Hiroshima Prefectural Hospital

These 62 patients with the Kabuki make-up syndrome (KMS) were collected in a collaborative study among 33 institutions and analyzed clinically, cytogenetically, and epidemiologically to delineate the phenotypic spectrum of KMS and to learn about its cause. Among various manifestations observed, most patients had the following five cardinal manifestations: 1) a peculiar face (100%) characterized by eversion of the lower lateral eyelid; arched eyebrows, with sparse or dispersed lateral one-third; a depressed nasal tip; and prominent ears; 2) skeletal anomalies (92%), including brachydactyly V and a deformed spinal column, with or without sagittal cleft vertebrae; 3) dermatoglyphic abnormalities (93%), including increased digital ulnar loop and hypothenar loop patterns, absence of the digital triradius c and/or d, and presence of fingertip pads; 4) mild to moderate mental retardation (92%); and 5) postnatal growth deficiency (83%). Thus the core of the phenotypic spectrum of KMS is rather narrow and clearly defined. Many other inconsistent anomalies were observed. Important among them were early breast development in infant girls (23%), and congenital heart defects (31%), such as a single ventricle with a common atrium, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of aorta, patent ductus arteriosus, aneurysm of aorta, transposition of great vessels, and right bundle branch block. Of the 62 KMS patients, 58 were Japanese, an indication that the syndrome is fairly common in Japan. It was estimated that its prevalence in Japanese newborn infants is 1/32,000. All the KMS cases in this study were sporadic, the sex ratio was even, there was no correlation with birth order, the consanguinity rate among the parents was not high, and no incriminated agent was found that was taken by the mothers during early pregnancy. Three of the 62 patients had a Y chromosome abnormality involving a possible common breakpoint (Yp11.2). This could indicate another possibility, i.e., that the KMS gene is on Yp11.2 and that the disease is pseudoautosomal dominant. These findings are compatible with an autosomal dominant disorder in which every patient represents a fresh mutation. The mutation rate was calculated at 15.6 X 10(6).

AIM: To investigate whether the aqueous levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are correlated to the vitreous levels of these substances and to the severity of macular oedema in branch retinal vein occlusion (BRVO). METHODS: Aqueous and vitreous samples were obtained during cataract and vitreous surgery from 24 patients (24 eyes) with macular oedema in BRVO. The VEGF and IL-6 levels in aqueous humour, vitreous fluid, and plasma were determined by enzyme-linked immunosorbent assay. The degree of retinal ischaemia was evaluated in terms of the area of capillary nonperfusion using the Scion Image. The severity of macular oedema was evaluated using the OCT. RESULTS: The aqueous level of VEGF was significantly correlated with the vitreous level of VEGF (P<0.0001). Vitreous levels of VEGF and IL-6 were significantly correlated with the nonperfusion area of BRVO (P<0.0001, P=0.0061, respectively), as were the aqueous levels of VEGF and IL-6 (P<0.0001, P=0.0267, respectively). Furthermore, the vitreous levels of VEGF and IL-6 and the aqueous level of VEGF were significantly correlated with the severity of macular oedema of BRVO (P=0.0001, P=0.0331, P=0.0272, respectively). CONCLUSION: Our results suggest that the aqueous level of VEGF may reflect its vitreous level. Measurement of the aqueous level of VEGF may be clinically useful to indicate the severity of macular oedema with BRVO.

INTRODUCTION: Fever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness. METHODS: We designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring >48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality. RESULTS: We recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P=0.028, acetaminophen: 2.05, P=0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P=0.15, acetaminophen: 0.58, P=0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU ≥ 39.5°C increased risk of 28-day mortality in non-septic patients (adjusted odds ratio 8.14, P=0.01), but not in septic patients (adjusted odds ratio 0.47, P=0.11) [corrected]. CONCLUSIONS: In non-septic patients, high fever (≥39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00940654.

