Radiologic-histopathologic correlation of fatty island sign with fat necrosis in atypical lipomatous tumor and lipoma.

AIM: This study aimed to assess the imaging features of atypical lipomatous tumors (ALTs) and lipoma with fat necrosis. METHODS: This study included patients with histopathologically proven fat necrosis within adipocytic tumors who underwent preoperative imaging. Magnetic resonance imaging (MRI) and/or computer tomography (CT) findings of fat necrosis associated with lipomatous tumors were retrospectively reviewed, emphasizing the "fatty island sign (FIS)." FISs were defined as well-demarcated, focal fat-containing areas surrounded by more thickened septa compared with other intratumoral septa. Imaging findings of FIS were compared between ALT and lipoma. RESULTS: Fat necrosis was histopathologically confirmed in 17 patients (6 ALTs and 11 lipomas). Among them, 18 FISs were observed in 10 lesions (59%). Multiple FISs within a lesion were observed in 4 (40%) patients. The median maximum diameter of the FISs was 37 mm. Hypointense areas within FISs relative to the subcutaneous fat on T1- and T2-weighted images were observed in 8 (80%) and 9 (90%), respectively, whereas hyperintense areas within FISs on fat-suppressed T2-weighted images were observed in 2 (20%). Nonfatty solid components within FISs were observed in 2 (20%). On CT, increased fat attenuation and pure fat attenuation within FISs were observed in 6 (86%) and 1 (14%), respectively. The imaging findings of FIS were not significantly different between ALT and lipoma. CONCLUSION: FISs were observed in 59% of the histologically proven ALT and lipoma patients with fat necrosis. The hypointense areas relative to the subcutaneous fat on T1- and T2-weighted images and increased fat attenuation on CT were usually observed within FISs.

Effect of X-ray tube on image quality and pancreatic ductal adenocarcinoma conspicuity in pancreatic protocol dual-energy CT.

AIM: To compare the radiation dose, image quality, and conspicuity of pancreatic ductal adenocarcinoma (PDAC) in pancreatic protocol dual-energy computed tomography (CT) between two X-ray tubes mounted in the same CT machine. MATERIAL AND METHODS: This retrospective study comprised 80 patients (median age, 73 years; 45 men) who underwent pancreatic protocol dual-energy CT from January 2019 to March 2022 using either old (Group A, n=41) or new (Group B, n=39) X-ray tubes mounted in the same CT machine. The imaging parameters were completely matched between the two groups, and CT data were reconstructed at 70 and 40 keV. The CT dose-index volume (CTDIvol); CT attenuation of the abdominal aorta, pancreas, and PDAC; background noise; and qualitative scores for the image noise, overall image quality, and PDAC conspicuity were compared between the two groups. RESULTS: The CTDIvol was lower in Group B than Group A (7.9 versus 9.2 mGy; p<0.001). The CT attenuation of all anatomical structures at 70 and 40 keV was comparable between the two groups (p=0.06-0.78). The background noise was lower in Group B than Group A (12 versus 14 HU at 70 keV, p=0.046; and 26 versus 30 HU at 40 keV, p<0.001). Qualitative scores for image noise and overall image quality at 70 and 40 keV and PDAC conspicuity at 40 keV were higher in Group B than Group A (p<0.001-0.045). CONCLUSION: The latest X-ray tube could reduce the radiation dose and improve image quality in pancreatic protocol dual-energy CT.

Computed Tomography and 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography Imaging Biomarkers of Lung Invasive Non-mucinous Adenocarcinoma: Prediction of Grade 3 Tumour Based on World Health Organization Grading System.

