Patchy and widespread distribution of bacterial translation arrest peptides associated with the protein localization machinery.

Regulatory arrest peptides interact with specific residues on bacterial ribosomes and arrest their own translation. Here, we analyse over 30,000 bacterial genome sequences to identify additional Sec/YidC-related arrest peptides, followed by in vivo and in vitro analyses. We find that Sec/YidC-related arrest peptides show patchy, but widespread, phylogenetic distribution throughout the bacterial domain. Several of the identified peptides contain distinct conserved sequences near the C-termini, but are still able to efficiently stall bacterial ribosomes in vitro and in vivo. In addition, we identify many arrest peptides that share an R-A-P-P-like sequence, suggesting that this sequence might serve as a common evolutionary seed to overcome ribosomal structural differences across species.

The effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically-monitored mouse model of sepsis.

Sepsis, a life-threatening organ dysfunction, results from dysregulated host responses to infection and still has a high incidence and mortality. Although administration of vasopressors to treat septic shock is standard of care, the benefits are not well established. We evaluated the effect of continuous intravenous norepinephrine infusion in a septic cecal ligation and puncture (CLP) mouse model, evaluating systemic hemodynamics and body temperature post-hoc. CLP surgery significantly decreased mean arterial blood pressure (MAP), heart rate, and body temperature within six hours. Continuous norepinephrine infusion (NE+, n = 12) started at the time of CLP surgery significantly increased MAP at 24 and 30 hours and heart rate at 6, 18, 24, and 30 hours after CLP vs CLP alone (NE-, n = 12). However, addition of norepinephrine did not improve survival rate (NE+ n = 34, NE- n = 31). Early (6 hours or earlier, when the animal became visibly sick) MAP did not predict 7-day mortality. However, heart rates at 3 and at 6 hours after CLP/norepinephrine (NE+) were highly predictive of mortality, as also been found in one clinical study. We conclude that limited hemodynamic support can be provided in a mouse sepsis model. We propose that heart rate can be used to stratify severity of illness in rodent preclinical studies of sepsis therapeutics.

Cell-free DNA beyond a biomarker for rejection: Biological trigger of tissue injury and potential therapeutics.

Cell-free DNA, measured as donor-derived cell-free DNA is developed as a non-specific biomarker for allograft injury and transplant rejection. However, cell-free DNA characteristics are more specific, its fragment length, nucleotide content, and composition, as well as the tissue source of origin, are intrinsically linked to the underlying disease pathogenesis, showing distinct features in acute cellular rejection and antibody-mediated rejection for example. Further, cell-free DNA and cell-free mitochondrial DNA can directly trigger tissue injury as damage-associated molecular patterns through three major intracellular receptors, toll-like receptor 9 , cyclic guanosine monophosphate-adenosine monophosphate synthase, and inflammasomes (i.e., absent in melanoma 2: AIM2). Therefore, in addition to its role as a non-specific marker for allograft injury, cell-free DNA analysis may be used to phenotype transplant rejection, and to non-invasively point the underlying molecular mechanisms with allograft injury. Novel treatment approaches targeting these cell-free DNA pathways may be useful to treat transplant rejection and prevent end-organ dysfunction. In this review, we discuss the link between cell-free DNA characteristics and disease, the role of cell-free DNA as a damage-associated molecular pattern, and novel therapeutics targeting these cell-free DNA molecular pathways and their potential utility to treat transplant rejection.

Cell-free DNA maps COVID-19 tissue injury and risk of death and can cause tissue injury.

