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It is widely known that the spectral shapes of light sources, represented by FWHM or E95 conventionally, have great impacts on the optical lithography performances. On the other hand, modern optical lithography requires more precise control of Critical Dimension (CD). Of the many factors impact the CD, OPE and Process Window (PW) play important roles in optical lithography. The Gigaphoton’s Spectral Engineering (SE) technique introduced in its latest light sources, which can generate a variety of spectral shapes, such as, top-hat spectra, multi-peak spectra in addition to conventional broadband spectra, can have substantial contributions to both PW enhancements as well as OPE optimizations. In the last report, as an example, we have shown that the PW of CH/VIA will be improved by the introduction of SE technique. However, the PW improvement is realized mainly by expanding DOF at the cost of EL. As users are interested in CD Uniformity (CDU), not PW itself, and the CDU depends on both focus and dose accuracies, a question that is likely to arise is, will the CDU be improved by the SE? In this report, we are going to show that, by the introduction of SE, users can expect significant improvements of CDU for semi-isolated or isolated patterns, at trivial costs of CDU deteriorations for dense patterns. For the OPE, although it is widely known that spectral width can be used in OPE tunings, but it has rarely been used in FABs, as a tuning knob. We are going to show that the spectral width control with SE will greatly improve both qualities and chances of OPE tunings.

DUV lightsources used in lithography process is enabling to shrink the feature size as a driver for Moore’s Law in order to make semiconductor devices to a new level. Multi-patterning processes has been applied to break through the ArFi resolution limit. These processes require the pattern fidelity and placement accuracy.We have studied an impact of bandwidth distribution and asymmetry by imaging simulation. The results show the bandwidth shape and asymmetry cause a change in the CD. Our study shows that Gigaphoton‘s latest light source can contribute to improvements of fidelity and EPE.

Chipmakers have used cross-platform of both EUV exposure and ArF immersion multi-patterning exposure depending on cost effectiveness at each layer. ArF immersion exposure has been required lower linewidth roughness(LWR) to reduce cross matched machine overlay(xMMO) which is the overlay between the different platforms. ArF light sources essentially produce speckle as non-uniform intensity distribution resulting from interference effects generated within a beam. It leads to increase LWR, which results in increasing xMMO. The latest ArF immersion light source, GT66A is introduced a new optical pulse stretcher(OPS) that increases pulse duration to reduce speckle by 30% to improves LWR, which reduces xMMO. This technology will improve chip yield for chipmakers in the processes mixed ArF immersion exposure and EUV exposure.

Any new lithographic technology to be introduced into manufacturing must deliver either a performance advantage or a cost advantage. Key technical attributes include alignment, overlay and throughput. In this work, we review progress on pattern capability, throughput, mask life and overlay.

As the most aggressive features in advanced memory designs continue to shrink, so does the overlay budget. The number of layer stacks also creates unwanted topography, and the alignment robustness of lithography tools becomes much more important for on-product overly. Canon developed a through-the-mask moire alignment system for the FPA-1200NZ2C nanoimprint lithography (NIL) system allowing high-speed measurement of several alignment marks within each imprint field and alignment compensation to be completed during the imprinting sequence. To provide increased process flexibility and overlay accuracy while maintaining high-productivity, we have developed a new low-noise and high-resolution moire diffraction alignment system based on spatial phase interferometry. In this paper, we report on the TTM detection system used in FPA-1200NZ2C. In particular, the principle of moire detection and the improvement of the detection method will be described. The measurement error of moire is analyzed by a simplified model calculation and we confirmed the relationship between process change and alignment error. Results of analyses proved that selection of the wavelength are key factors for optimizing alignment accuracy. Based on these results we applied the following improvement items: 1) Dual Dipole illumination, 2) Optimization of the alignment wavelength. We evaluated the new alignment system measurement error by comparing the moire measurement value with the measured overlay values for 24 wafers and confirmed that new TTM alignment system can reduce to the measurement error more than 40%. The data shows that our moire measurement system can provide process robustness and can support mass-production of leading-edge memory products.