AIMS: To evaluate computed tomography (CT) and 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) findings of invasive non-mucinous adenocarcinoma (INMA) of the lung as a predictor of histological tumour grade according to 2021 World Health Organization (WHO) classification. MATERIALS AND METHODS: This retrospective study included consecutive patients with surgically resected INMA who underwent both preoperative CT and 18F-FDG-PET/CT. A three-tiered tumour grade was performed based on the fifth edition of the WHO classification of lung tumours. CT imaging features and the maximum standardised uptake value (SUVmax) were compared among the three tumour grades. RESULTS: In total, 214 patients with INMA (median age 70 years; interquartile range 65-76 years; 123 men) were histologically categorised: 36 (17%) as grade 1, 102 (48%) as grade 2 and 76 (35%) as grade 3. Pure solid appearance was more frequent in grade 3 (83%) than in grades 1 (0%) and 2 (26%) (P < 0.001). The SUVmax of the entire tumour was higher in grade 3 than in grades 1 and 2 (P < 0.001). Multivariable analysis revealed that pure solid appearance (odds ratio = 94.0; P < 0.001), round/oval shape (odds ratio = 4.01; P = 0.001), spiculation (odds ratio = 2.13; P = 0.04), air bronchogram (odds ratio = 0.40; P = 0.03) and SUVmax (odds ratio = 1.45; P < 0.001) were significant predictors for grade 3 INMAs. CONCLUSION: Pure solid appearance, round/oval shape, spiculation, absence of air bronchogram and high SUVmax were associated with grade 3 INMAs. CT and 18F-FDG-PET/CT were potentially useful non-invasive imaging methods to predict the histological grade of INMAs.

Deep-learning-based image reconstruction in dynamic contrast-enhanced abdominal CT: image quality and lesion detection among reconstruction strength levels.

AIM: To evaluate the use of deep-learning-based image reconstruction (DLIR) algorithms in dynamic contrast-enhanced computed tomography (CT) of the abdomen, and to compare the image quality and lesion conspicuity among the reconstruction strength levels. MATERIALS AND METHODS: This prospective study included 59 patients with 373 hepatic lesions who underwent dynamic contrast-enhanced CT of the abdomen. All images were reconstructed using four reconstruction algorithms, including 40% adaptive statistical iterative reconstruction-Veo (ASiR-V) and DLIR at low, medium, and high-strength levels (DLIR-L, DLIR-M, and DLIR-H, respectively). The signal-to-noise ratio (SNR) of the abdominal aorta, portal vein, liver, pancreas, and spleen and the lesion-to-liver contrast-to-noise ratio (CNR) were calculated and compared among the four reconstruction algorithms. The diagnostic acceptability was qualitatively assessed and compared among the four reconstruction algorithms and the conspicuity of hepatic lesions was compared between <5 and ≥5 mm lesions. RESULTS: The SNR of each anatomical structure (p<0.0001) and CNR (p<0.0001) were significantly higher in DLIR-H than the other reconstruction algorithms. Diagnostic acceptability was significantly better in DLIR-M than the other reconstruction algorithms (p<0.0001). The conspicuity of hepatic lesions was highest when using 40% ASiR-V and tended to lessen as the reconstruction strength level was getting higher in DLIR, especially in <5 mm lesions; however, all hepatic lesions could be detected. CONCLUSIONS: DLIR improved the SNR, CNR, and image quality compared with 40% ASiR-V, while making it possible to decrease lesion conspicuity using higher reconstruction strength.

Immunological inflammatory biomarkers as prognostic predictors for advanced hepatocellular carcinoma.