INTRODUCTIONThe clinical course of coronavirus 2019 (COVID-19) is heterogeneous, ranging from mild to severe multiorgan failure and death. In this study, we analyzed cell-free DNA (cfDNA) as a biomarker of injury to define the sources of tissue injury that contribute to such different trajectories.METHODSWe conducted a multicenter prospective cohort study to enroll patients with COVID-19 and collect plasma samples. Plasma cfDNA was subject to bisulfite sequencing. A library of tissue-specific DNA methylation signatures was used to analyze sequence reads to quantitate cfDNA from different tissue types. We then determined the correlation of tissue-specific cfDNA measures to COVID-19 outcomes. Similar analyses were performed for healthy controls and a comparator group of patients with respiratory syncytial virus and influenza.RESULTSWe found markedly elevated levels and divergent tissue sources of cfDNA in COVID-19 patients compared with patients who had influenza and/or respiratory syncytial virus and with healthy controls. The major sources of cfDNA in COVID-19 were hematopoietic cells, vascular endothelium, hepatocytes, adipocytes, kidney, heart, and lung. cfDNA levels positively correlated with COVID-19 disease severity, C-reactive protein, and D-dimer. cfDNA profile at admission identified patients who subsequently required intensive care or died during hospitalization. Furthermore, the increased cfDNA in COVID-19 patients generated excessive mitochondrial ROS (mtROS) in renal tubular cells in a concentration-dependent manner. This mtROS production was inhibited by a TLR9-specific antagonist.CONCLUSIONcfDNA maps tissue injury that predicts COVID-19 outcomes and may mechanistically propagate COVID-19-induced tissue injury.FUNDINGIntramural Targeted Anti-COVID-19 grant, NIH.

Monoclonal immunoglobulin G1 κ-type atypical antiglomerular basement membrane disease accompanied by necrotizing glomerulonephritis
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INTRODUCTION: Patients without detectable serum antiglomerular basement membrane (GBM) antibodies but with GBM staining for immunoglobulins (Ig), absence of a crescentic phenotype, mild renal insufficiency, and absence of pulmonary hemorrhage have atypical anti-GBM diseases. We report the case of a 64-year-old man with slowly progressive glomerulonephritis. CASE HISTORY: A 64-year-old Peruvian man presented with persistent microscopic hematuria, proteinuria of 2.1 g/g creatinine (Cr), serum Cr 1.00 mg/dL, and C-reactive protein 0.80 mg/dL. Renal biopsy revealed necrotizing glomerulonephritis with 39% cellular crescent formation and diffuse segmental endocapillary proliferation. He had linear staining of monoclonal IgG1-κ in the capillary walls but no detectable serum anti-GBM antibodies. Because renal dysfunction was slowly progressing, steroid monotherapy was initiated, and serum Cr level decreased from 1.48 to 1.13 mg/dL. However, serum Cr increased again to 1.35 mg/dL owing to active glomerular damage with crescent formation and endocapillary proliferation, confirmed by the second renal biopsy at 9 months after therapy. Renal function improved after cyclophosphamide therapy. CONCLUSION: We described an atypical variant of anti-GBM disease due to monoclonal IgG1-κ. Unlike usual atypical anti-GBM disease cases, we observed crescent formation in our patient. Further investigations are needed to identify the cause of nondetectable serum anti-GBM antibodies and to describe the causal relationships between clinicopathological features and the pattern of IgG subclass and light chain in atypical anti-GBM disease.

A case report of thin basement membrane nephropathy accompanied by sporadic glomerulocystic kidney disease.

BACKGROUND: Thin basement membrane nephropathy (TBMN) is a relatively common disease. Patients typically present with isolated hematuria, which has a good renal prognosis. In contrast, glomerulocystic kidney disease (GCKD) is a rare disease, associated with slow progressive renal dysfunction. To our knowledge, co-occurring diagnosis of TBMN with GCKD has not been reported previously. CASE PRESENTATION: A 30-year old woman was admitted to our hospital for evaluation of hematuria and renal insufficiency. Upon examination, her urinary protein level was 40 mg/day and occult blood in her urine was 2+. The patient's urinary dysmorphic red blood cell sediment was 30-49/high power field. In contrast, her serum creatinine levels increased from 0.57 mg/dl to 0.86 mg/dl during the previous 2-years, without special events. She suffered from far-sightedness and astigmatism beginning at birth; She had no family history of renal disease. Renal biopsy demonstrated cystic dilatation of the Bowman's capsule and atrophy of the glomerular tuft. The glomerular basement membrane (GBM) was thin, with an average thickness of 191 nm. Next-generation sequencing was used to evaluate for mutations in COL4A3 and COL4A4, associated with TBMN, and UMOD, MUC1, and SEC61A1, associated with hereditary GCKD. No pathogenic mutations were identified. We thus diagnosed the patient with TBMN coexistent with sporadic GCKD. CONCLUSION: We report the patient diagnosed with TBMN accompanied by sporadic GCKD, based on renal biopsy and genetic testing. Because it is possible that other diseases, such as GCKD, can coexist with TBMN, it is important to consider renal biopsy.

