Integration of Viral Genome to Human Genomic DNA in Nails of Patients with Chronic Hepatitis B Virus Infection.

Introduction: Hepatitis B virus (HBV) DNA and cytomegalovirus (CMV) DNA can be detected in patient genomes. However, it remains unknown whether viral DNA can be integrated into host genomic DNA and detected in fingernails. Methods: Nails from patients with chronic HBV infection were investigated. A total of 60 patients (male/female = 20/40, age range from 2 years to 59 years, median 15 years) were included in this study. The viral DNA levels of herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), varicella-zoster virus (VZV), Epstein‒Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV-6), human herpes virus 7 (HHV-7), and HBV in nails were measured with real-time PCR. Viral DNA integration into host genomic DNA was analyzed by capture-based next-generation sequencing (NGS). Moreover, virus/host chimeric sequences, which were detected by capture-based NGS, were confirmed by Sanger sequencing. Results: Of the 60 patients, 37 (62%) were positive for nail HBV DNA. All 60 patients were negative for nail HSV-1, HSV-2, VZV, CMV, EBV, or HHV-6 DNA. However, three patients were positive for nail HHV-7 DNA. All three nail HHV-7-positive patients were also positive for nail HBV DNA. The three nail samples that were positive for both HBV and HHV-7 DNA were used for viral integration analysis by capture-based NGS. One of the three nail samples showed HBV/host chimeric sequences. In addition, all three nail samples showed HHV-7/host chimeric sequences. However, these viral integration breakpoints were not confirmed by Sanger sequencing. Conclusions: Viral integrations were detected in nails by capture-based NGS. However, Sanger sequencing did not confirm any virus/host chimeric sequences. This study could not show reliable evidence of viral integration in nails.

The prevalence and predictive factors of nocturnal polyuria in Japanese patients with nocturia: a multicentral retrospective cohort study.

The aims of this study were to determine the prevalence and predictors of nocturnal polyuria (NP) in Japanese patients. This multicentral, observational study enrolled patients with the chief complaint of nocturia at 17 Japanese institutions between January 2018 and December 2022. The frequency of daily voiding and volume of urination were evaluated using bladder diaries. NP was diagnosed in patients with an NP index of > 33%. The primary endpoint was NP prevalence in patients with nocturia. The secondary endpoints were the prevalence of NP according to sex and age and the identification of factors predicting NP. This study analyzed 875 eligible patients. NP was present in 590 (67.4%) patients, with prevalence rates of 66.6% and 70.0% in men and women, respectively. Age ≥ 78 years, body mass index (BMI) < 23.0 kg/m2, and patients with ischemic heart or cerebrovascular disease were significant predictors of NP (P < 0.001, P < 0.001, P = 0.014, P = 0.016, respectively). This is the first large multicenter study to investigate the prevalence of NP in Japanese patients with nocturia. NP has a prevalence of 67.4%. Significant predictors of NP include age, BMI, and cardiovascular disease.

Introduction of reversible cysteine ligation ability to the biliverdin-binding cyanobacteriochrome photoreceptor.

Cyanobacteriochrome (CBCR) photoreceptors are distantly related to the canonical red/far-red reversible phytochrome photoreceptors. In the case of the CBCRs, only the GAF domain is required for chromophore incorporation and photoconversion. The GAF domains of CBCR are highly diversified into many lineages to sense various colors of light. These CBCR GAF domains are divided into two types: those possessing only the canonical Cys residue and those with both canonical and second Cys residues. The canonical Cys residue stably ligates to the chromophore in both cases. The second Cys residue mostly shows reversible adduct formation with the chromophore during photoconversion for spectral tuning. In this study, we focused on the CBCR GAF domain AnPixJg2_BV4, which possesses only the canonical Cys residue. AnPixJg2_BV4 covalently ligates to the biliverdin (BV) chromophore and shows far-red/orange reversible photoconversion. Because BV is a mammalian intrinsic chromophore, BV-binding molecules are advantageous for in vivo optogenetic and bioimaging tool development. To obtain a better developmental platform molecule, we performed site-saturation random mutagenesis and serendipitously obtained a unique variant molecule that showed far-red/blue reversible photoconversion, in which the Cys residue was introduced near the chromophore. This introduced Cys residue functioned as the second Cys residue that reversibly ligated with the chromophore. Because the position of the introduced Cys residue is distinct from the known second Cys residues, the variant molecule obtained in this study would expand our knowledge about the spectral tuning mechanism of CBCRs and contribute to tool development.