BACKGROUND: The immunological inflammatory biomarkers for advanced hepatocellular carcinoma are unclear. We aimed to investigate the association of immunity and inflammatory status with treatment outcomes in patients with advanced hepatocellular carcinoma who received molecular-targeted agents as primary treatment. PATIENTS AND METHODS: We enrolled 728 consecutive patients with advanced hepatocellular carcinoma who received sorafenib (n = 554) or lenvatinib (n = 174) as primary treatment in Japan between May 2009 and June 2020. Changes in the neutrophil-to-lymphocyte ratio before and 1 month after treatment and their impact on survival were evaluated. The cut-off values of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for predicting overall and progression-free survival were calculated using receiver operating characteristic curves. RESULTS: The neutrophil-to-lymphocyte ratio, but not the platelet-to-lymphocyte ratio, was an independent prognostic factor. Patients with decreased neutrophil-to-lymphocyte ratio survived significantly longer than patients with increased neutrophil-to-lymphocyte ratio (median overall survival: 14.7 versus 10.4 months, P = 0.0110). Among patients with a low pre-treatment neutrophil-to-lymphocyte ratio, the overall survival did not differ significantly between those with decreased and those with increased neutrophil-to-lymphocyte ratio after 1 month (median: 19.0 versus 14.8 months, P = 0.1498). However, among patients with high pre-treatment neutrophil-to-lymphocyte ratio, those whose neutrophil-to-lymphocyte ratio decreased after 1 month showed significantly longer survival than those whose neutrophil-to-lymphocyte ratio increased (median: 12.7 versus 5.5 months, P < 0.0001). The therapeutic effect was not correlated with pre-treatment neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio. CONCLUSIONS: The neutrophil-to-lymphocyte ratio is a prognostic factor, along with liver function and tumor markers, in patients with advanced hepatocellular carcinoma who received molecular-targeted agents as primary treatment. Thus, the neutrophil-to-lymphocyte ratio could be a prognostic biomarker for advanced hepatocellular carcinoma primarily treated with immunotherapy.

Virtual monochromatic image at lower energy level for assessing pancreatic ductal adenocarcinoma in fast kV-switching dual-energy CT.

AIM: To evaluate the value of virtual monochromatic images (VMIs) at lower energy levels in fast-voltage-switching dual-energy computed tomography (DECT) for assessing pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: The institutional review board approved this prospective study. Written informed consent was obtained from all patients. Seventy-four consecutive patients with PDAC underwent dynamic contrast-enhanced DECT. Two radiologists reviewed eight energy levels (40, 45, 50, 55, 60, 65, 70, and 75 keV) of the pancreatic parenchymal phase VMIs. CT attenuation of the PDAC and pancreatic parenchyma, background noise, signal-to-noise ratio (SNR) of the pancreas, tumour-to-pancreas contrast-to-noise ratio (CNR), major and minor axes of PDAC, and qualitative tumour conspicuity were compared among the VMIs at eight energy levels. RESULTS: CT attenuation of PDAC and pancreatic parenchyma, background noise, SNR, and CNR peaked on VMIs at 40 keV with statistically significant difference (p<0.0001) and gradually decreased with increasing energy levels. The reproducibility in measuring tumour size was better on VMIs at 40 keV (28.8 and 29.2 mm of major axis in readers 1 and 2, respectively) and tended to be overestimated at higher energy levels (29.8 and 30.9 mm of major axis at 75 keV in readers 1 and 2, respectively). Qualitative tumour conspicuity was also significantly superior on VMIs at 40 keV than at all other energy levels (p<0.0001). CONCLUSION: VMIs at 40 keV demonstrated significantly increased SNR of the pancreas, CNR, and tumour conspicuity and high reproducibility in measuring tumour size for assessing PDAC.

Pancreatic MRI associated with pancreatic fibrosis and postoperative fistula: comparison between pancreatic cancer and non-pancreatic cancer tissue.

AIM: To evaluate the potential value of magnetic resonance imaging (MRI) for predicting postoperative pancreatic fistula (POPF) in patients with pancreatic cancer (PC) and non-pancreatic cancer (non-PC). MATERIAL AND METHODS: This retrospective study was approved by the institutional review board and written informed consent was waived. Forty patients underwent pancreatoduodenectomy due to PC (n=31) and non-PC (n=9). The pancreas-to-muscle signal intensity ratio (SIR) on three-dimensional (3D)- fast field echo (FFE) T1-, in- and opposed-phase T1-, and T2-weighted images, as well as the apparent diffusion coefficient (ADC) value of the pancreas were measured. The frequency of POPF and MRI measurements were compared between patients with PC and non-PC. The MRI measurements were also compared with the grade of pancreatic fibrosis on pathological findings, fat deposition, and interstitial oedema. RESULTS: The frequency of POPF was significantly higher in patients with non-PC than in those with PC (p=0.0067), with an odds ratio of 10.4. The SIR on 3D-FFE T1-weighted images was significantly higher in patients with non-PC (p=0.0001) and those with POPF (p=0.017) than in those with PC and those without POPF, respectively. Multiple regression analysis demonstrated that the SIR on 3D-FFE T1-weighted image was independently associated with the grade of pancreatic fibrosis (p<0.0001). CONCLUSION: The frequency of POPF was significantly higher in patients with non-PC than in those with PC was inversely related to the grade of pancreatic fibrosis. The SIR on 3D-FFE T1-weighted image might be a potential imaging biomarker for predicting POPF.

