Atsushi Nonaka

Small carcinoma of the pancreas. Clinical and pathologic evaluation of 17 patients.

The clinical and pathologic characteristics of 17 small carcinomas (less than 2 cm in diameter) of the pancreas are reviewed in this article. All the tumors were located in the head of the pancreas, and the clue to the diagnosis was jaundice in ten patients and abdominal pain in seven. Carcinoembryonic antigen (CEA) and CA 19‐9 were not reliable markers for detecting small carcinomas of the pancreas. Ultrasonography (US), computerized tomography (CT), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP) were useful diagnostic tools. Lymph node metastases were found in 41% of affected patients, capsular invasion in 24%, retroperitoneal invasion in 24%, and portal system involvement in 29%. In five patients the carcinoma was Stage I; in eight patients, Stage II; in two patients, Stage III, and in two patients, Stage IV. Fifteen patients with Stages I to III and one patient with Stage IV underwent curative pancreaticoduodenectomy or total pancreatectomy, and one patient with liver metastasis and Stage IV underwent noncurative pancreaticoduodenectomy. The cumulative 4‐year survival rate was 37%. Although four patients with Stage I disease lived for more than 48 months, the survival period of the 12 patients with Stages II to IV disease was less than 25 months. Thus, small carcinoma of the pancreas is not always curable; however, a small, localized lesion without any extratumoral extension can be resected with a chance of cure.

Macular Ganglion Cell Layer Imaging in Preperimetric Glaucoma with Speckle Noise–Reduced Spectral Domain Optical Coherence Tomography

OBJECTIVE To visualize the macular ganglion cell layer (GCL) and measure its thickness in normal eyes and eyes with preperimetric glaucoma, using speckle noise-reduced spectral domain optical coherence tomography (SD-OCT). DESIGN Retrospective consecutive case series. PARTICIPANTS Thirty-seven eyes of 37 patients with preperimetric glaucoma and 39 normal eyes of 39 volunteers. METHODS Vertical and horizontal SD-OCT B-scan images were acquired with minimal speckle noise by using eye-tracking to obtain and average 50 B-scans at each identical location of interest. B-scan images were manually analyzed for GCL, retinal nerve fiber layer (RNFL), and inner plexiform layer shapes and thicknesses in the macula. MAIN OUTCOME MEASURES Macular GCL images and thickness in normal eyes and in eyes with preperimetric glaucoma. RESULTS The macular GCL was clearly seen on speckle noise-reduced SD-OCT images in normal eyes and eyes with preperimetric glaucoma. In each eye with preperimetric glaucoma, thinning of the macular GCL was visually apparent, particularly on vertical scans. The mean regional macular GCL was most severely thinned in the inferior perifoveal region, where its thickness was <70% of its normal thickness in 30 (81.1%) of the 37 eyes and <50% of its normal thickness in 13 (35.1%) of the 37 eyes. When the sensitivity and specificity for detecting abnormal thinning (outside the lower limit of 99% confidence interval [CI] for the means in the 39 normal eyes) in at least one 0.5-mm segment or sector were compared, the macular GCL on vertical B-scans exhibited higher sensitivity (81.1%) than the other layers on vertical B-scans (99% CI, 5.4%-59.5%; P = 0.00075-0.02100), the macular GCL (99% CI, 40.5%; P = 0.00027) on horizontal B-scans, the other layers (99% CI, 5.4%-48.6%; P<0.00048-0.00400) on horizontal B-scans, and circumpapillary RNFL automatically measured on SD-OCT (54.1%; P = 0.021), and scanning laser polarimetry with variable corneal compensation (24.3%; P = 0.00095). All the macular layers on both the vertical and horizontal B-scans and circumpapillary RNFL thickness exhibited comparable specificity (91.4-100.0%, statistically not different). CONCLUSIONS Speckle noise-reduced SD-OCT imaging allowed clear visualization and measurement of the macular GCL, which was severely thinned in eyes with preperimetric glaucoma. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Changes of Xanthine Oxidase, Lipid Peroxide and Superoxide Dismutase in Mouse Acute Pancreatitis