We identified a novel pathogenicity island in Staphylococcus aureus which contains open reading frames (ORFs) similar to the exfoliative toxin (ET) gene, glutamyl endopeptidase gene, and edin-B gene in tandem and the phage resistance gene, flanked by hsdM, hsdS (restriction and modification system), and IS256. The protein encoded by the ET-like gene showed 40, 59, and 68% amino acid sequence identities with exfoliative toxin A (ETA), exfoliative toxin B (ETB), and Staphylococcus hyicus ETB (ShETB), respectively. When injected into neonatal mice, the recombinant protein derived from the ET-like gene induced exfoliation of the skin with loss of cell-to-cell adhesion in the upper part of the epidermis as observed in histological examinations, just as was found in neonatal mice injected with ETA or ETB. Western blot analysis indicated that the recombinant protein is serologically distinct from ETA and ETB. Therefore, the product encoded by this new ORF is a new ET member produced by S. aureus and is termed ETD. ETD did not induce blisters in 1-day-old chickens. In the skins of mice injected with ETD, cell surface staining of desmoglein 1 (Dsg1), a cadherin type cell-to-cell adhesion molecule in desmosomes, was abolished without affecting that of desmoglein 3 (Dsg3). Furthermore, in vitro incubation of the recombinant extracellular domains of Dsg1 and Dsg3 with the recombinant protein demonstrated that both mouse and human Dsg1, but not Dsg3, were directly cleaved in a dose-dependent manner. These results demonstrate that ETD and ETA induce blister formation by identical pathophysiological mechanisms. Clinical strains positive for edin-B were suggested to be clonally associated, and all edin-B-positive strains tested were positive for etd. Among 18 etd-positive strains, 12 produced ETD extracellularly. Interestingly, these strains are mainly isolated from other sources of infections and not from patients with bullous impetigo or staphylococcal scalded-skin syndrome. This strongly suggests that ETD might play a pathogenic role in a broader spectrum of bacterial infections than previously considered.

BACKGROUND AND PURPOSE: Previously we have studied the relationship between senile depression and silent cerebral infarctions (SCIs). The goal of this study was to clarify the relationship between late-onset mania and SCIs using MR imaging. METHODS: Twenty manic patients who developed a bipolar disorder after 50 years of age (late-onset mania) were selected prospectively. These patients were compared with 20 age- and sex-matched patients who developed an affective disorder while younger than 50 years of age (early-onset affective disorder) and with 20 patients who developed major depression after 50 years of age (late-onset major depression). Patients with focal neurological symptoms were excluded from the study. All patients underwent MR imaging to assess the incidence of SCIs. Patients diagnosed with SCIs were subclassified according to whether the infarction type was perforating, cortical, or mixed. RESULTS: The incidence of SCIs in patients with late-onset mania was 65.0%; this incidence was significantly higher than that of patients with early-onset affective disorders (P < .05). The incidence of the mixed type of SCI was 50.0% in patients with late-onset mania; this was significantly higher than that in patients with late-onset major depression (P < .05). CONCLUSIONS: Our findings suggest that approximately half of the cases of late-onset mania might be secondary mania related to SCIs. Because the mixed type of SCI is more prevalent in the patients with late-onset mania than in those with late-onset major depression, mania may be associated with the larger areas of brain damage and hence may be a more serious form of affective illness than major depression.