Neuropeptide VGF-Derived Peptide LQEQ-19 has Neuroprotective Effects in an In Vitro Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease caused by the loss of upper and lower motor neurons resulting in muscle weakness and paralysis. Recently, VGF, a neuropeptide that is a precursor of bioactive polypeptides, was found to be decreased in ALS patients, and its inducer exerted protective effects in models of ALS. These findings suggested that VGF was involved in the pathology of ALS. Here, we investigated the neuroprotective effects of various VGF-derived peptides in an in vitro ALS model. We applied seven VGF-derived peptides (TLQP-21, AQEE-30, AQEE-11, LQEQ-19, QEEL-16, LENY-13, and HVLL-7) to the motor neuron-derived cell line, NSC-34, expressing SOD1G93A, which is one of the mutated proteins responsible for familial ALS. Nuclear staining revealed that AQEE-30 and LQEQ-19, which are derived from the C-terminal polypeptide of the VGF precursor protein, attenuated neuronal cell death. Furthermore, immunoblot analysis demonstrated that LQEQ-19 promoted the phosphorylation of Akt and extracellular signal-regulated kinase (ERK) 1/2, and inhibiting these mitogen-activated MAP kinases (MAPKs) with phosphoinositide 3-kinase or MEK/ERK inhibitors, eliminated the neuroprotective effects of LQEQ-19. In conclusion, these results suggest that VGF C-terminal peptides exert their neuroprotective effects via activation of MAPKs such as Akt and ERK1/2. Furthermore, these findings indicate that VGF-derived peptides have potential application in ALS therapy.

Polypoidal choroidal vasculopathy and history of central serous chorioretinopathy.

PURPOSE: To evaluate the possible causative role of central serous chorioretinopathy (CSC) in the development of exudative age-related macular degeneration (AMD). METHODS: In a cross-sectional study at an institutional setting, 150 control subjects who had senile cataract or nasolacrimal duct stenosis and who were older than 50 years were enrolled. The background data for 89 patients with typical AMD (tAMD) and 138 patients with polypoidal choroidal vasculopathy (PCV) were used for comparison. Their medical records were taken for history of CSC, hypertension, systemic steroid use, and smoking. The fundus was also evaluated for signs of atrophic retinal pigment epithelial (RPE) tract and for focal photocoagulation scars in the macula. RESULTS: After adjusting for age, gender, and history of hypertension, systemic steroid use, and smoking, history of CSC was significantly more frequent (P<0.0001) in patients with PCV (15 patients, 10.9%) compared with patients with tAMD (2 patients, 2.2%) or control subjects (0 patients). On fundoscopy, an atrophic RPE tract (seven patients) or a focal photocoagulation scar (one patient) was observed only in patients with PCV (eight patients, 5.8%), and the frequency was statistically significant compared with that with tAMD (P=0.0143) or control subjects (P=0.0143). The laterality of CSC and AMD involved the same eye in 9 of 10 patients among those who had unilateral AMD and a reported unilateral CSC history. CONCLUSION: A history of CSC may be a predisposing factor for the development of PCV in the Japanese population.

Vascular image in autoimmune pancreatitis by contrast-enhanced color-Doppler endoscopic ultrasonography: Comparison with pancreatic cancer.