Risk factors for local recurrence and appropriate surveillance interval after endoscopic resection.

BACKGROUND: Risk factors for local recurrence after polypectomy, endoscopic mucosal resection (EMR), and endoscopic submucosal dissection (ESD) have not been identified. Additionally, the appropriate interval for endoscopic surveillance of colorectal tumors at high-risk of local recurrence has not been established. AIM: To clarify the clinicopathological characteristics of recurrent lesions after endoscopic colorectal tumor resection and determine the appropriate interval. METHODS: Three hundred and sixty patients (1412 colorectal tumors) who underwent polypectomy, EMR, or ESD and received endoscopic surveillance subsequently for more than one year to detect local recurrence were enrolled in this study. The clinicopathological factors associated with local recurrence were determined via univariate and multivariate analyses. RESULTS: Local recurrence was observed in 31 of 360 (8.6%) patients [31 of 1412 (2.2%) lesions] after colorectal tumor resection. Piecemeal resection, tumor size of more than 2 cm, and the presence of villous components were associated with colorectal tumor recurrence after endoscopic resection. Of these three factors, the piecemeal resection procedure was identified as an independent risk factor for recurrence. Colorectal tumors resected into more than five pieces were associated with a high risk of recurrence since the average period from resection to recurrence in these cases was approximately 3 mo. The period to recurrence in cases resected into more than 5 pieces was much shorter than that in those resected into less than 4 pieces (3.8 ± 1.9 mo vs 7.9 ± 5.0 mo, P < 0.05). CONCLUSION: Local recurrence of endoscopically treated colorectal tumors depends upon the outcome of first endoscopic procedure. Piecemeal resection was the only significant risk factor associated with local recurrence after endoscopic resection.

A Rare Case of Lupus Nephritis Presenting as Thrombotic Microangiopathy with Diffuse Pseudotubulization Possibly Caused by Atypical Hemolytic Uremic Syndrome.

A 31-year-old woman was admitted to our hospital for thrombotic microangiopathy (TMA). She was diagnosed with systemic lupus erythematosus (SLE) and class V lupus nephritis. She had no aggravated SLE activity, Shiga toxin positivity, ADAMTS13 abnormality, or other causes of secondary TMA. Plasma exchange partially improved TMA, and eculizumab was introduced for suspected atypical hemolytic uremic syndrome (aHUS), as eculizumab was effective in suppressing the TMA activity. A kidney biopsy revealed diffusely organized crescents (pseudotubulization) with glomerular and arteriolar endothelial injury and subepithelial immune deposits. Thus, this was a rare case of lupus nephritis presenting as TMA with pseudotubulization possibly caused by aHUS.

Risk Factors for Complications in Expander-Based Breast Reconstruction: Multivariate Analysis in Asian Patients.

BACKGROUND: There have been many studies examining risk factors for complications in expander-based breast reconstruction after mastectomy, and some patient factors have been identified as risk factors. However, most of the previous studies were based on Caucasian patients. METHODS: Asian patients who had a tissue expander placed for immediate breast reconstruction between January 2006 and December 2015 (363 patients and 371 expanders) were analyzed retrospectively. Univariate and multivariate analyses were performed to elucidate risk factors for complications. RESULTS: The rate of skin necrosis was significantly higher in nipple-sparing mastectomy than in other types of mastectomies (12 patients among 107 patients, P = 0.001). The weight of the resected specimen was significantly higher in the group with complications than in the group without complications (444 g compared with 363 g, P = 0.027). Other factors (age, body mass index, smoking, expander type, preoperative chemotherapy, axillary dissection) had no significant effect on complications. Multivariate analysis with a logistic regression showed that a large breast (over 500 g) was the only significant risk factor for complications, with an odds ratio of 3.20 and a 95% confidence interval of 1.33-7.54 (P = 0.010). CONCLUSION: In this series of Asian patients, breast size, rather than body mass index, is the most important predictor for complications in expander-based breast reconstruction.

Focal segmental glomerulosclerosis associated with cutaneous and systemic plasmacytosis.