Effect of Lacosamide on Interictal Epileptiform Discharges in Pediatric Patients With Newly Diagnosed Focal Epilepsy.

BACKGROUND: The purpose of this study was to determine the efficacy of lacosamide (LCM) on interictal epileptiform discharges (IEDs) and evaluate the relationships between IEDs and seizure outcome in pediatric patients with focal epilepsy. METHODS: Patient inclusion criteria included (1) newly diagnosed focal epilepsy with unknown etiology; and (2) electroencephalogram recorded twice (before and after starting LCM) under the same conditions. The difference between the highest number of IEDs over five successive minutes (IEDs/5 min) and the location of IEDs was determined. Seizure outcome was evaluated one year after achieving the maintenance dose of LCM. Responders were identified as showing a ≥50% reduction in the pre-LCM seizure frequency. RESULTS: Of 22 patients, 10 showed an increase in IEDs/5 min after starting LCM. The median IEDs/5 min before and after starting LCM was not significantly different, at 1.5 (interquartile range: 0, 31.75) and 10.5 (0, 80.5), respectively. No relationship was identified between the difference in IEDs/5 min and seizure outcome. Patients with multiple regional or diffuse IEDs had significantly poorer seizure outcome compared with patients without those IEDs (P = 0.036 and P = 0.039, respectively). Of 10 patients with single regional IEDs, a tendency of IEDs to disappear was observed between patients with frontal and non-frontal IEDs. CONCLUSION: The effects of LCM on the number of IEDs may be unrelated to seizure outcome. LCM may be ineffective at improving seizure outcomes in patients with multiple regional or diffuse IEDs.

Novel cyanobacteriochrome photoreceptor with the second Cys residue showing atypical orange/blue reversible photoconversion.

Cyanobacteriochromes (CBCRs) are cyanobacterial linear tetrapyrrole-binding photoreceptors distantly related to phytochromes. Only the GAF domain is needed for chromophore incorporation and proper photoconversion of the CBCRs. Most CBCR GAF domains possess the canonical Cys residue stably ligating to the chromophore. DXCF-type CBCR GAF domains also possess a second Cys residue within the DXCF motif. This second Cys residue reversibly ligates to the C10 of the chromophore. The Cys adduct formation is mostly observed for the dark-adapted state but not for the photoproduct state. In this study, we discovered novel CBCR GAF domains with a DXCI motif instead of the DXCF motif. Since these CBCR GAF domains are categorized into two subfamilies (DXCI-1 and DXCI-2), the GAF domains from each subfamily were analyzed. Although the CBCR GAF domain belonging to the DXCI-2 subfamily showed orange/green reversible photoconversion without transient Cys ligation, the CBCR GAF domain belonging to the DXCI-1 subfamily showed reversible photoconversion between an orange-absorbing dark-adapted state and a blue-absorbing photoproduct state. This indicates that the second Cys residue is covalently bound to the C10 of the chromophore in the photoproduct state but not in the dark-adapted state. Since the covalent bond formation in the photoproduct state is atypical, site-directed mutagenesis was conducted to understand the molecular mechanism of this GAF domain. The Ile residue within the DXCI motif may be key for covalent bond formation in the photoproduct state.

Signature of chronic hepatitis B virus infection in nails and hair.