INTRODUCTION: In autoimmune pancreatitis (AIP), veins of various sizes are highly affected by obliterative phlebitis without damage to arteries, in contrast, the involvement of both arteries and veins is observed in the mass of pancreatic cancer. A vascular image without blooming artifact in the pancreas is clearly observed in the directional eFLOW (Prosound α10, Aloca Co., Tokyo, Japan) color mode using contrast-enhanced color-Doppler endoscopic ultrasonography (CC-EUS) despite perfusion of the contrast media. AIMS AND METHODS: The aim of this study was to compare the vascular structure of AIP with that of pancreatic cancer using CC-EUS. We evaluated the perfusion image and the vascular image of the mass in AIP patients (11) with an increase in serum IgG4 levels (477.3 ± 314.2 IU/mL) and in pancreatic cancer patients (11) with elevated serum CA19-9 levels (49839.0 ± 80061.6 mg/dl), on CC-EUS. Perfusion images were obtained at 20-30 s after injection of a contrast agent, Sonazoid (GE Healthcare AG, Oslo, Norway), by extended pure harmonic detection mode and were assessed as to homogeneity or heterogeneity (containing partial low echoic areas or multiple spotty low echoic areas) enhancement. The vascular image was assessed in the directional eFLOW color mode despite perfusion of the contrast media (40-50 s after injection of Sonazoid) as to the presence of a dendritic vessel network or only a few feeder vessels. The parameters for imaging were as follows: Mechanical index, 0.22-0.24; transmission frequency, 5.0 MHz; and receiving frequency, 5.0 MHz. The Chi-square test or Fisher's exact test was used for comparison of categorical data of the two groups when appropriate. This study was approved by the institutional review board of Sendai City Medical Center. All subjects gave informed consent. RESULTS: A homogenous pattern in perfusion imaging was seen in 73% of patients with AIP (8/11) and 55% of those with pancreatic cancer (6/11). The rates were not significantly different between the two groups (P = 0.33). In the other patients with a heterogenous pattern, multiple spotty low echoic areas were seen in 33% (1/3) and 80% (4/5) in each group, respectively. A dendritic vascular pattern in the eFLOW color mode was seen in 82% (9/11) of patients with AIP, but was not seen in any of patients with pancreatic cancer. The other patients with AIP (18%) and all patients with pancreatic cancer showed only a few feeder vessels in the mass on CC-EUS. CONCLUSION: The eFLOW color mode using Sonazoid may be useful for evaluating the vascular structure of AIP for differential diagnosis from pancreatic cancer.

A prospective, randomized, double-blind, controlled trial on the efficacy of carbon dioxide insufflation in gastric endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Carbon dioxide (CO2) insufflation is expected to be safe and effective in endoscopic submucosal dissection (ESD) as well as in other endoscopic procedures. The present study aimed to clarify the usefulness and safety of CO2 insufflation in gastric ESD. PATIENTS AND METHODS: A total of 102 consecutive patients were randomly assigned to CO2 insufflation (CO2 group, n = 54) or air insufflation (Air group, n = 48). Abdominal pain and distension were chronologically recorded on a 100-mm visual analog scale (VAS). The volume of residual gas in the digestive tract was measured by computed tomography performed immediately after ESD. RESULTS: Abdominal pain on a 100-mm VAS in the CO2 vs. Air group was 4 vs. 3 immediately after ESD, 4 vs. 4 one hour after the procedure, 3 vs. 3 three hours after the procedure, and 1 vs. 4 the next morning, showing no difference between the groups. In addition, there was no difference in abdominal distension on the 100-mm VAS over the time course of the study. The volume of residual gas in the digestive tract in the CO2 group was significantly smaller than that in the Air group (643 mL vs. 1037 mL, P < 0.001). The dose of sedative drugs did not differ between the groups. Neither the incidences of complications nor clinical courses differed between the groups. CONCLUSIONS: Compared with air insufflation, CO2 insufflation during gastric ESD significantly reduced the volume of residual gas in the digestive tract but not the VAS score of abdominal pain and distension.

COX/PGE(2) axis critically regulates effects of LPS on eosinophilia-associated cytokine production in nasal polyps.