Cutaneous and systemic plasmacytosis (CSP) is a rare lymphoproliferative disorder that mainly affects middle-aged Asian individuals. Although Castleman disease is often complicated with various renal involvements, glomerulonephritis associated with CSP, which is considered as a variant of Castleman disease, is rare. This report presents the case of a 41-year-old Japanese man with nephrotic syndrome associated with CSP. Renal biopsy findings showed focal segmental glomerulosclerosis (FSGS) and diffusely mild segmental mesangial proliferation. Plasma cell infiltration in the interstitium was not observed. Electron microscopic findings showed diffuse foot process effacement, localized involvement of subendothelial space widening with amorphous materials, and endothelial cell swelling. Lymph node biopsy findings denied Castleman disease. His skin regions and proteinuria were successfully treated with prednisolone and cyclosporine. The causal relationship between CSP and FSGS is unknown. However, increased serum levels of IL-6 and VEGF and decreased VEGF expression in the podocyte may contribute to renal lesions in patients with CSP. To our best knowledge, this is the first case of a patient with FSGS associated with CSP.

Membranous Nephropathy with an Enhanced Granular Expression of Thrombospondin Type-1 Domain-containing 7A in a Pregnant Woman.

A 30-year-old woman with proteinuria first noted at 26 weeks of gestation was admitted to undergo further evaluation. A renal biopsy revealed membranous nephropathy (MN). There was no evidence of any secondary MN. Prednisolone was initiated 6 months after delivery. Four months later, her urine protein became negative. Enhanced granular staining for thrombospondin type-1 domain-containing 7A (THSD7A) in the glomeruli was retrospectively detected in a biopsy specimen. A literature review revealed that 60% of cases of THSD7A-related MN occurred in women of childbearing age. Therefore, THSD7A-related MN should be considered in female patients presenting with idiopathic MN in childbearing age.

Tubulointerstitial Nephritis Caused by Peritubular Capillaritis Accompanied by Cryoglobulinemia.

A 73-year-old man with fever, renal insufficiency, and purpura was referred to our hospital to be evaluated for renal insufficiency. Renal biopsy revealed acute and chronic tubulointerstitial nephritis with no laboratory findings of sarcoidosis or connective tissue disease. Low C4 levels and elevation of rheumatoid factors suggested cryoglobulinemia, which was confirmed with quantitative analysis. CD34 staining of kidney tissue revealed peritubular capillaritis. Antineutrophil cytoplasmic antibodies were negative. The etiology of peritubular capillaritis was not clear in our patient; however, it might be associated with cryoglobulinemia because we cannot find any other diseases that could have induced the peritubular capillaritis.

Primary leiomyosarcoma of the colon.

Primary leiomyosarcomas of the gastrointestinal (GI) tract are extremely rare and highly aggressive neoplasms, and only a small number of true cases have been reported since the concept of GI stromal tumors was established. Here, we report a case of a primary leiomyosarcoma of the transverse colon. A 46-year-old Japanese male with a large mass in the right upper abdomen was admitted to our hospital. Computed tomography and magnetic resonance imaging revealed long segments of wall thickening of the transverse colon with large consecutive tumors measuring 12 cm in diameter. A projecting irregular mass with marked mucosal necrosis was found on colonoscopy. Pathological examination revealed a spindle cell tumor growing circumferentially and transmurally to replace the muscularis propria in the transverse colon. The spindle cells were positive for smooth muscle actin, and negative for KIT, CD34, DOG-1, and S-100 protein. The patient has shown repeat recurrence in spite of sufficient surgical excision being promptly performed.

[Metastatic tumor of the spermatic cord from gastric cancer: a case report].

A 66-year-old man presented with a painless swelling of left scrotal contents. We performed left inguinal orchiectomy and left inguinal lymphnode dissection. Histopathological examination revealed spermatic cord metastases from gastric carcinoma. We collected 44 cases of metastatic tumor of the spermatic cord from gastric cancer in the Japanese literature.

Development of the Japanese version of the Minneapolis-Manchester Quality of Life Survey of Health - Adolescent Form (MMQL-AF) and investigation of its reliability and validity.