BACKGROUND: Hepatitis B virus (HBV) is detected in extrahepatic tissues of individuals with HBV infection. Whether nails and hair contain HBV has been unknown. METHODS: We examined two patient groups: those with chronic HBV infection alone (n = 71), and those with both chronic HBV and hepatitis delta virus (HDV) infections (n = 15). HBV DNA in the patients' fingernails and hair were measured by real-time PCR. Hepatitis B surface antigen (HBsAg) of fingernails was evaluated by an enzyme immunoassay. HDV RNA in fingernails was measured by real-time PCR. Immunochemical staining was performed on nails. We used chimeric mice with humanized livers to evaluate the infectivity of nails. RESULTS: Of the 71 pairs of HBV-alone nail and hair samples, 70 (99%) nail and 60 (85%) hair samples were positive for ß-actin DNA. Of those 70 nail samples, 65 (93%) were HBV DNA-positive. Of the 60 hair samples, 49 (82%) were HBV DNA-positive. The serum HBV DNA level of the nail HBV DNA-positive patients was significantly higher than that of the nail HBV DNA-negative patients (p < 0.001). The hair HBV DNA-positive patients' serum HBV DNA level was significantly higher compared to the hair HBV DNA-negative patients (p < 0.001). The nail HBV DNA level was significantly higher than the hair HBV DNA level (p < 0.001). The nails and hair HBV DNA levels were correlated (r = 0.325, p < 0.05). A phylogenetic tree analysis of the complete genome sequence of HBV isolated from nails and hair identified the infection source. Of the 64 nail samples, 38 (59%) were HBsAg-positive. All 15 pairs of chronic HBV/HDV infection nail and hair samples were ß-actin DNA-positive. However, nail HBV DNA was detected in two patients (13%). None of the 15 patients were positive for hair HBV DNA. Nail HDV RNA was detected in three patients (20%). Of the 15 patients, eight (53%) were nail HBsAg-positive. HBsAg and hepatitis delta (HD) antigen were detected in the nails by immunochemical staining. Chimeric mice were not infected with PBS containing HBsAg and HBV DNA elucidated from nails. CONCLUSIONS: Nails and hair were the reservoir of HBV DNA. Moreover, nails can contain HBsAg, HDV RNA, and HD antigen.

ACTH for epileptic spasms in Leigh syndrome with SLC19A3 mutation can induce status dystonicus.

Patients with Leigh syndrome (LS) sometimes develop epileptic spasms (ES). ACTH treatment for ES may be effective without serious adverse events in some patients with LS. Status dystonicus is a life-threatening disorder characterized by an acute exacerbation of generalized dystonia and often develops as a triggered event. The underlying pathophysiology of status dystonicus remains unclear. To our knowledge, there has been no reported case of status dystonicus associated with ACTH treatment. Here, we describe the first reported patient with LS, harbouring compound heterozygous mutations in SLC19A3 gene, who developed status dystonicus following initial intramuscular injection of a course of ACTH treatment for ES. Stressors can precipitate acute exacerbation in SLC19A3-related disorders. Interestingly, in this patient, external discomfort stimuli tended to induce transient hypertonia with opisthotonos. This report suggests that attention should be paid to acute exacerbation of generalized dystonia when ACTH treatment for ES is started in patients with LS, who have dystonia tend to exacerbate transiently by external discomfort stimuli.

Efficacy of perampanel in epilepsy patients with autism spectrum disorder.

AIM: The aim of this study was to assess the usefulness of perampanel (PER), and to identify the relationship between behavioral impairments and electroencephalogram (EEG) findings in epilepsy patients with autism spectrum disorder (ASD). METHODS: Participants were ASD patients with epilepsy recruited between June 1, 2016 and June 30, 2018. Inclusion criteria were: seizures refractory to two appropriate antiseizure medications (ASMs); presence of neuropsychological impairments; and ≥12 months of monitoring. PER was administered once daily, starting at a dose of 2 mg/day, increased to 12 mg/day. Seizure/EEG responders were identified as participants showing a >50 % reduction in seizure/interictal epileptiform discharge (IED) frequency (indicated as complete disappearance and response). Behavioral responders were identified as participants with a ≥50 % reduction in scores of the Japanese manuals for the Aberrant Behavior Checklist (ABC-J). RESULTS: Eleven (64.7 %) of 17 patients were considered to be both seizure and EEG responders. Five (45.5 %) of these 11 patients with seizure/EEG response were considered as behavioral responders. Mean ABC-J scores were significantly decreased at 12 months after PER administration (p = 0.0002). A correlation between decreased IED frequency and ABC-J score was evident in frontal IEDs, but not in non-frontal IEDs. Participants presenting with frontal IEDs showed a significantly higher correlation between seizures/EEG and behavioral improvements (p = 0.023). Moreover, 2 of 6 patients without seizure/EEG improvement were considered as behavioral responders. No patients discontinued PER. CONCLUSIONS: The results from this study suggest the utility of PER treatment in reducing clinical seizures and IEDs for ASD patients with intractable epilepsy, at least in some patients. Moreover, the present results also indicate the usefulness of PER in improving neuropsychiatric impairments, including behavioral disturbances in ASD related to improvement of clinical seizures/frontal IEDs, but also unrelated to seizure/EEG improvement in at least some ASD patients.