The role of free radicals in the development of pancreatitis was evaluated by measuring the level of activities of xanthine oxidase (XOD), lipid peroxide (LPO) and superoxide dismutase (SOD). Acute pancreatitis was induced in female mice fed a choline-deficient meal containing 0.5% DL-ethionine (CDE meal). Acute pancreatitis was confirmed by the changes in serum amylase level and other typical features observed microscopically 24 h after the meal was taken. Activity of XOD was elevated significantly (p less than 0.05) from the baseline of 1.13 +/- 0.19 U/g tissue to 2.34 +/- 0.46, 2.59 +/- 0.33 and 3.46 +/- 0.70 U/g tissue, 8, 12 and 24 h, respectively, after the CDE meal. The LPO level was also increased from an undetectable amount to 1.10 +/- 0.47 nmol/ml (p less than 0.05), 1.03 +/- 0.18 (p less than 0.01) at 6 and 8 h, respectively, and then returned to an undetectable amount at 12 h. The peak level of LPO was shown at 24 h, 1.76 +/- 0.40 nmol/ml (p less than 0.01) and gradually decreased until 48 h, 1.17 +/- 0.37 nmol/ml (p less than 0.01) after the CDE meal. Changes of LPO took a biphasic pattern. SOD was decreased significantly from 47.1 +/- 3.4 mU/g tissue to 30.7 +/- 2.5, 24.8 +/- 1.7 and 20.6 +/- 1.1 mU/g tissue at 8 (p less than 0.01), 12 (p less than 0.01), and 24 (p less than 0.01) h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in Lipid Peroxide and Oxygen Radical Scavengers in Cerulein-Induced Acute Pancreatitis

The role of free radicals in the development of cerulein-induced pancreatitis was evaluated by measuring the activity of the endogenous scavengers, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHpx), as indicators of the defense system, and the level of lipid peroxide (LPO) in the pancreas, as an indicator of the offense system. Acute pancreatitis was induced by 5 hourly intraperitoneal administrations of cerulein (50 micrograms/kg body weight), in 0.9% NaCl, to mice. The presence of acute pancreatitis was confirmed by changes in serum amylase levels and in typical microscopical features. Regarding the changes in the levels of endogenous scavengers, the SOD level was decreased significantly from a basal level of 52.6 +/- 3.94 to 43.1 +/- 2.79 mU/micrograms DNA at 6 h (p less than 0.01) to 38.8 +/- 5.18 mU/micrograms DNA at 9 h (p less than 0.05) and to 31.7 +/- 3.10 mU/micrograms DNA at 12 h (p less than 0.01) after the first intraperitoneal cerulein injection. The CAT level also decreased significantly from a basal level of 7.80 +/- 0.27 to 5.86 +/- 0.46 mU/micrograms DNA at 9 h (p less than 0.01) and to 4.52 +/- 0.21 mU/microgram DNA at 12 h (p less than 0.01). GSHpx increased from a basal level of 6.80 +/- 0.43 to 7.58 +/- 0.50 mU/micrograms DNA at 9 h and to 10.2 +/- 0.52 mU/micrograms DNA at 12 h after the first intraperitoneal cerulein injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of localized retinal nerve fiber layer defects in glaucoma using enhanced spectral-domain optical coherence tomography.