Nanoimprint lithography (NIL) techniques are known to possess replication resolution below 5nm. A specific form of imprint lithography using jetted resist has been developed for manufacturing advanced CMOS memory. Canon’s NIL process involves field-by-field inkjet deposition of a low viscosity resist fluid followed by imprinting with nano-scale precision overlay. A mask with a relief structure is lowered into the fluid which then quickly flows into the relief patterns in the mask by capillary action. Following this filling step, the resist is crosslinked under UV radiation, and then the mask is separated from the substrate leaving a patterned resist on the substrate. The technology faithfully reproduces patterns with a higher resolution and greater uniformity compared to those produced by photolithography equipment. Additionally, as this technology does not require an array of wide-diameter lenses and the expensive light sources necessary for advanced photolithography equipment, NIL equipment achieves a simpler, more compact design, allowing for multiple units to be clustered together for increased productivity. Previous studies have demonstrated NIL resolution better than 10nm, making the technology suitable for the printing of several generations of critical memory levels with a single mask. In addition, resist is applied only where necessary, thereby eliminating material waste. Given that there are no complicated optics in the imprint system, the reduction in the cost of the tool, when combined with simple single level processing and zero waste leads to a cost model that is very compelling for semiconductor memory applications. Any new lithographic technology to be introduced into manufacturing must deliver either a performance advantage or a cost advantage. Key technical attributes include alignment, overlay and throughput. In previous papers, overlay and throughput results have been reported on test wafers. In this work, improvements to the alignment system, together with the High Order Distortion Correction (HODC) system have enabled better distortion and overlay results on both test wafers and device wafers. The linear response of the HODC system was demonstrated for multiple high order terms and on test wafers, XMMO of 2.9nm and 3.2nm in x and y respectively was achieved. Additionally an SMO of 2.2nm and 2.4nm was achieved, with an opportunity to further improve results by applying wafer chucks with better flatness specifications.

Imprint lithography is an effective and well known technique for replication of nano-scale features. Nanoimprint lithography (NIL) manufacturing equipment utilizes a patterning technology that involves the field-by-field deposition and exposure of a low viscosity resist deposited by jetting technology onto the substrate. The patterned mask is lowered into the fluid which then quickly flows into the relief patterns in the mask by capillary action. Following this filling step, the resist is crosslinked under UV radiation, and then the mask is removed, leaving a patterned resist on the substrate. The technology faithfully reproduces patterns with a higher resolution and greater uniformity compared to those produced by photolithography equipment. Additionally, as this technology does not require an array of widediameter lenses and the expensive light sources necessary for advanced photolithography equipment, NIL equipment achieves a simpler, more compact design, allowing for multiple units to be clustered together for increased productivity. Previous studies have demonstrated NIL resolution better than 10nm, making the technology suitable for the printing of several generations of critical memory levels with a single mask. In addition, resist is applied only where necessary, thereby eliminating material waste. Given that there are no complicated optics in the imprint system, the reduction in the cost of the tool, when combined with simple single level processing and zero waste leads to a cost model that is very compelling for semiconductor memory applications. Any new lithographic technology to be introduced into manufacturing must deliver either a performance advantage or a cost advantage. Key technical attributes include alignment, overlay and throughput. In previous papers, overlay and throughput results have been reported on test wafers. In this work, improvements to the alignment system, together with the High Order Distortion Correction (HODC) system have enabled better distortion and overlay results on both test wafers and device wafers. On test wafers, XMMO of 2.9nm and 3.2nm in x and y respectively was demonstrated. SMO of 2.2nm and 2.4nm was achieved, with an opportunity to further improve results by applying wafer chucks with better flatness specifications. Comparable results were also achieved on device wafers by applying a multi-wavelength alignment strategy and a feed forward strategy to realize align signal convergence within the allocated 0.60 second budget.

We describe a case of serum amyloid A (SAA) and C-reactive protein (CRP) positive nodule detected by immunohistochemical analysis in a 37-year-old woman with alcohol-related cirrhosis. Imaging studies at first admission pointed to hepatocellular carcinoma (HCC), a dysplastic nodule, an inflammatory pseudotumor or focal nodular hyperplasia (FNH). Ultrasonography-guided biopsy in Segment 2 showed minimal atypical changes, except for a slight increase in cell density and micronodular cirrhosis in the non-nodular portion. gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging carried out after a year and a half revealed hypervascularity in the arterial phase and isointensity in the hepatobiliary phase. Three years thereafter, however, the imaging displayed a change from isointensity to a defect in the hepatobiliary phase, and the nodule demonstrated minimal histological atypia. Immunohistochemical staining of the nodule was positive for SAA, CRP, liver fatty acid-binding protein and glutamine synthetase, but negative for β-catenin, heat shock protein 70 and Glypican 3. Organic anion transporter (OATP)8 staining was weaker in the nodule than in the non-nodular portion of the alcohol-related micronodular cirrhosis. The nodule was diagnosed as an SAA and CRP positive nodule, and HCC was ruled out. Despite the change from isointensity to a defect in the hepatobiliary phase, no evidence of HCC was found in the biopsy specimen. The change may be explained more by the weak OATP8 staining compared with that of alcohol-related liver cirrhosis than by malignant transformation into HCC.