BACKGROUND: There are very few reliable and valid measures in Japan assessing health-related quality of life (HRQOL) in children with cancer. The present study aimed to develop a Japanese version of the Minneapolis-Manchester Quality of Life Survey of Health Adolescent Form (MMQL-AF), which is a measure for assessing the HRQOL of childhood cancer survivors, and investigate its reliability and validity. METHODS: Participants were 141 children with cancer who had been off therapy for more than one year and 183 healthy controls. The reliability and internal consistency of the measure were assessed through test-retest methods using Cronbach's coefficient alpha and intra-class correlation coefficients (ICCs). For validation of the measure, factorial validity, concurrent validity using the Japanese version of PedsQL 4.0 Generic Core Scales (PedsQL-J), and discriminant validity using comparisons between children with cancer and healthy controls were investigated. RESULTS: Of the 46 items in the original version, 44 items were determined to comprise the Japanese version of the MMQL-AF. Cronbach's coefficient alphas for each subscale were high ranging from 0.83 to 0.89. Test-retest reliability ranged between ICC 0.79 to 0.96. Investigation of concurrent validity using the PedsQL-J demonstrated strong correlations in physical functions and moderate correlations for other factors. A significant difference was observed between children with cancer and healthy controls. CONCLUSIONS: Thus, the Japanese version of the MMQL-AF served as a self-evaluation questionnaire that allowed for practical, comprehensive, and multidimensional measurement of HRQOL specific to childhood cancer survivors.

CD34 expression in noncancerous liver tissue predicts multicentric recurrence of hepatocellular carcinoma.

BACKGROUND: Metachronous multicentric recurrence of hepatocellular carcinoma (HCC) is a common cause of morbidity and mortality following curative surgical resection. Clinical and laboratory predictors of these processes can markedly aid in managing these patients. Capillarization of hepatic sinusoids is also a well-known phenomenon in many liver diseases, especially in neoplastic liver diseases. Here, we investigated the clinical features, fibrosis scores and distribution of CD34 in noncancerous hepatic tissues of postresection patients with and without multicentric recurrence. METHODS: Eighteen patients with multicentric recurrence of HCC diagnosed by histological examination of repeated hepatectomy specimens and 72 HCC patients with more than 5-year disease-free survival postresection participated in the study. We compared the clinicopathological features of these two groups. We examined noncancerous hepatic tissues for iron deposition by Prussian blue staining and computed the CD34-labeling index (LI) through immunohistochemistry using anti-CD34 antibody. RESULTS: CD34-LI was significantly higher in the multicentric recurrence group (p < 0.001) and staging scores of fibrosis were also significantly higher in the recurrence group (p = 0.035). A high histological activity grade (p = 0.057) and a high alanine aminotransferase level (p = 0.060) were also associated with recurrence. There were no significant differences between the two groups in age, sex, hepatitis B virus surface antigen and anti-hepatitis C virus antibody levels, or grade of iron deposition. On multivariate analysis, high CD34-LI was the only independent risk factor (p = 0.001) for metachronous multicentric recurrence. CONCLUSION: CD34 expression in the capillaries and sinusoids of noncancerous hepatic tissue is a risk factor for multicentric recurrence of HCC. Histologic assessment of hepatic tissue with CD34 immunohistochemistry might be useful for the prognostic evaluation of HCC patients after surgery.

Calcitriol-induced hypercalcemia in a patient with granulomatous mycosis fungoides and end-stage renal disease.

An 86-year-old man, diagnosed as having mycosis fungoides in May 2008 and treated with repeated radiation therapy, was admitted to our hospital for initiation of hemodialysis due to end-stage renal disease (ESRD) in April 2012. On admission, his corrected serum calcium level was 9.3 mg/dL, and his intact parathyroid hormone level was 121.9 pg/mL (normal range 13.9-78.5 pg/mL), indicating secondary hyperparathyroidism due to ESRD. After starting hemodialysis, urinary volume diminished rapidly. The serum calcium level increased (12.7 mg/dL), and the intact parathyroid hormone level was suppressed (< 5 pg/mL), while the 1,25-dihydroxyvitamin D3 (calcitriol) level increased (114 pg/mL, normal range: 20.0-60.0 pg/mL) in June 2012. The possibilities of sarcoidosis and tuberculosis were ruled out. Skin biopsies from tumorous lesions revealed a diagnosis of granulomatous mycosis fungoides. The serum soluble interleukin-2 receptor levels and the degrees of skin lesions went in parallel with the increased serum calcium and calcitriol levels. Therefore, the patient was diagnosed as having calcitriol-induced hypercalcemia possibly associated with granulomatous mycosis fungoides. Granulomatous mycosis fungoides is rare, and its association with calcitriol-induced hypercalcemia has not been reported. Careful attention to calcium metabolism is needed in patients with granulomatous mycosis fungoides, especially in patients with ESRD.

