and 6.7% of Type A (15 lesions), respectively. TA, M-sSM, and HP were observed in 82.6, 15.4, and 2.0% of Type B (52 lesions),respectively. M-sSM, TA, and mSM were observed in 50.0,46.0, and 4.0% of Type C1/2 (50 lesions), respectively.mSMs were observed in all 7 Type C3 lesions. In diagnosing mSM in Type C3, the sensitivity and specificity of FICE magnification were 77.7 and 100%, respectively, compared to those of NBI, at 63.6 and 99.0%, respectively. Imaging evaluation was validated accurately by intra- and intraobserver measurements showing consistent results. CONCLUSIONS: The classification of colorectal tumors by FICE magnification correlated well with the histopathological diagnoses, similar to findings for NBI magnification. FICE magnification can be evaluated accurately with the same diagnostic classifications as those used for NBI magnification.

Evaluation of autofluorescence colonoscopy for diagnosis of superficial colorectal neoplastic lesions.

BACKGROUND AND AIM: Autofluorescence (AF) imaging, which can potentially differentiate tissue types based on differences in fluorescence emission, may be useful in the diagnosis and treatment of colorectal malignancies. This study was designed to assess the potential usefulness of AF colonoscopy for evaluating superficial colorectal neoplastic lesions. METHODS: A total of 49 colorectal lesions in 43 patients were investigated. All superficial colorectal neoplastic lesions were identified with white light (WL) colonoscopy. Each detected lesion was investigated by WL colonoscopy, AF colonoscopy, and chromoendoscopy using 0.2% indigo carmine dye. Three endoscopists, blinded to each patient's history, evaluated the still images (as obtained with these three methods) in random order and evaluated their influence on the assessment of lesion visualization. All the lesions were biopsied or resected endoscopically, with the pathological results used as the gold standard. RESULTS: For visualization of the surface appearance and differences in color of the lesions compared with the surrounding mucosa, AF colonoscopy was superior to WL colonoscopy (p < 0.01) and comparable to chromoendoscopy (Mann-Whitney U test). For visualization of the circumferential margin, AF colonoscopy was superior to WL colonoscopy (p < 0.05) but inferior to chromoendoscopy (p < 0.01). CONCLUSIONS: AF colonoscopy may be a valuable tool for detection and diagnosis of superficial colorectal neoplastic lesions.

Outcome of endoscopic submucosal dissection for colorectal tumors in elderly people.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been reported to be effective for the en bloc resection of large colorectal tumors. Our study investigated whether ESD was suitable for elderly people with large colorectal tumors in terms of its invasiveness. PATIENTS AND METHODS: We studied 119 colorectal tumors that were treated with ESD at Kyoto Prefectural University of Medicine or Nara City Hospital between 2006 and 2009. We classified each patient as either elderly, i.e., more than 75 years old, or non-elderly, i.e., less than 75 years old. Thirty-two of the cases were classified as elderly. Performance status, tumor size, operation time, rate of en bloc resection, histopathological diagnosis, complications, and hospital stay after ESD were analyzed retrospectively in both groups. RESULTS: In the elderly group, the average tumor size was 32.6 mm; the average operation time, 96 min; the rate of en bloc resection, 81.2%; the rate of perforation, 3.1%; and hospital stay after ESD, 5.1 days. Histopathological diagnosis for 16 tumors was adenoma; for 13, carcinoma with invasion into the mucosa; and for three, carcinoma with invasion into the submucosa. There were no statistical differences between the two groups in any of these data. The case with perforation was treated conservatively without urgent surgery in the elderly group. CONCLUSIONS: ESD for colorectal tumors resulted in favorable rates of en bloc resection in elderly people. Perforation occurred in elderly people, but these patients were cured with conservative treatment. ESD is a safe and minimally invasive treatment for elderly people with colorectal tumors.

Length of vancomycin administration for treatment of clostridium difficile-associated diarrhea may depend on presentation of colonic ulcer.

BACKGROUND/AIMS: Clostridium difficile-associated diarrhea (CDAD) is a notorious iatrogenic infection with typical endoscopic features consisting of pseudomembranes (PMs). Concomitant colonic ulcers are sometimes endoscopically detected. We hypothesized that length of vancomycin (VCM) administration for treatment depends on presentation of colonic ulcer. METHODOLOGY: We investigated retrospectively endoscopic findings and total number of days of vancomycin administration for patients who showed evidence of C. difficile toxin A or PMs at our hospitals. We excluded CDAD cases with inflammatory bowel disease. RESULTS: Sixteen patients were diagnosed as having CDAD. All patients receiving endoscopic examination presented PMs. Two cases had PMs in the transverse and small intestine. The patients with ulcers needed 5-28 days of administration of VCM, while all those without ulcers except one were cured within seven days. CONCLUSIONS: Our results suggest that ulcer may be a factor of poor prognosis, and we recommend endoscopic examination for all patients with CDAD for identification of poor prognostic groups.