Ultrasound using microbubble-based contrast agents is useful for vascular imaging. Directional eFLOW (D-eFLOW) is a novel technology for vascular assessment that provides high spatial and temporal resolution. The purpose of this study was to investigate the utility of endoscopic ultrasound (EUS)-guided D-eFlow before and after administration of an ultrasound contrast agent (USCA) for assessing the vascularity of solid pancreatic lesions. D-eFlow was compared to power Doppler EUS (PD-EUS) or color Doppler EUS (CD-EUS) before and after USCA injection. We also evaluated the Visual Vascular Assessment (ViVA) scale for the estimation of vascularity and investigated its reliability using the interclass correlation coefficient (ICC). From January 2007 to March 2007, 35 patients (mean age, 64.5 years old; age range, 28–81 years) underwent EUS followed by D-eFLOW EUS, PD-EUS, and CD-EUS before and after administration of USCA. The pancreatic parenchymal ViVA score, pancreatic vascular pattern, and ICC were evaluated for all lesions. Concerning the sensitivity for detection of the hypovascular pattern in pancreatic adenocarcinoma, D-eFLOW (before and after USCA) had similar sensitivity to PD-EUS (before and after USCA) and CD-EUS (before and after USCA). D-eFLOW after contrast showed the highest accuracy (82.3 %) and negative predictive value (53.8 %) among all the modalities investigated. There was a good correlation among the ViVA scores for D-eFLOW before contrast, those for D-eFLOW EUS, and those for PD-EUS and CD-EUS. The reliability of the ViVA scale was excellent with an ICC of 0.81. In conclusion, D-eFLOW EUS is a sensitive, reliable, and highly accurate method of assessment of pancreatic vascularity. D-eFLOW EUS with contrast was more sensitive than PD-EUS and CD-EUS for assessment of pancreatic vascularity.

Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS), a novel technology, visualizes parenchymal perfusion in the pancreas. This study prospectively evaluated how accurately CH-EUS characterizes pancreatic lesions and compared its diagnostic ability with that of contrast-enhanced multidetector-row computed tomography (MDCT) and endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA).A total of 277 consecutive patients with pancreatic solid lesions that were detected by conventional EUS underwent CH-EUS for evaluation of vascularity. After infusing an ultrasound contrast, CH-EUS was performed by using an echoendoscope and a specific mode for contrast harmonic imaging. On the basis of the intensity of enhancement, the lesions were categorized into four patterns: nonenhancement, hypoenhancement, isoenhancement, and hyperenhancement. For comparison, all patients underwent MDCT. The ability of CH-EUS to differentiate ductal carcinomas from the other solid tumors, particularly small lesions (≤2 cm in diameter) was assessed, and compared with the differentiating abilities of MDCT and EUS-FNA.In terms of reading the CH-EUS images, the κ-coefficient of the interobserver agreement test was 0.94 (P0.001). CH-EUS-depicted hypoenhancement diagnosed ductal carcinomas with a sensitivity and specificity of 95.1% (95% confidence interval (CI) 92.7-96.7%) and 89.0% (95% CI 83.0-93.1%), respectively. For diagnosing small carcinomas by CH-EUS, the sensitivity and specificity were 91.2 % (95% CI 82.5-95.1%) and 94.4% (95% CI 86.2-98.1%), respectively. CH-EUS-depicted hypervascular enhancement diagnosed neuroendocrine tumors with a sensitivity and specificity of 78.9% (95% CI 61.4-89.7%) and 98.7% (95% CI 96.7-98.8%), respectively. Although CH-EUS and MDCT did not differ significantly in diagnostic ability with regard to all lesions, CH-EUS was superior to MDCT in diagnosing small (≤2 cm) carcinomas (P0.05). In 12 neoplasms that MDCT failed to detect, 7 ductal carcinomas and 2 neuroendocrine tumors had hypoenhancement and hyperenhancement on CH-EUS, respectively. When CH-EUS was combined with EUS-FNA, the sensitivity of EUS-FNA increased from 92.2 to 100%.CH-EUS is useful for characterizing conventional EUS-detected solid pancreatic lesions. EUS equipped with contrast harmonic imaging may play an important role in the characterization of small tumors that other imaging methods fail to depict and may improve the diagnostic yield of EUS-FNA.