PURPOSE It remains controversial whether primary tumor resection (PTR) before chemotherapy improves survival in patients with colorectal cancer (CRC) with asymptomatic primary tumor and synchronous unresectable metastases. PATIENTS AND METHODS This randomized phase III study investigated the superiority of PTR followed by chemotherapy versus chemotherapy alone in relation to overall survival (OS) in patients with unresectable stage IV asymptomatic CRC and three or fewer unresectable metastatic diseases confined to the liver, lungs, distant lymph nodes, or peritoneum. Chemotherapy regimens of either mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab were decided before study entry. The primary end point was OS, which was analyzed by intention-to-treat. RESULTS Between June 2012 and September 2019, a total of 165 patients were randomly assigned to either chemotherapy alone (84 patients) or PTR plus chemotherapy (81 patients). When the first interim analysis was performed in September 2019 with 50% (114/227) of the expected events observed among 160 patients at the data cutoff date of June 5, 2019, the Data and Safety Monitoring Committee recommended early termination of the trial because of futility. With a median follow-up of 22.0 months, median OS was 25.9 months (95% CI, 19.9 to 31.5) in the PTR plus chemotherapy arm and 26.7 (95% CI, 21.9 to 32.5) in the chemotherapy-alone arm (hazard ratio, 1.10; 95% CI, 0.76 to 1.59; one-sided P = .69). Three postoperative deaths occurred in the PTR plus chemotherapy arm. CONCLUSION Given that PTR followed by chemotherapy showed no survival benefit over chemotherapy alone, PTR should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases.

PURPOSE This study evaluated the continuous use of trastuzumab beyond progression (TBP) in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. PATIENTS AND METHODS Patients with HER2-positive advanced G/GEJ cancer refractory to first-line chemotherapy with trastuzumab in combination with fluoropyrimidine and platinum were eligible. Patients were randomly assigned to the paclitaxel (80 mg/m 2 , days 1, 8, and 15, every 4 weeks) or paclitaxel with trastuzumab (PT; initially 8 mg/kg followed by 6 mg/kg, every 3 weeks) arms. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate, and safety. Biomarkers such as HER2 expression status in tumor tissue after first-line treatment, HER2 amplification evaluated in serum cell-free DNA, and soluble HER2 levels were analyzed. RESULTS Overall, 91 patients were allocated to the paclitaxel (n = 46) and PT (n = 45) arms. The median PFS in the paclitaxel and PT arms was 3.2 and 3.7 months, respectively (hazard ratio [HR], 0.91; 80% CI, 0.67 to 1.22; P = .33), and the median OS in both arms was 10 months (HR, 1.2; 95% CI, 0.75 to 2.0; P = .20). The overall response rates in the paclitaxel and PT arms were 32% and 33%, respectively ( P = 1.00), and safety was comparable between the 2 arms. On exploratory analyses, HER2 positivity of tumor tissues was lost after first-line chemotherapy in 11 (69%) of 16 patients whose tumor tissues were available, and circulating HER2 DNA amplification was detected in 41 (60%) of 68 patients. However, no biomarkers associated with efficacy of TBP were found. CONCLUSION The TBP strategy failed to improve PFS in patients with HER2-positive advanced G/GEJ cancer, and no beneficial biomarkers were found.

The name Flexibacter maritimus is proposed for a group of 15 bacterial strains isolated from diseased red sea bream (Pagrus major), black sea bream (Acanthopagrus schlegeli), and rock bream (Oplegnathus fasciatus). These bacteria grew in cytophaga medium prepared with seawater but failed to grow in cytophaga medium supplemented with NaCl. The isolates were gram-negative, flexible rods which exhibited gliding motility on wet surfaces. They did not utilize agar, cellulose, or chitin. The mean guanine-plus-cytosine content of the deoxyribonucleic acids of eight selected strains was 31.8 ± 0.4 mol%. Strain R2 (= NCMB 2514) is designated the type strain of the new species.

To identify proteins that could be molecular targets for diagnosis and treatment of hepatitis C virus-related hepatocellular carcinoma (HCV-related HCC), we used a proteomic approach to analyze protein expression in samples of human liver. Twenty-six pairs of tumorous and corresponding nontumorous liver samples from patients with HCV-related HCC and six normal liver samples were analyzed by two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry. One of the numerous spots that showed stronger intensity in tumorous than in nontumorous samples was identified as alpha enolase, a key enzyme in the glycolytic pathway. Expression of this protein increased with tumor dedifferentiation and was significantly higher in poorly differentiated HCC than in well-differentiated HCC. This pattern was reproduced by immunoblot analysis and immunohistochemistry. Expression of alpha enolase also correlated positively with tumor size and venous invasion. These results suggest that alpha enolase is one of the candidates for biomarkers for tumor progression that deserves further investigation in HCV-related HCC.