The Cruciality of Single Amino Acid Replacement for the Spectral Tuning of Biliverdin-Binding Cyanobacteriochromes.

Cyanobacteriochromes (CBCRs), which are known as linear tetrapyrrole-binding photoreceptors, to date can only be detected from cyanobacteria. They can perceive light only in a small unit, which is categorized into various lineages in correlation with their spectral and structural characteristics. Recently, we have succeeded in identifying specific molecules, which can incorporate mammalian intrinsic biliverdin (BV), from the expanded red/green (XRG) CBCR lineage and in converting BV-rejective molecules into BV-acceptable ones with the elucidation of the structural basis. Among the BV-acceptable molecules, AM1_1870g3_BV4 shows a spectral red-shift in comparison with other molecules, while NpF2164g5_BV4 does not show photoconversion but stably shows a near-infrared (NIR) fluorescence. In this study, we found that AM1_1870g3_BV4 had a specific Tyr residue near the d-ring of the chromophore, while others had a highly conserved Leu residue. The replacement of this Tyr residue with Leu in AM1_1870g3_BV4 resulted in a blue-shift of absorption peak. In contrast, reverse replacement in NpF2164g5_BV4 resulted in a red-shift of absorption and fluorescence peaks, which applies to fluorescence bio-imaging in mammalian cells. Notably, the same Tyr/Leu-dependent color-tuning is also observed for the CBCRs belonging to the other lineage, which indicates common molecular mechanisms.

Glucose transporter type 1 deficiency syndrome associated with autoantibodies to glutamate receptors.

BACKGROUND: The clinical spectrum of glucose transporter type 1 deficiency syndrome (GLUT1DS) has broadened, with increasing recognition of a milder phenotype. Antibodies targeting the subunits of glutamate receptors (GluRs), including GluN1, GluN2B, and GluD2, have been detected in various neurological disorders. Anti-GluD2 antibodies in particular may be associated with cerebellar symptoms. CASE REPORT: A 3-year-5-month-old boy with normal development exhibited myoclonus refractory to antiepileptic drugs from one year ago. He developed tremor and ataxia. Cerebrospinal fluid (CSF) revealed fasting-state glucose 50 mg/dl (CSF/blood glucose ratio of 0.50). Single photon emission computed tomography with 123I-iodoamphetamine revealed hypoperfusion in the cerebellum. At age 4 years and 5 months, treatment with intravenous methylprednisolone (IVMP) relieved his symptoms and improved the cerebellar hypoperfusion. However, his symptoms reappeared at age 5 years and 1 month. Treatment with IVMP was repeated, resulting in transient disappearance of symptoms. At age 6 years and 9 months, he was diagnosed with GLUT1DS by genetic analysis, and treatment with modified Atkins diet was started with efficacy. Levels of anti-GluN1, -GluN2B, and -GluD2 antibodies in the serum and CSF were measured 4 times. All antibodies in the CSF were elevated over 2 standard deviations above controls, and the levels fluctuated along with the severity of his symptoms. The level of anti-GluD2 antibodies in CSF declined to the normal range only after starting the modified Atkins diet. CONCLUSION: Treatment with IVMP transiently improved this patient's symptoms. Levels of anti-GluR antibodies may be associated with symptom severity.

Effects of perampanel on secondary bilateral synchrony and behavioral problems in adolescents with epilepsy showing insufficient response with levetiracetam.

PURPOSE: The purpose of this study was to determine the efficacy of perampanel (PER) on secondary bilateral synchrony (SBS) and behavioral problems in adolescents with epilepsy who showed insufficient response to levetiracetam (LEV). METHODS: The primary criterion for patient selection was the presence of SBS. The criteria such as age between 12 and 18 years, seizures refractory to antiseizure medications including LEV, at least four seizures a month, neuropsychological impairments, and at least 12 months of follow-up also had to be fulfilled. Patients were given PER at an initial dose of 2 mg/day, followed by increments of +2 mg/day every 2 weeks. Concomitant medications remained unchanged during evaluation period. Responders for electroencephalogram (EEG) and seizures were identified as showing a ≥50 % reduction from the baseline SBS on EEG and seizure frequency, respectively. Neuropsychological impairments as per the Japanese manuals for the Aberrant Behavior Checklist (ABC-J) were evaluated before and after PER administration. RESULTS: Eight of 14 patients were considered responders for seizures. Among these 8 responders, 6 patients were considered responders for EEG and behavioral problems. Mean ABC-J scores in both EEG non-responders and responders were decreased significantly at 12 months (p < 0.05 and p < 0.05, respectively). ABC-J scores were significantly lower in EEG responders than in EEG non-responders at 12 months (p < 0.01). Moreover, among patients with decreased ABC-J scores, the degree of decrease was larger in EEG responders than in EEG non-responders (p < 0.01). CONCLUSIONS: PER may be useful in reducing SBS on EEG, seizure frequency, and behavioral problems.