Although endoscopic ultrasonography (EUS) has the advantage over other imaging methods in that it is possible to obtain high resolution images of the pancreas, it is limited in its ability to characterize pancreatic masses. Contrast-enhanced power Doppler ultrasonography suffers from several limitations such as blooming artifacts, poor spatial resolution, low sensitivity to slow flow and high sensitivity to motion artifacts. Recently, EUS system specific for contrast harmonic imaging has been developed. The use of this EUS system enabled us to observe images of microcirculation and parenchymal perfusion without Doppler-related artifacts in the pancreas. Contrast-enhanced harmonic EUS could diagnose pancreatic carcinomas as hypovascular masses with a high sensitivity (89-96%) and specificity (64-88%). Contrast-enhanced harmonic EUS also discriminates mural nodules from mucous clots in the intraductal papillary mucinous neoplasms.

Abdominal pain in patients with pancreatic cancer is a common symptom that is often difficult to manage. Opioids are frequently used in an attempt to mitigate pain; however, side effects may develop. Celiac plexus neurolysis (CPN) affords effective pain control in patients with pancreatic cancer and is not associated with opioid side effects. Endoscopic ultrasound (EUS)-guided CPN has demonstrated safety and efficacy due to real-time imaging and anterior access to the celiac plexus from the posterior gastric wall, thereby avoiding complications related to the puncture of spinal nerves, arteries and the diaphragm, and is now practiced widely. Furthermore, two new techniques of EUS-guided neurolysis for abdominal pain management in pancreatic cancer patients have recently been developed. The first technique is EUS-guided celiac ganglia neurolysis (EUS-CGN) in which EUS facilitates CGN by enabling direct injection into the individual celiac ganglion, and the second technique is EUS-guided broad plexus neurolysis (EUS-BPN) which extends over the superior mesenteric artery. This review provides evidence for the efficacy of EUS-CPN. Particular attention is paid to the two new techniques of EUS-guided neurolysis, EUS-CGN and EUS-BPN.

Background and Aims: Double-filtration plasmapheresis (DFPP) together with interferon (IFN) administration produces a substantial reduction in the viral load during the early stages of treatment. Methods: Based on their responses to previous pegylated IFN and ribavirin (PEG-IFN/RBV) therapy, 20 patients were divided into null virological response (NVR; n = 12) and relapse (n = 8) groups. DFPP was used in combination with IFN-β/RBV with subsequent administration of PEG-IFN-α2a/RBV therapy (DFPP + IFN-β/RBV then PEG-IFN/RBV). Early viral dynamics was assessed, focusing especially on complete early virological response (cEVR) associated with sustained virological response. Additionally, the interleukin 28B gene, the IFN/RBV resistance-determining region, the IFN sensitivity-determining region and the core regions were analyzed. Results: Rapid virological response was achieved in 0% (0/12) of NVR and in 75% (6/8) of relapse patients, with a significant difference between the two groups (p = 0.001). Similarly, cEVR was achieved in 8% (1/12) of NVR and in 88% (7/8) of relapse patients, with a significant difference between the two groups (p = 0.037). By multivariate logistic regression analysis, interleukin-28B major was a significant determiner of cEVR (odds ratio = 24.19, p = 0.037). Conclusion: DFPP + IFN-β/RBV then PEG-IFN/RBV therapy is indicated more for relapse than for NVR patients.