Background. Recent reports indicate that matrix metalloproteinase-7 (MMP-7) and CC-chemokine ligand 18 (CCL18) are potential disease markers of idiopathic pulmonary fibrosis (IPF). The objective of this study was to perform direct comparisons of these two biomarkers with three well-investigated serum markers of IPF, Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), and SP-D. Methods. The serum levels of MMP-7, CCL18, KL-6, SP-A, and SP-D were evaluated in 65 patients with IPF, 31 patients with bacterial pneumonia, and 101 healthy controls. The prognostic performance of these five biomarkers was evaluated in patients with IPF. Results. The serum levels of MMP-7, KL-6, and SP-D in patients with IPF were significantly elevated compared to those in patients with bacterial pneumonia and in the healthy controls. Multivariate survival analysis showed that serum MMP-7 and KL-6 levels were independent predictors in IPF patients. Moreover, elevated levels of both KL-6 and MMP-7 were associated with poorer survival rates in IPF patients, and the combination of both markers provided the best risk discrimination using the C statistic. Conclusions. The present results indicated that MMP-7 and KL-6 were promising prognostic markers of IPF, and the combination of the two markers might improve survival prediction in patients with IPF.

INTRODUCTION: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. METHODS: The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. RESULTS: Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly correlated with intrathoracic blood volume (r = 0.236, P < 0.01). EVLWI was weakly correlated with the PaO2/FiO2 ratio in the ALI/ARDS and cardiogenic edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95). CONCLUSION: PVPI may be a useful quantitative diagnostic tool for ARDS in patients with hypoxemic respiratory failure and radiographic infiltrates. TRIAL REGISTRATION: UMIN-CTR ID UMIN000003627.

A diagnosis of low-grade fibromyxoid sarcoma (LGFMS) remains problematic because of its bland-looking histologic features that can be potentially confused with other benign or low-grade fibromyxoid lesions. Recent cytogenetic and molecular analyses have shown that most LGFMSs have a characteristic chromosomal abnormality, t(7;16)(q33;p11), resulting in the FUS-CREB3L2 fusion gene. However, such assays have only rarely been used to analyze formalin-fixed, paraffin-embedded tumor samples. In the present study, we conducted a reverse transcription-polymerase chain reaction assay to detect the FUS-CREB3L2 fusion transcripts using formalin-fixed, paraffin-embedded tumor tissue specimens from 16 LGFMSs including 3 cases with giant collagen rosettes. The primers were newly designed to specifically amplify most of the junctional regions of the FUS-CREB3L2 fusion gene transcripts previously reported. The FUS-CREB3L2 fusion gene transcripts were detected in 14/16 (88%) cases of LGFMS. A nucleotide sequence analysis of the PCR products revealed that different portions of the FUS exon 6 or 7 were fused with various sites of the CREB3L2 exon 5, resulting in 12 different nucleotide sequences. We also tested a primer set to detect the FUS-CREB3L1 fusion transcript, which is a rare variant of the gene fusion in LGFMS, although no PCR products were identified in any case. The FUS-CREB3L2 fusion transcripts were not detected in any of the 123 other soft-tissue tumors, including desmoid-type fibromatoses, myxofibrosarcomas, soft-tissue perineuriomas, and congenital or adult fibrosarcomas. These data suggest that our reverse transcription-polymerase chain reaction assay is a reliable method to detect FUS-CREB3L2, which can thus help in accurately diagnosing LGFMS.