BACKGROUND: Lipopolysaccharide (LPS) has shown heterogeneous effects on eosinophilic inflammation in airways. However, little is known about how LPS regulates pathogenesis of chronic rhinosinusitis with nasal polyps, a major form of eosinophilic inflammation in the upper airway. OBJECTIVE: We sought to investigate the effect of LPS on cytokine production by dispersed nasal polyp cells (DNPCs). METHODS: Either diclofenac-treated or untreated DNPCs were cultured with or without staphylococcal enterotoxin B (SEB) in the presence or absence of LPS, after which the levels of IL-5, IL-13, IL-17A and IFN-γ within the supernatant were measured. The effects of PGE(2) on LPS-induced responses by diclofenac-treated DNPCs were also examined. LPS-induced PGE(2) production and mRNA expression of COX-1, COX-2 and microsomal PGE(2) synthase-1 (m-PGES-1) were measured. RESULTS: Staphylococcal enterotoxin B induced IL-5, IL-13, IL-17A and IFN-γ production by DNPCs. Pre-treatment with LPS prior to SEB stimulation inhibited production of these cytokines. After stimulation with LPS, PGE(2) production and expression of COX-2 and m-PGES-1 mRNA by DNPCs increased significantly. In the presence of diclofenac, the suppressive effects of LPS were eliminated. LPS pre-treatment enhanced SEB-induced IL-5, IL-13 and IL-17A production in diclofenac-treated DNPCs, while addition of PGE(2) inhibited IL-5, IL-13 and IFN-γ production. LPS alone induced IL-5, IL-13 and IFN- γ production by diclofenac-treated DNPCs, while the addition of EP2 and EP4 receptor-selective agonists, as well as PGE(2) itself, inhibited IL-5 and IL-13 production. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that the regulatory effects of LPS on eosinophilic airway inflammation are controlled via the COX-2/PGE(2) axis. For clinical implications, indiscreet use of non-steroidal anti-inflammatory drugs should be avoided in patients with chronic rhinosinusitis with nasal polyps.

Mesenteric phlebosclerosis associated with long-term oral intake of geniposide, an ingredient of herbal medicine.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare disease, characterised by thickening of the wall of the right hemicolon with calcification of mesenteric veins. However, the aetiology remains unknown. AIM: To investigate the possible association of herbal medicines with IMP. METHOD: The clinical data of four of our own patients were collected. Furthermore, we searched for previous reports about similar patients with detailed descriptions of herbal prescriptions that they had taken. We compared herbal ingredients to identify the toxic agent as a possible aetiological factor. RESULTS: Clinical data on a total of 25 patients were summarised. Mean age was 61.8 years and there was female predominance (6 men and 19 women). The used Kampo prescription, the number of cases, and the mean duration of use were as follows: kamisyoyosan in 12 cases for 12.8 years, inshin-iseihaito in 5 cases for 13.4 years, orengedokuto in 4 cases for 14.3 years, inchinkoto in 1 case for 20 years, kamikihitou in 1 case for 19 years, seijobofuto in 1 case for 10 years and gorinsan in 1 case for an unknown duration. Only one ingredient, sansisi, was common to the herbal medicines of all 25 patients. This crude drug called geniposide in English is a major constituent of the Gardenia fruits. CONCLUSION: The long-term use of geniposide in herbal medicines appears to be associated with mesenteric phlebosclerosis.

A pilot study to assess mediastinal emphysema after esophageal endoscopic submucosal dissection with carbon dioxide insufflation.