The diagnosis of intra-abdominal lesions of undetermined origin is often a challenge for endoscopists and radiologists.To evaluate the microvasculature of benign and malignant intra-abdominal lesions by contrast-enhanced harmonic EUS (CEH-EUS) and to investigate its usefulness for discriminating between malignant and benign lesions.The vascularity of intra-abdominal lesions of undetermined origin was observed by using CEH-EUS. The lesions were classified according to their vascular patterns. The effectiveness of CEH-EUS in differentiating malignant from benign lesions was evaluated.Kinki University School of Medicine, Osaka, Japan.Forty-three patients, each with a lesion of undetermined origin, were evaluated prospectively by CEH-EUS between March 2007 and March 2009.CEH-EUS was performed by using a prototype echoendoscope and the extended pure harmonic detection mode (a specific mode for contrast harmonic imaging).The lesions were categorized by 2 physicians as having no, homogeneous, or heterogeneous enhancement. A consensus was reached for each case offline. How the benign and malignant groups differed in terms of their enhancement patterns was examined.The kappa coefficient of the interobserver agreement test was 0.953 (P.001). Of the 27 malignant lesions, 26 (96.3%) exhibited heterogeneous enhancement. The 1 remaining malignant lesion (3.7%) showed homogeneous enhancement. Of the 16 benign lesions, none displayed heterogeneous enhancement, and 12 (75%) and 4 (25%) exhibited homogeneous and no enhancement, respectively. The malignant and benign lesion groups differed significantly in terms of homogeneous and heterogeneous enhancement (P.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy with which CEH-EUS differentiated malignant from benign lesions were 96.3%, 100%, 100%, 94.1%, and 97.6%, respectively.A single medical unit with a limited number of patients.CEH-EUS depicted the microvasculature of intra-abdominal lesions of undetermined origin very clearly and may be useful for characterizing such lesions.

PIVKA II産生胃癌の報告は稀である.今回肝転移を伴ったPIVKA II産生胃癌の1例を経験したので若干の文献的考察を加え報告する.症例は77歳,男性. 2004年7月の検診で胸部大動脈瘤を指摘され9月10日に当院を受診した. CT検査で胸部大動脈瘤以外に肝S6に腫瘍も認めたため,消化器臓器も精査した.血液検査でHCV抗体陽性を認めるも,肝機能異常は認めなかった.また腫瘍マーカーはAFP, PIVKA IIのみ上昇を認めた.上部消化管内視鏡検査で胃幽門後壁に3型様腫瘍を認め,胃生検検査でAFP産生胃癌と診断された.術前診断はAFP産生胃癌と,転移性または原発性肝癌と考え11月2日に幽門側胃切除術と肝右葉切除術を行った.病理学的診断は胃,肝腫瘍ともに管状組織と胞巣状増殖から構成される腺癌であった.また免疫染色ではAFP, PIVKA II染色ともに陽性であったため, PIVKA IIおよびAFP産生胃癌と診断した.

胆嚢未分化癌は比較的稀で,極めて予後不良とされる.今回われわれは胆嚢未分化癌の1例を経験したので報告する.症例は51歳,女性. 2004年3月31日に発熱,右季肋部痛を認め当院に入院した.画像検査で胆嚢体部に4cm大の辺縁整,境界明瞭な腫瘍を認めた.胆嚢癌とそれに伴う胆嚢炎と診断し保存的治療を行うも症状の改善を認めず.徐々に貧血,肝機能異常が出現したため, 5月15日に全層切除を伴った胆嚢摘出術および1群までのリンパ節郭清を行った.腫瘍は漿膜下層まで浸潤していたがリンパ節転移,脈管転移は認めなかった.病理所見より腫瘍は紡錘細胞からなり,腫瘍中心部は壊死していた.サイトケラチン陽性,ピメンチン陰性で胆嚢未分化癌と診断した.術後は追加手術を行わず,抗癌剤のみで治療を行った.術後17カ月の現在,再発の徴候はみられていない.

症例は69歳,女性. 1997年6月より貧血,肝血管腫と診断され経過観察されていた. 2000年6月に肝血管腫の増大と新たな肝腫瘍を指摘され入院となった.入院時に便潜血陽性を認め,上部,下部消化管内視鏡検査を行うも異常を認めなかった.肝腫瘍に対し針生検を行い肝細胞癌が疑われ, 9月12日に手術を施行した.術中,回腸に2cm大の腫瘍を認め,回腸部分切除と肝切除術を施行した.病理診断は,小腸カルチノイドとその肝転移であった.術後2年6カ月経過した現在,再発なく外来通院中である.小腸カルチノイドは偶然発見され,発見時には転移を認めることが多く予後不良と言われている.しかし,肝転移巣に対し外科的切除,肝動注などの直接的な治療を行った症例は予後改善が期待できるとの報告もある.今回われわれは肝転移巣を契機に手術し,偶然に発見した小腸カルチノイドに対し原発巣ならびに肝転移巣を外科的切除しえた1例を経験したので文献的考察を加え報告した.