The development of an active drug delivery system is an attractive approach to increase the targetability of anticancer agents. In the present study, we examined the efficiency of systemic chemotherapy with small magnetic liposomes containing doxorubicin (magnetic DOX liposomes) and an externally applied electromagnetic force in osteosarcoma-bearing hamsters. Syrian male hamsters inoculated with osteosarcoma, OS515, in the limb were studied 7 days after inoculation. The efficiency of this system was evaluated by measuring the tissue distribution and tumor-suppressing effects of DOX on primary tumor growth and lung metastases. A DC dipole electromagnet was used, and the hamster's tumor-bearing limb was placed between 2 poles after the i.v. administration of liposomes. The dose of DOX and the magnetic field strength were fixed at 5 mg/kg and 0.4 T, respectively. Administration of magnetic DOX liposomes followed by 60 min application of magnetic field produced a 3- to 4-fold higher maximum DOX concentration in the tumor. This newly designed systemic chemotherapy significantly suppressed primary tumor growth for at least 2 weeks, though other DOX treatments also suppressed compared to control. Histologic examination confirmed a greater antitumor effect of this systemic chemotherapy compared to standard methods. In addition, this approach significantly suppressed lung metastases measured at 3 weeks posttreatment. These results suggest that this systemic chemotherapy can effectively reduce primary tumor growth and suppress lung metastasis due to increased targeting of DOX. Such targeted drug delivery for anticancer agents would provide clinical advantages compared to current methods.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) often accompanies lung cancer, and life-threatening acute exacerbation (AE) of IPF (AE-IPF) is reported to occur in 20 % of IPF patients who undergo lung cancer surgery. Pirfenidone is an anti-fibrotic agent known to reduce disease progression in IPF patients. A phase II study was conducted to evaluate whether perioperative pirfenidone treatment could reduce the incidence of postoperative AE-IPF patients with lung cancer. METHODS: Pirfenidone was orally administered to IPF patients who were candidates for lung cancer surgery; pirfenidone was dosed at 600 mg/day for the first 2 weeks, followed by 1200 mg/day. Surgery was performed after at least 2 weeks of 1200-mg/day administration. The primary endpoint was non-AE-IPF rate during postoperative days 0-30, compared to the null value of 80 %, and the secondary endpoint was safety. Radiologic and pathologic diagnoses of IPF and AE-IPF were confirmed by an independent review committee. RESULTS: From June 2012 to January 2014, 43 cases were enrolled, and 39 were eligible (full analysis set [FAS]). Both pirfenidone treatment and surgery were performed in 36 patients (per protocol set [PPS]). AE-IPF did not occur in 37/39 patients (94.9 % [95 % confidential interval: 82.7-99.4 %, p = 0.01]) in the FAS, and in 38/39 patients (97.2 % [95 % confidential interval: 85.5-99.9 %, p = 0.004] in the PPS. A grade 5 adverse event (death) occurred in 1 patient, after AE-IPF; no other grade 3-5 adverse events were observed. CONCLUSIONS: Perioperative pirfenidone treatment is safe, and is promising for reducing AE-IPF after lung cancer surgery in IPF patients. TRIAL REGISTRATION: This clinical trial was registered with the University Hospital Medical Information Network (UMIN) on April 16th, 2012 (REGISTRATION NUMBER: UMIN000007774 ).