BACKGROUND AND AIMS: Mediastinal emphysema sometimes develops following esophageal endoscopic submucosal dissection (ESD) without perforation because the esophagus has no serosa. Carbon dioxide (CO2) insufflation during esophageal ESD may reduce the incidence of mediastinal emphysema. The aim of the present study was to compare the incidence and severity of post-ESD mediastinal emphysema in patients receiving CO2 insufflation vs. standard air insufflation during esophageal ESD. PATIENTS AND METHODS: A total of 27 patients who had undergone esophageal ESD with insufflation of CO2 between July 2009 and March 2010 were enrolled in this study (CO2 group). Another 105 patients who had undergone esophageal ESD with air insufflation between March 2004 and May 2009 were included as historical controls (air group). Multi-detector row computed tomography (MDCT) was carried out immediately after ESD. A conventional chest radiograph was taken the next day. Mediastinal emphysema findings on MDCT and radiography were compared between the groups. RESULTS: Mediastinal emphysema detected by chest radiography was 0 % in the CO2 group vs. 6.6 % in the air group (n.s.). Mediastinal emphysema on MDCT was significantly less frequent in the CO2 group compared with the air group (30 % vs. 63 %; P = 0.002). The severity of mediastinal emphysema also tended to be lower in the CO2 group. CONCLUSIONS: Whereas mediastinal emphysema detected by radiography is not so common, MDCT immediately after ESD revealed a certain prevalence of post-ESD mediastinal emphysema. Insufflation of CO2 rather than air during esophageal ESD significantly reduced postprocedural mediastinal emphysema. CO2 can be considered as insufflating gas for esophageal ESD.

Renal impairment after laparoscopic radical nephrectomy affects hypoglycaemic therapy.

WHAT IS KNOWN AND OBJECTIVE: Renal impairment is unavoidable after laparoscopic radical nephrectomy (LRN) and is an important consideration for drug therapy. It is possible that the renal impairment after LRN causes adverse reactions following reduced elimination of some renally excreted drugs, such as hypoglycaemic drugs. However, there are few studies of renal function in patients with diabetes mellitus (DM) in the first week after LRN. The purpose of this study was to examine whether renal impairment after LRN affected glycaemic control. We assessed pre- and postoperative renal function of DM patients and examined whether re-administration of hypoglycaemic drugs in the first week after LRN causes episodes of hypoglycaemia. METHODS: Renal carcinoma patients undergoing LRN in Nagoya University Hospital from January 2007 to December 2009 were identified in a retrospective cohort study design. Patients were divided into non-DM (n = 60) and DM (n = 14) groups. RESULTS AND DISCUSSION: There were significant differences in postoperative estimated glomerular filtration rate values between the non-DM and DM groups. Four of nine patients (44%) experienced hypoglycaemia induced by re-administration of hypoglycaemic drugs, namely, sulfonylureas. WHAT IS NEW AND CONCLUSION: In the present study, we found the first evidence that renal impairment in the first week after LRN was a risk factor of hypoglycaemia. To prevent hypoglycaemia after LRN, assessment of renal function and the use of insulin therapy are important.

Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma.

WHAT IS KNOWN AND OBJECTIVE: Montelukast, a cysteinyl leukotriene receptor 1 antagonist, is safe and efficacious in patients with asthma. The mechanisms underlying the significant interpatient variability in response to montelukast are not clear but are believed to be, in part, because of genetic variability. METHODS: To examine the associations between polymorphisms in candidate genes in the leukotriene pathway and outcomes in patients with asthma on montelukast for 4-8 weeks, we evaluated the changes in peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV(1·0) ) and patients' subjective symptom before and after montelukast treatment. DNA was collected from 252 Japanese participants. RESULTS AND DISCUSSION: Two single-nucleotide polymorphisms (SNPs) in the ALOX5 (rs2115819) and LTA4H (rs2660845) genes were successfully typed. There was no difference between members of the general population (n = 200) and patients (n = 52) in each genotype frequency. Significant associations were found between SNP genotypes in the LTA4H gene and changes in PEF and FEV(1·0) . The PEF and FEV(1·0) responses to montelukast in the A/A genotypes (n = 4) for the LTA4H SNP were significantly higher than those in the G allele carriers (A/G+G/G) (n = 17). WHAT IS NEW AND CONCLUSION: Despite the small sample size, our results suggest that genetic variation in leukotriene pathway candidate genes contributes to variability in clinical responses to montelukast in Japanese patients with asthma.

Mutant mouse p53 transgene elevates the chemical induction of tumors that respond to gene silencing with siRNA.