Effect of prolonged ischaemic time on muscular atrophy and regenerating nerve fibres in transplantation of the rat hind limb.

Our aim was to test the influence of cold ischaemia on replanted limbs, focusing on muscular atrophy and neurological recovery. Inbred wild-type and green fluorescent protein (GFP) transgenic (Tg) Lewis rats aged 8-10 weeks were used. The amputated limbs were transplanted at several cold ischaemic times (0, 1, 8, 12, 24, 48, and 72 hours). An arterial ischaemic model and a denervation model were used as controls. To study nerve regeneration, a GFP limb was transplanted on to the syngenic wild Lewis rat. These animals were evaluated histologically, electrophysiologically, and immunohistochemically. The longer the ischaemic time, the more evident was atrophy of the muscles. Electrophysiological investigation showed that the latency at 3 weeks was longer in the transplantation models than in the normal controls, particularly in the longer ischaemia group. Larger numbers of migrating Schwann cells were seen in the group with no delay than in the group that had been preserved for 12 hours. Ischaemia after amputation of a limb causes muscle cells to necrose and atrophy, and these changes worsen in proportion to the ischaemic preservation time. A delay in nerve regeneration and incomplete paralysis caused by malregeneration also affect muscular atrophy.

Quantification of tumor vascularity with contrast-enhanced ultrasound for early response of transcatheter arterial chemoembolization for hepatocellular carcinoma: a report of three cases.

Many contrast-enhanced ultrasound (CE-US) studies have been conducted by qualitative analysis of blood flow, such as classification of enhancement pattern. We evaluated early response of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) by quantitative analysis of intratumoral vascularity with CE-US in three patients. Three patients (one man, two women) with HCCs were treated in July 2009. CE-US with perfluorocarbon microbubbles (Sonazoid) and CT were performed serially before and 5 days after TACE. Post-processing enhancement intensity on US was analyzed to determine mean transit time (s), time to peak (s), enhancement peak intensity (dB), and "A" (scaling factor) by ultrasound quantification software after the data were fitted to a gamma variate curve. Mean transit time was prolonged by TACE in all three patients. Mean transit time rates on CE-US were 64.3, 33.8, and 65.6%, respectively, whereas the avascular rates on CT were 59.07, 31.71, and 62.25%, respectively. Mean transit time rates on CE-US approximated avascular rates on CT. Mean transit time rate may quantitatively indicate the early response of HCC to TACE.

Validation of the Japanese version of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module.

BACKGROUND: The PedsQL 3.0 Cancer Module is a widely used instrument to measure pediatric cancer specific health-related quality of life (HRQOL) for children aged 2 to 18 years. We developed the Japanese version of the PedsQL Cancer Module and investigated its reliability and validity among Japanese children and their parents. METHODS: Participants were 212 children with cancer and 253 of their parents. Reliability was determined by internal consistency using Cronbach's coefficient alpha and test-retest reliability using intra-class correlation coefficient (ICC). Validity was assessed through factor validity, convergent and discriminant validity, concurrent validity, and clinical validity. Factor validity was examined by exploratory factor analysis. Convergent and discriminant validity were examined by multitrait scaling analysis. Concurrent validity was assessed using Spearman's correlation coefficients between the Cancer Module and Generic Core Scales, and the comparison of the scores of child self-reports with those of other self-rating depression scales for children. Clinical validity was assessed by comparing the on- and off- treatment scores using Kruskal-Wallis and Mann-Whitney U tests. RESULTS: Cronbach's coefficient alpha was over 0.70 for the total scale and over 0.60 for each subscale by age except for the 'pain and hurt' subscale for children aged 5 to 7 years. For test-retest reliability, the ICC exceeded 0.70 for the total scale for each age. Exploratory factor analysis demonstrated sufficient factorial validity. Multitrait scaling analysis showed high success rates. Strong correlations were found between the reports by children and their parents, and the scores of the Cancer Module and the Generic Core Scales except for 'treatment anxiety' subscales for child reports. The Depression Self-Rating Scale for Children (DSRS-C) scores were significantly correlated with emotional domains and the total score of the cancer module. Children who had been off treatment over 12 months demonstrated significantly higher scores than those on treatment. CONCLUSIONS: The results demonstrate the reliability and validity of the Japanese version of the PedsQL Cancer Module among Japanese children.