Efficacy of tocilizumab for fulminant multiple sclerosis with a tumefactive cervical lesion: A 12-year-old boy.

Fulminant demyelinating disease including acute disseminating encephalitis, multiple sclerosis (MS) variants, and neuromyelitis optica spectrum disorder (NMOSD) are often managed with similar acute treatment such as intravenous methylprednisolone and plasma exchange. On the other hand, long-term management varies. The choice of the drug is based on several factors including the activity and severity of the disease course. Tocilizumab (TCZ), which is a humanized anti-interleukin-6 receptor antibody, is one of the promising therapies for NMOSD because of decreasing the relapse rates and possibly the neurological disability. However, the efficacy of TCZ for MS with tumefactive lesion is unknown. Here, we describe the clinical course of a 12-year-old Japanese boy who was diagnosed with fulminant MS with a tumefactive cervical lesion. Our case was refractory to aggressive immunosuppressive therapies and developed dependent on an intermediate dose of oral prednisolone (PSL) for relapse prevention. His neurological condition worsened with every attempt of tapering the PSL dose. Thus, we started treatment with tocilizumab, which allowed of tapering of the PSL dose without his symptom exacerbations, and effectively improved his Expanded Disability Status Scale score. Our findings may indicate that TCZ is effective for fulminant MS patients with a tumefactive cervical lesion.

Skeletal Muscle Volume and Intramuscular Adipose Tissue Are Prognostic Predictors of Postoperative Complications After Hepatic Resection.

BACKGROUND/AIM: Recently, skeletal muscle quality was important in patients with malignant tumors to predict the surgical outcome. The relationship between postoperative complications of Clavien-Dindo grade III or more and prognosis in patients who have undergone hepatic resection for hepatic malignancies were investigated. PATIENTS AND METHODS: Patient data were retrospectively collected for 146 consecutive patients who underwent curative hepatic resection in the Department of Hepatobiliary and Pancreatic Surgery, Gunma University, Japan, for hepatic malignancy. The patients were assigned to two groups according to the presence of postoperative complications. The clinicopathological and surgical outcomes were analyzed. Skeletal muscle area (SMA) and intramuscular adipose tissue content (IMAC) were also evaluated. RESULTS: No hospital deaths occurred. Postoperative complications were identified in 12 patients (8.2%). Univariate and multivariate analyses revealed that the independent risk factors for postoperative complications were hemodialysis, psychiatric disorder, high CONUT (controlling nutritional status) score and patients both with low SMA and high IMAC. CONCLUSION: Intensive surgical care is necessary for high-risk patients with hemodialysis, psychiatric disorder, high CONUT count and/or low skeletal muscle quality to reduce postoperative complication.

Photonic analog-to-digital conversion using a red frequency chirp in a semiconductor optical amplifier.

A photonic analog-to-digital conversion (PADC) based on intensity-to-frequency conversion using a frequency chirp in a semiconductor optical amplifier (SOA) is proposed. The presented PADC has a simple scheme whereby optical quantization is achieved using a single SOA with multiple rectangular bandpass filters placed in parallel. In this Letter, we successfully achieve 10 GSamples/s, eight-level optical quantization using a quantum-dot SOA. The PADC also has much lower input signal pulse power requirements for optical quantization, compared with conventional PADCs.

Computed tomography attenuation values of ascites are helpful to predict perforation site.