Prevention therapy is recommended for lesions >1/2 of the esophageal circumference. Locoregional steroid injection is recommended for lesions >1/2-3/4 of the esophageal circumference and oral steroids are recommended for lesions >1/2 of the subtotal circumference. For lesions of the entire circumference, oral steroid combined with injection steroid is considered. Endoscopic balloon dilatation (EBD) is the first choice of treatment for stricture after esophageal endoscopic submucosal dissection (ESD). Radical incision and cutting or self-expandable metallic stent can be considered for refractory stricture after EBD. In case of intraoperative perforation during esophageal ESD, endoscopic clip closure should be initially attempted. Surgery is considered for treatment of delayed perforation. Current standard practice for prevention of delayed bleeding after gastric ESD includes prophylactic coagulation of vessels on post-ESD ulcers and giving proton pump inhibitors. Chronic kidney disease stage 4 or 5, multiple antithrombotic drug use, anticoagulant use, and heparin bridging therapy are high-risk factors for delayed bleeding after gastric ESD. Intraoperative perforation during gastric ESD is initially managed by endoscopic clip closure. If endoscopic clip closure is difficult, other methods such as over-the-scope clip (OTSC), polyglycolic acid (PGA) sheet shielding etc. are attempted. Delayed perforation usually requires surgical intervention, but endoscopic closure by OTSC or PGA sheet may be considered. Resection of three-quarters of the circumference is a risk factor for stenosis after gastric ESD. Giving prophylactic local steroid injection and/or oral steroid is reported, but effectiveness has not been fully verified as has been done for esophageal stricture. The main management method for gastric stenosis is EBD but it may cause perforation.

BACKGROUND: Catheter ablation of atrial fibrillation (AF) became an effective therapy for patients with drug-refractory AF, and the indications have broadened to include nonparoxysmal AF patients. However, data about the long-term effectiveness of ablation in patients with nonparoxysmal AF are lacking. The aim of the present study was to investigate the long-term outcomes of catheter ablation in patients with nonparoxysmal AF. METHODS AND RESULTS: A total of 88 nonparoxysmal AF patients who received a stepwise catheter ablation (isolation of the pulmonary veins plus substrate modification) from 2006 to 2008 were enrolled. Freedom of recurrence was defined as the absence of atrial arrhythmias without using any antiarrhythmic agents after the catheter ablation. There were 63 patients (71.6%) with recurrences (47 patients with AF and 16 patients with atrial flutter/atrial tachycardia) after the initial procedure during a median follow-up period of 36.8 months. A CHADS2 score of ≥3 and the left atrial (LA) diameter were significant predictors of recurrences in the multivariable analysis. Of the patients with CHADS2 scores of ≥3 and an LA dimension≥44 mm, all had recurrences within 1 year after the initial procedure. The overall recurrence-free rate could increase to 47.7% after the second procedure and 51.1% after the third procedure. CONCLUSIONS: The long-term recurrence-free rate of ablation in nonparoxysmal AF was only 28.4% after a single procedure, and multiple procedures were necessary to raise the recurrence-free rate. The CHADS2 score and LA dimension may help us to identify patients who will have recurrences after catheter ablations of nonparoxysmal AF.

AIM: We surveyed multiple centers to identify types and frequency of complications and mortality rate associated with radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). METHODS: We distributed a questionnaire developed by members of the Chugoku-Shikoku Society for the Local Ablation Therapy of Hepatocellular Carcinoma to 20 centers and analyzed types and frequency of complications and mortality rate. RESULTS: In total, 16 346 nodules were treated in 13 283 patients between January 1999 and November 2010. Five patients (0.038%) died: two from intraperitoneal hemorrhage, and one each from hemothorax, severe acute pancreatitis and perforation of the colon. In 16 346 treated nodules, 579 complications (3.54%) were observed, including 78 hemorrhages (0.477%), 276 hepatic injuries (1.69%), 113 extrahepatic organ injuries (0.691%) and 27 tumor progressions (0.17%). The centers that treated a large number of nodules and performed RFA modifications, such as use of artificial ascites, artificial pleural effusion and bile duct cooling, had low complication rates. CONCLUSION: This study confirmed that RFA is a low-risk treatment for HCC and that sufficient experience and technical skill can reduce complications.