With the advances in echoendoscopes, the frontier of therapeutic endoscopic ultrasonography (EUS) is expanding. A 50-year-old male presented to us with unrelenting pain following an episode of alcoholic pancreatitis. Imaging studies revealed evidence of pancreatic ductal hypertension with a pseudocyst in the head of the pancreas. Following unsuccessful attempts at drainage of the pancreatic duct (PD) via the minor or major papilla at endoscopic retrograde cholangiopancreatography, he underwent endoscopic ductal drainage with the EUS-assisted rendezvous technique. The PD was punctured under the guidance of EUS. A guidewire was then introduced into the PD and was guided into the duodenal lumen through the minor papilla. The tip of the guidewire was grasped with forceps coming out of a duodenoscope introduced instead of the echoendoscope. A pancreatic stent was inserted over the guidewire across the minor papilla. After the endoscopic pancreatic stenting, the patient achieved symptomatic relief.

We describe a well-differentiated hepatocellular carcinoma (HCC) with alcohol-related liver cirrhosis in a 69-year-old man. Ultrasonography (US) disclosed a 10 mm hypoechoic nodule in segment 4; Sonazoid contrast-enhanced US and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed no defect in either the Kupffer phase or the hepatobiliary phase. Computed tomography during hepatic arteriography (CTHA), however, revealed a hypovascular nodule, but CT during arterial portography showed no perfusion defect. Histological analysis indicated a well-differentiated HCC. Thus, our detection of well-differentiated HCC disclosed by only CTHA attested to the efficiency of this modality, suggesting that it is more sensitive than Gd-EOB-GTPA-enhanced MRI.

We describe a case of serum amyloid A (SAA) and C-reactive protein (CRP) positive nodule detected by immunohistochemical analysis in a 37-year-old woman with alcohol-related cirrhosis. Imaging studies at first admission pointed to hepatocellular carcinoma (HCC), a dysplastic nodule, an inflammatory pseudotumor or focal nodular hyperplasia (FNH). Ultrasonography-guided biopsy in Segment 2 showed minimal atypical changes, except for a slight increase in cell density and micronodular cirrhosis in the non-nodular portion. gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging carried out after a year and a half revealed hypervascularity in the arterial phase and isointensity in the hepatobiliary phase. Three years thereafter, however, the imaging displayed a change from isointensity to a defect in the hepatobiliary phase, and the nodule demonstrated minimal histological atypia. Immunohistochemical staining of the nodule was positive for SAA, CRP, liver fatty acid-binding protein and glutamine synthetase, but negative for β-catenin, heat shock protein 70 and Glypican 3. Organic anion transporter (OATP)8 staining was weaker in the nodule than in the non-nodular portion of the alcohol-related micronodular cirrhosis. The nodule was diagnosed as an SAA and CRP positive nodule, and HCC was ruled out. Despite the change from isointensity to a defect in the hepatobiliary phase, no evidence of HCC was found in the biopsy specimen. The change may be explained more by the weak OATP8 staining compared with that of alcohol-related liver cirrhosis than by malignant transformation into HCC.

Background/Aims: Insulin resistance (IR) has been reported to be an independent predictor of treatment outcome in chronic hepatitis C patients. Methods: We analyzed the relationship between IR and the outcome of pegylated interferon and ribavirin (PEG-IFN/RBV) therapy, taking into account host factors of body mass index and histological index, such as rate of fatty change and fibrosis. Japanese patients (n = 30; 19 men and 11 women; median age 60.0 ± 8.7 years) with chronic hepatitis C-1b with a high viral load were treated with PEG-IFN-α2b/RBV for 48 weeks. Results: Sustained virological response (SVR) was seen in 60% (18/30) and non-SVR in 40% (12/30). HOMA-IR (homeostasis model of assessment-insulin resistance index) at the start and at 24 weeks of treatment showed no statistical difference between SVR and non-SVR. Correlation was observed between HOMA-IR and body mass index (r = 0.45, p = 0.013). Among 20 patients, steatosis and fibrosis were assessed by biopsy. Correlation was observed between HOMA-IR and steatosis (r = 0.57, p = 0.0093), whereas no correlation was observed between HOMA-IR and fibrosis. Conclusion: A larger prospective study is needed to clarify the role of IR in the outcome of PEG-IFN/RBV combination therapy and hepatic fibrosis in Japanese patients.