AIM: To evaluate the effect of computed tomography (CT) attenuation values of ascites on gastrointestinal (GI) perforation site prediction. METHODS: The CT attenuation values of the ascites from 51 patients with GI perforations were measured by volume rendering to calculate the mean values. The effect of the CT attenuation values of the ascites on perforation site prediction and postoperative complications was evaluated. RESULTS: Of 24 patients with colorectal perforations, the CT attenuation values of ascites were significantly higher than those in patients with perforations at other sites [22.5 Hounsfield units (HU) vs 16.5 HU, respectively, P = 0.006]. Colorectal perforation was significantly associated with postoperative complications (P = 0.038). The prediction rate of colorectal perforation using attenuation values as an auxiliary diagnosis improved by 9.8% compared to that of CT findings alone (92.2% vs 82.4%). CONCLUSION: The CT attenuation values of ascites could facilitate the prediction of perforation sites and postoperative complications in GI perforations, particularly in cases in which the perforation sites are difficult to predict by CT findings alone.

Spontaneous rupture of aneurysms of the ovarian artery at times remote from pregnancy.

Spontaneous rupture of an aneurysm of the ovarian artery is usually considered a rare complication of pregnancy and the puerperium. However, we observed this emergent condition in a 51-year-old postmenopausal woman. We report here our experiences and consider lessons about diagnosis and management that can be drawn from this case and 5 other published cases in multiparous middle-aged women. These lessons include application of contrast-enhanced computed tomography to focus emergent care, surgical intervention, and association with systemic inflammatory response syndrome. We also consider how the cases might shed new light on the pathogenesis and evolution of this condition.

Diagnostic challenge: intraductal neoplasms of the pancreatobiliary system.

To help pathologists avoid misdiagnosis of intraductal neoplasms arising from the pancreatobiliary system, we report two cases that illustrate diagnostic pitfalls. The first is of a 66-year-old man who complained of appetite loss. An early examination led to a diagnosis of intraductal papillary mucinous neoplasm. Macroscopically, a multilocular cyst without visible mucin was identified. Histologically, the compartments consisted of complex fusion of tubular glands surrounded by dilated pancreatic duct. The neoplasm resembled an acinar cell cystadenocarcinoma. However, the neoplastic cells were negative for trypsin. Thus, the final histopathologic diagnosis was an unusual cystic variant of intraductal tubulopapillary neoplasm (ITPN) of the pancreas. The second case is of a 71-year-old man who complained of right upper quadrant pain. Although bile duct stone was suspected, a polypoid nodule was extracted. Histologically, the nodule was composed of tubular glands, with some complex fusion and focal dysplasia, consistent with carcinoma. In addition, lack of MUC-5AC expression led to an initial impression of ITPN of the bile duct. However, the neoplasm showed dysplastic cells based on the columnar cells resembling pyloric glands, indicating the sequential progression. Thus, the final histopathological diagnosis was intraductal papillary neoplasm of the bile duct with high-grade intraepithelial neoplasia. Because phenotypic variants of intraductal neoplasms of the pancreatobiliary system exist, ITPN and ITPN-mimicking tumor must be carefully differentiated from other intraductal neoplasms.

[FOLFIRI with bevacizumab chemotherapy for a patient with recurrence of rectal cancer under haemodialysis for chronic renal failure].

As pharmacokinetics in patients undergoing haemodialysis is different from patients with normal renal function, it remains unclear whether chemotherapy can be performed safely for patients with haemodialysis as well as those who have normal renal function. Here, we report a case with recurrence of rectal cancer who received FOLFIRI with bevacizumab chemotherapy under haemodialysis, and obtained good tumor control. A 47-year-old woman had undergone haemodialysis for 10 years due to chronic renal failure. At 45 years of age, she received abdominoperineal resection due to rectal cancer (pStage II). Four months after the surgery, liver metastasis was found, for which partial resection of the liver and adjuvant chemotherapy [UFT (400 mg/body)/UZEL (75 mg/body)] were performed. Eighteen months after the liver resection, multiple lung metastases were found. Therefore, intensive chemotherapy using FOLFIRI (CPT-11: 90 mg/m2) with bevacizumab (2.5 mg/m2) was performed. Severe neutropenia (grade 3, 4), but not non-hematologic adverse events such as diarrhea and bevacizumab-specific adverse events, was observed. As she did not recover easily from neutropenia in spite of treatment with G-CSF, a dose reduction of the FOLFIRI regimen was gradually performed. Although chemotherapy was conducted approximately monthly, the tumor response reflected a stable disease 8 months after 8 courses of chemotherapy. We suggest that it is important to investigate the pharmacokinetics of toxic agents such as CPT-11, (SN38) for dose modification, and for the safe and continuous chemotherapy of patients receiving haemodialysis.