Airway stenting at the wave-speed flow-limiting segment (the choke point) is assessed. We determined prospectively the precise location of the choke point using the flow-volume curve, endobronchial ultrasonography, ultrathin bronchoscopy, and three-dimensional computed tomography scan before and after stenting in 64 patients with extrincic compression due to lung cancer. We noted distinct flow-volume curve patterns specific to the type of stenosis. The tracheal stenosis group indicated fixed narrowing patterns with an expiratory plateau, bronchial stenosis group dynamic collapse patterns with an expiratory flow deterioration (choking), carinal stenosis group combined fixed and dynamic patterns, and extensive stenosis group complex patterns containing elements of all the former. After stenting, almost full-function patterns with significant improvement in PEF were observed in all groups (p < 0.01, p < 0.05, p < 0.001, p < 0.01, respectively). In patients with extensive stenosis, implantation of additional stents was required when the choke points were observed to have migrated to the areas of malacia with cartilage destruction by the tumor. Secondary stenting at migrated choke points resulted in a significant improvement in PEF over the initial stenting (p < 0.01). Stenting at the choke point improved expiratory flow limitation by increasing the cross-sectional area, supporting the weakened airway wall and relieving dyspnea.

This prospective study was designed to elucidate the duration of systemic inflammatory response syndrome (SIRS) and the mechanisms that lead to the protraction of SIRS in patients who are operated on under cardiopulmonary bypass (CPB).The duration of SIRS in 13 patients with SIRS was studied. Two groups were divided according to the duration to investigate the meaning of the duration of SIRS. The perioperative parameters which significantly correlated with the duration of SIRS, including the kinetics of cytokines and white blood cells (WBC) counts were investigated.In patients with SIRS extending for a period greater than 12 hours (group A), the duration of CPB, interleukin-6 (IL-6), interleukin-8 (IL-8) and WBC count after aortic declamping were significantly longer and higher than those in patients with SIRS lasting less than 12 hours (group B). The duration of SIRS significantly correlated with the highest level of IL-6 (r=0.724, p=0.0038) and the duration of CPB (r=0.626, p=0.0201).These results suggest that the duration of CPB and cytokinemia, with high IL-6 levels, during this short time frame until just after cardiac surgery might play an important role in the development of the SIRS.

BACKGROUND: Neutrophil elastase plays an important role in the development and progression of acute respiratory distress syndrome (ARDS). Although the selective elastase inhibitor, sivelestat, is widely used in Japan for treating ARDS patients, its effectiveness remains controversial. The aim of the current study was to investigate the effects of sivelestat in ARDS patients with evidence of increased extravascular lung water by re-analyzing a large multicenter study database. METHODS: A post hoc analysis of the PiCCO Pulmonary Edema Study was conducted. This multicenter prospective cohort study included 23 institutions in Japan. Adult mechanically ventilated ARDS patients with an extravascular lung water index of >10 mL/kg were included and propensity score analyses were performed. The endpoints were 28-day mortality and ventilator-free days (VFDs). RESULTS: Patients were categorized into sivelestat (n = 87) and control (n = 77) groups, from which 329 inverse probability-weighted group patients (162 vs. 167) were generated. The overall 28-day mortality was 31.1% (51/164). There was no significant difference in 28-day mortality between the study groups (sivelestat vs. control; unmatched: 29.9% vs. 32.5%; difference, -2.6%, 95% confidence interval (CI), -16.8 to 14.2; inverse probability-weighted: 24.7% vs. 29.5%, difference, -4.8%, 95% CI, -14.4 to 9.6). Although administration of sivelestat did not alter the number of ventilator-free days (VFDs) in the unmatched (9.6 vs. 9.7 days; difference, 0.1, 95% CI, -3.0 to 3.1), the inverse probability-weighted analysis identified significantly more VFDs in the sivelestat group than in the control group (10.7 vs. 8.4 days, difference, -2.3, 95% CI, -4.4 to -0.2). CONCLUSIONS: Although sivelestat did not significantly affect 28-day mortality, this treatment may have the potential to increase VFDs in ARDS patients with increased extravascular lung water. Prospective randomized controlled studies are required to confirm the results of the current study.