OBJECTIVE To compare retinal nerve fiber layer (RNFL) defects on fundus photographs with circumpapillary RNFL (cpRNFL) thinning or disruption on images obtained by speckle-noise-reduced spectral-domain optical coherence tomography (enhanced SD OCT), single-scan SD OCT, and single-scan time-domain OCT (TD OCT). DESIGN Retrospective, comparative case series. PARTICIPANTS Forty-four eyes of 44 patients with open-angle glaucoma with localized, wedge-shaped RNFL defects on red-free photographs and 35 normal eyes of 35 volunteers. METHODS Cross-sectional images of the cpRNFL and cpRNFL thinning, compared with the confidence interval limit of the normative database where the RNFL defect was photographically identified, were compared between the 3 types of OCT instruments: enhanced SD OCT (SD OCT with eye tracking and averaging of 16 images at the same location to reduce speckle noise; Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany), single-scan SD OCT (RTVue-100; Optovue, Fremont, CA), and single-scan TD OCT (Stratus; Carl Zeiss-Meditec, Dublin, CA). MAIN OUTCOME MEASURES Cross-sectional images of localized RNFL defects on red-free fundus photographs, sensitivity for detecting the photographic RNFL defect, and sensitivity and specificity for detecting glaucoma as having at least 1 abnormally thinned sector on the cpRNFL thickness map on OCT. RESULTS Among the 44 eyes with glaucoma, 65 RNFL defects were identified on red-free fundus photographs. The cpRNFL boundaries were clearer on enhanced SD OCT images than on single-scan SD OCT or TD OCT images, particularly in regions corresponding to the RNFL defects. Enhanced SD OCT revealed various degrees of cpRNFL thinning, and disruption of cpRNFL reflectivity was seen in the same location as the photographic RNFL defect for 23 (35.4%) of the 65 RNFL defects. The RNFL defects were significantly less likely to be detected by single-scan TD OCT or SD OCT (P = 0.002 and P = 0.006, respectively) when the RNFL was not disrupted. Enhanced SD OCT was more sensitive in detecting the RNFL defects that were not disrupted compared with single-scan TD OCT (P<0.0001) or SD OCT (P<0.0001). Enhanced SD OCT had better sensitivity and specificity for detecting glaucoma compared with single-scan TD OCT or SD OCT (sensitivity, P = 0.006 and P = 0.001; specificity, P = 0.001 and P = 0.004, respectively). CONCLUSIONS These results suggest that speckle-noise reduction can improve the detection of photographic RNFL defects in which cpRNFL reflectivity on OCT images is not disrupted. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

High-Resolution Imaging of Retinal Nerve Fiber Bundles in Glaucoma Using Adaptive Optics Scanning Laser Ophthalmoscopy

PURPOSE To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO). DESIGN Prospective cross-sectional study. METHODS Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system. RESULTS The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P < .001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P < .001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017). CONCLUSIONS AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function.

Wide 3-dimensional macular ganglion cell complex imaging with spectral-domain optical coherence tomography in glaucoma.

PURPOSE To determine whether measurement of ganglion cell complex (GCC) thickness over a wide area (8-mm diameter) can improve the glaucoma-discriminating ability of spectral-domain optical coherence tomography (SD-OCT) compared to that in the standard macular area (6-mm diameter). METHODS Ninety-three subjects were enrolled, including 46 healthy eyes of 46 volunteers and 47 eyes of 47 glaucoma patients (23 eyes with preperimetric glaucoma [PPG] and 24 eyes with early glaucoma [EG]). All patients underwent SD-OCT raster scanning over a 9 mm × 9 mm square area centered on the fovea. Areas under the receiver operating characteristic curves (AROCs) were compared between wide sector (1-8-mm ring) and standard-size sector (1-6-mm ring) charts. RESULTS AROCs for average GCC thickness in the wide chart were significantly greater than those of the standard chart in eyes with PPG (0.928 vs. 0.891; P = 0.038), EG (0.912 vs. 0.861; P = 0.003), and both (0.920 vs. 0.876; P = 0.004). Overall, the AROCs of regional GCC thicknesses were nearly comparable between the middle ring (4-6 mm) and outer ring (6-8 mm). Coefficients of variation were 0.68% and 0.97% in the standard and wide sector charts, respectively, in eyes with PPG, and 0.45% and 0.72% in the standard and wide sector charts, respectively, in eyes with EG. CONCLUSIONS Addition of the GCC thickness outside the macula to the standard macular GCC thickness significantly increased the glaucoma-discriminating ability of SD-OCT.

Peripapillary scleral deformation and retinal nerve fiber damage in high myopia assessed with swept-source optical coherence tomography.