Although endoscopic ultrasonography (EUS) has the advantage over other imaging methods in that it is possible to obtain high resolution images of the pancreas, it is limited in its ability to characterize pancreatic masses. Contrast-enhanced power Doppler ultrasonography suffers from several limitations such as blooming artifacts, poor spatial resolution, low sensitivity to slow flow and high sensitivity to motion artifacts. Recently, EUS system specific for contrast harmonic imaging has been developed. The use of this EUS system enabled us to observe images of microcirculation and parenchymal perfusion without Doppler-related artifacts in the pancreas. Contrast-enhanced harmonic EUS could diagnose pancreatic carcinomas as hypovascular masses with a high sensitivity (89-96%) and specificity (64-88%). Contrast-enhanced harmonic EUS also discriminates mural nodules from mucous clots in the intraductal papillary mucinous neoplasms.

Endoscopic ultrasonography (EUS) is superior to all other imaging modalities in detecting small pancreatic cancers. However, its ability to characterize hypoechoic pancreatic masses is limited: most carcinomas, neuroendocrine tumors, and inflammatory pseudotumors are simply depicted as hypoechoic masses. Contrast enhancement helps EUS to characterize such hypoechoic masses. Intravenous ultrasound (US) agents increase the signal from the blood and, thus, act as amplifiers and improve visualization of blood flow in small vessels using Doppler US. Contrast-enhanced Doppler EUS can differentiate small pancreatic carcinomas that cannot be detected by other imaging modalities. The development of second-generation US contrast agents and an EUS system with a broad-band transducer enabled the visualization of microvessels and the parenchymal perfusion in the pancreas. This contrast-enhanced harmonic EUS has shown that most pancreatic cancers exhibit hypovascular heterogeneous enhancement with irregular network-like microvessels. Moreover, it can diagnose pancreatic cancers with a high sensitivity (89–92%).

Background: Endoscopic ultrasonography (EUS)-guided choledochoduodenostomy (CDS) is as an alternative to percutaneous transhepatic biliary drainage (PTBD) in patients with biliary obstruction when endoscopic retrograde biliary drainage (ERBD) is unsuccessful. Purpose: We reviewed our experience and technique in patients undergoing EUS-CDS. Patients: Over a 2-year period to December 2008, 15 patients with unsuccessful ERBD underwent EUS-CDS. Methods: EUS-guided needle puncture was performed to access the bile duct from the duodenal bulb. After cholangiography, a guidewire was inserted through the needle and directed to the hepatic hilum. The punctured fistula was then dilated with a biliary dilator and a plastic stent was inserted. Results: The technical success rate of EUS-CDS was 93% (14/15 patients); 1 patient underwent an EUS-guided rendezvous approach because the choledochoduodenal fistula could not be dilated. Decompression of the bile duct was achieved in all patients. Complications included cholangitis in 4 patients, self-limiting local peritonitis in 2 and distal stent migration in 1 patient. The median follow-up time was 125 days and the median duration of stent patency was 99 days. Conclusion: EUS-CDS may be effective for patients following unsuccessful ERBD and offers an attractive alternative to PTBD.

Endoscopic ultrasonography (EUS)-guided celiac plexus neurolysis (EUS-CPN) is safe and effective but not beneficial for some patients with extended abdominal cancer. We compared the effectiveness of standard EUS-CPN and EUS-guided broad plexus neurolysis (EUS-BPN) that extends over the superior mesenteric artery (SMA) using a 25-gauge needle.Consecutive patients referred to our quaternary EUS centers were eligible for inclusion. To evaluate the neurolytic spread, contrast was mixed with the neurolytic agent and post-procedure computed tomography scanning was performed. The regions containing the celiac, superior, and inferior mesenteric arteries were divided on the frontal plane into six areas: upper right and left, middle right and left, and lower right and left. The number of contrast-bearing areas after EUS-CPN and EUS-BPN were related to the degree of pain relief achieved.A total of 67 patients with advanced abdominal cancer were included (34 EUS-CPN and 33 EUS-BPN). The qualitative variables of the two groups did not differ significantly. The EUS-BPN group had more patients with six contrast-bearing areas (42%) than the EUS-CPN group (0%). These patients had significantly better short-term and long-lasting pain relief than patients with less than five contrast-bearing areas. EUS-BPN patients exhibited significantly greater reductions in days 7 and 30 visual analog pain scale scores than EUS-CPN patients.Our preliminary data suggested that EUS-BPN using a 25-gauge needle provides patients with advanced abdominal cancer with better pain relief than standard EUS-CPN, and without incurring serious complications. Moreover, it seems that broad neurolysis over the SMA may provide superior analgesia.