Absence of pseudomembranes in Clostridium difficile-associated diarrhea in patients using immunosuppression agents.

OBJECTIVE: Clostridium difficile is a major cause of diarrhea in hospitalized patients. Although pseudomembranes are crucial evidence for diagnosis of C. difficile-associated diarrhea (CDAD), some cases do not show any pseudomembranes. The aim of this study was to verify the hypothesis that pseudomembranes are not generated in immunosuppressed patients because of the absence of immunoreactions. MATERIAL AND METHODS: We investigated the endoscopic findings of patients with ulcerative colitis (UC) or who had received hematopoietic stem cell transplantation, and who presented with C. difficile toxin A and had undergone colonoscopy between April 2002 and July 2007 at our institutes. Results. In 4 patients the diagnosis was UC and C. difficile infection, and in another 4 patients the diagnosis was CDAD after hematopoietic stem cell transplantation. None of these cases showed pseudomembranes. Shallow ulcers were found in all four cases with UC. Only non-specific findings were obtained for the CDAD patients after hematopoietic stem cell transplantation. CONCLUSIONS: Pseudomembranes, the typical evidence for CDAD, were not detected in any patients using immunosuppressive agents. Additional bacterial examination is therefore essential when UC becomes exacerbated and when patients present with diarrhea after hematopoietic stem cell transplantation, even in the absence of pseudomembranes.

Clostridium difficile-associated diarrhea with hematochezia is associated with ulcer formation.

OBJECTIVE: Clostridium difficile-associated diarrhea (CDAD) is a well-known iatrogenic infection with typical endoscopic features including pseudomembranes and intervening normal mucosa. Clinically, diarrhea frequently occurs, but occurrence of hematochezia is rare. The objective of this study was to investigate the background and endoscopic features of CDAD patients with hematochezia. MATERIAL AND METHODS: The endoscopic and clinical findings in 12 patients who showed evidence of C. difficile toxin A and who underwent colonoscopy between April 2002 and July 2007 were investigated retrospectively. RESULTS: Eight patients were diagnosed as having CDAD and 4 patients had a diagnosis of ulcerative colitis. Six of the patients with CDAD presented with hematochezia, and 4 of them were diagnosed with hematological malignancies and received anticancer chemotherapy. Colonic ulcer was demonstrated in all CDAD patients with hematochezia, and bleeding from the ulcer was endoscopically confirmed in all of them. CONCLUSIONS: CDAD accompanied by hematochezia is closely associated with ulcer formation. Ulcers are thought to occur during recovery from nadir after anticancer treatment, and white blood cells appear to be essential for their formation. Physicians should therefore pay close attention to the occurrence of colonic ulcer, especially in patients with CDAD during recovery from nadir.

Population pharmacokinetics of levofloxacin as prophylaxis for febrile neutropenia.

BACKGROUND: Levofloxacin (LVFX) is widely used against a broad spectrum of bacteria. To prevent the emerging of resistance resulting from its abuse, an optimal method and dosage are needed. In the field of hematological malignancies, LVFX is one of the choices for prophylaxis for febrile neutropenia (FN). There is no consensus about the optimal dosage and method among hematologists. Aims To determine the population pharmacological parameters based on the population pharmacokinetics of LVFX. We considered the optimal dosage and method of LVFX based on various simulations depicted by personal computer. METHODS: We performed population pharmacokinetic analysis for seven patients receiving LVFX as prophylaxis (200 mg, b.i.d.) for FN with blood sampling. One patient received 100 mg t.i.d. All patients were treated at Kyoto Prefectural University of Medicine. RESULTS: Clearance (CL) is 5.8 L/hr, distribution volume (Vd) is 58.5 L, area under the blood concentration-time curve (AUC(0-24)) is 69.0 microg x hr/mL, t1/2 is 6.9 hr, Cmax is 3.4 microg/mL at administration of 200 mg b.i.d. Cmax (peak) of 500 mg, and q.d. is simulated as 8.54 microg/mL. CONCLUSION: For LVFX 500 mg q.d. is predicted to be the most effective dosage and method. Because the predicted Cmax value is similar to that of western countries, the frequency of adverse effects is thought to be same as in western countries. 500 mg, q.d., may also be an optimal dosage and method for Japanese.