PURPOSE To study peripapillary morphologic changes in highly myopic eyes using swept-source optical coherence tomography at a longer wavelength. DESIGN Prospective cross-sectional study. METHODS Peripapillary regions of 196 eyes of 107 patients with high myopia (refractive error, <-8.0 diopters or axial length, >26.0 mm) were analyzed quantitatively and qualitatively with an swept-source optical coherence tomography prototype system that uses a tunable laser light source operated at a 100,000-Hz A-scan repetition rate in the 1-μm wavelength region. The visual field was evaluated by standard automated perimetry. Area of peripapillary atrophy β and presence of scleral protrusion temporal to the optic disc were assessed. RESULTS Peripapillary atrophy β area, but not disc area, was significantly larger in eyes with visual field defect (3.16 ± 2.70 mm(2); range, 0.00 to 12.85 mm(2)) than those without visual field defect (2.31 ± 2.83 mm(2); range, 0.00 to 17.70 mm(2)). Temporal scleral protrusion was detected by color stereo disc photography in 22 (19.5%) of 113 eyes with visual field defect and in 4 (4.8%) of 83 eyes without visual field defect. Scleral bending demonstrated a wide range of angles (mean, 31.0 ± 21.1 degrees; range, 2 to 80 degrees). The angle of scleral bending, but not the distances from scleral bend to disc margin or foveal center, correlated significantly with retinal nerve fiber layer thickness above the bend (r = -0.557, P = .007) and visual field defect severity (r = -0.445, P = .038). CONCLUSIONS Swept-source optical coherence tomography visualizes peripapillary deep structures in high myopia. Some cases of high myopia may be affected by direct scleral compression or stretching at the peripapillary region.

Evidence for a role of free radicals by synthesized scavenger, 2-octadecylascorbic acid, in cerulein-induced mouse acute pancreatitis

To define the role of free radicals and of lipid peroxide involvement during the progress of cerulein-induced acute pancreatitis in mice, we evaluated the effect of a novel free radical scavenger, 2-octadecylascorbic acid (CV-3611), on pancreatic edema formation, and the levels of serum enzymes (amylase, lipase) and of lipid peroxide in pancreatic tissue. Mice were divided into three groups: control group, intraperitoneal injection of saline only; pancreatitis group, cerulein 50 μg/kg injected intraperitoneally six times at 1-hr intervals; treatment group, CV-3611 10 mg/kg subcutaneously just after intraperitoneal cerulein injection. After the cerulein injection, the degree of pancreatic edema formation, serum amylase and lipase levels, and the amount of lipid peroxide in pancreatic tissue increased significantly during the observation period of 12 hr. Treatment with CV-3611 resulted in significant reduction in pancreatic edema formation at 3.5 hr (P<0.05) and 9 hr (P<0.05), serum amylase and lipase levels at 3.5 hr (P<0.05) and 12 hr (P<0.05), and lipid peroxide levels at 3.5 hr (P<0.05), 6 hr (P<0.05) and 12 hr (P<0.05). These results indicate that a novel free radical scavenger, CV-3611, has a strong therapeutic effect during the development of acute pancreatitis and suggest that oxygenderived free radicals play an important role in the pathogenesis of acute pancreatitis.

Frequency-doubling technology and retinal measurements with spectral-domain optical coherence tomography in preperimetric glaucoma.

BackgroundTo determine the relationship between visual fields and retinal structures measured with spectral-domain optical coherence tomography in preperimetric glaucoma (PPG).MethodsTwenty-six eyes of 26 patients with PPG and 20 healthy eyes of 20 volunteers were included. All patients underwent Heidelberg retina tomography-2 (HRT2), standard automated perimetry (SAP), frequency-doubling technology (FDT) perimetry, and RTVue-100. SAP and FDT indices, HRT parameters, and circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) thicknesses were correlated using Pearson’s test. Areas under the receiver operating characteristic curves (AUROCs) and sensitivity/specificity based on each parameter’s definition of abnormalities were compared between parameters.ResultsSignificant differences were found in FDT-MD, FDT-PSD, SAP-PSD, cpRNFL, and mGCC parameters (p < 0.001–0.015), but not in SAP-MD or HRT parameters, between PPG and control groups. Significant correlations were not found between visual field indices and structural parameters, except between FDT-MD and HRT rim area (r = 0.450, p = 0.021) and between FDT-PSD and temporal cpRNFL thickness (r = 0.402, p = 0.021). AUROCs for cpRNFL (p = 0.0047–0.033) and mGCC (p = 0.0082–0.049) parameters were significantly better than those of HRT parameters, whereas significant differences were not found between FDT indices and cpRNFL or mGCC parameters or between cpRNFL and mGCC parameters. Adding average cpRNFL or mGCC thickness to FDT-MD significantly increased sensitivity compared to single parameters (p = 0.016–0.031).ConclusionsStructural and functional parameters were poorly correlated but complementary for glaucoma detection in PPG. Combining these parameters may improve PPG diagnosis.