To study the role of mutant p53 in the induction and cure of tumors, we generated transgenic mice carrying mutant p53 (mp53) containing a 9 bp deletion in exon 6 in addition to wild-type p53, expressing both p53 and mp53. The mp53 cDNA was cloned from a radiation-induced mouse tumor and ligated to the chicken beta-actin promoter/CMV-IE enhancer in the expression vector. The presence of mp53 suppressed p21 expression in primary fibroblasts after ionizing irradiation, indicating the dominant-negative activity of mp53 in the mice. These mice developed fibrosarcomas after the subcutaneous injection of 3-methylcholanthrene with an incidence 1.7-fold higher than that of wild-type mice (42% excess). The tumors were then treated via a potent atelocollagen delivery system with small interfering RNA (siRNA), that targeted the promoter/enhancer of the expression vector, resulting in the suppression of tumor growth in 30% of 44 autochthonous tumors, including four cures, and their transplants, the total fraction corresponding to the tumor excess. This suppressive effect involved the induction of apoptosis. These results indicate that mp53 activity causes tumors that can be suppressed by subsequent silencing of mp53 in the presence of wild-type p53 alleles.

A new technique using free ileocaecal patch transplantation for secondary voice restoration after total laryngectomy.

SUMMARY: We introduce our newly designed voice restoration technique, which uses free ileocaecal patch transplantation for patients who have undergone prior total laryngectomy. Two women received ileocaecal patch transplantation for secondary voice restoration after total laryngectomy. In order to make the tracheoesophageal shunt for speech, a new orifice on the anterior wall of the hypopharynx had to be opened, which was closed at the time of laryngectomy. The hypopharyngeal orifice was covered by a free caecal patch harvested from an ileocaecal segment. Then, a tracheoesophageal shunt was created by anastomosing the terminal ileum of the patch and the remnant of the cervical trachea. Expiratory air was diverted into the pharynx through the ileum of the transplanted graft when the tracheostoma was closed by digital occlusion. Aspiration through an oesophagotracheal shunt in swallowing was prevented by the ileocaecal valve on the patch. Both patients began to speak up to 4 weeks after surgery without requiring training or difficult practice to achieve initial phonation and to be able to swallow without aspiration. The advantages of our procedure are (1) it can be carried out at the time of laryngectomy and also at secondary voice restoration after earlier laryngectomy; (2) the graft contains an ileocaecal valve that prevents aspiration through the shunt and also functions as a vibrating device to produce voice; (3) our procedure can be adapted to individuals whose tracheostoma is detached from the oesophagus and becomes contraindicated for a voice prosthesis. We believe that our newly designed procedure is a unique and useful alternative, especially for secondary voice restoration after prior total laryngectomy.

Mutations that are synthetically lethal with a gas1Delta allele cause defects in the cell wall of Saccharomyces cerevisiae.

The GAS1-related genes of fungi encode GPI-anchored proteins with beta-1,3-glucanosyltransferase activity. Loss of this activity results in defects in the assembly of the cell wall. We isolated mutants that show a synthetic defect when combined with a gas1Delta allele in Saccharomyces cerevisiae, and identified nine wild-type genes that rescue this defect. The indispensability of BIG1 and KRE6 for the viability of gas1Delta cells confirmed the important role of beta-1,6-glucan in cells that are defective in the processing of beta-1,3-glucan. The identification of the Wsc1p hypo-osmotic stress sensor and components of the PKC signal transduction pathway in our screen also confirmed that the cell wall integrity response attenuates the otherwise lethal gas1Delta defect. Unexpectedly, we found that the KEX2 gene is also required for the viability of the gas1Delta mutant. Kex2p is a Golgi/endosome-membrane-anchored protease that processes secretory preproteins. A cell wall defect was also found in the kex2Delta mutant, which was suppressible by multiple copies of the MKC7 or YAP3 gene, both of which encode other GPI-anchored proteases. Therefore, normal cell wall assembly requires proteolytic processing of secretory preproteins. Furthermore, the genes CSG2 and IPT1 were found to be required for normal growth of gas1Delta cells in the presence of 1 M sorbitol. This finding suggests that complex sphingolipids play a role in the hyper-osmotic response.