With the advances in echoendoscopes, the frontier of therapeutic endoscopic ultrasonography (EUS) is expanding. A 50-year-old male presented to us with unrelenting pain following an episode of alcoholic pancreatitis. Imaging studies revealed evidence of pancreatic ductal hypertension with a pseudocyst in the head of the pancreas. Following unsuccessful attempts at drainage of the pancreatic duct (PD) via the minor or major papilla at endoscopic retrograde cholangiopancreatography, he underwent endoscopic ductal drainage with the EUS-assisted rendezvous technique. The PD was punctured under the guidance of EUS. A guidewire was then introduced into the PD and was guided into the duodenal lumen through the minor papilla. The tip of the guidewire was grasped with forceps coming out of a duodenoscope introduced instead of the echoendoscope. A pancreatic stent was inserted over the guidewire across the minor papilla. After the endoscopic pancreatic stenting, the patient achieved symptomatic relief.

Background Contrast-enhanced harmonic EUS (CEH-EUS) is a new sonographic technique that uses US contrast agents and depicts intratumoral vessels in real time. Objective To evaluate whether assessment of tumor vascularity by CEH-EUS can predict the preoperative malignancy risk of GI stromal tumors (GISTs). Design Prospective study to observe GIST vascularity. Setting Kinki University School of Medicine. Patients Between June 2007 and September 2009, 76 consecutive patients suspected of having subepithelial lesions underwent CEH-EUS. Intervention CEH-EUS was performed by using a prototype echoendoscope in an extended pure harmonic detection mode. Main Outcome Measurements Resected GIST specimens in 29 patients who underwent surgical resection were divided into high-grade (n = 16) and low-grade (n = 13) malignancy groups based on mitotic activity. The abilities of EUS-guided FNA and CEH-EUS to diagnose the malignant potential were compared. The sensitivities with which contrast-enhanced multidetector CT, power-Doppler EUS, and CEH-EUS detected intratumoral vessels in high-grade malignancy GISTs also were compared. Results CEH-EUS identified irregular vessels and thereby predicted GIST malignancies with a sensitivity, specificity, and accuracy of 100%, 63%, and 83%, respectively. Diagnosis of high-grade malignancy GISTs by EUS-guided FNA had a sensitivity, specificity, and accuracy of 63%, 92%, and 81%, respectively. Contrast-enhanced multidetector CT, power-Doppler EUS, and CEH-EUS detected intratumoral vessels in high-grade malignancy GISTs with sensitivities of 31%, 63%, and 100%, respectively ( P Limitations A single center was involved in this study. Conclusions CEH-EUS successfully visualized intratumoral vessels and may play an important role in predicting the malignancy risk of GISTs.

Endoscopic ultrasonography (EUS) is a highly sensitive diagnostic method for the detection of small pancreatic carcinomas. Recently, there have been some reports describing the utility of contrast-enhanced harmonic EUS (CEH-EUS) which uses sonographic contrast agent for differentiation of a pancreatic mass. This report describes a case of small adenocarcinoma of the pancreas distinct from branch duct intraductal papillary mucinous neoplasm (IPMN) in which investigation by EUS took place every 6 mo and diagnosis was made accurately by additional CEH-EUS during the follow-up of the branch duct IPMN. A 68-year-old female was admitted to our hospital because of a branch duct IPMN in the pancreatic body. She had been followed-up by EUS every 6 mo. However, after 2 years EUS demonstrated a low echoic area distinct from the branch duct IPMN which was vaguely discernible by EUS, and accurate sizing and differential diagnosis were considered difficult on the EUS imaging. CH-EUS with Sonazoid revealed a hypovascular tumor and we suspected small pancreatic carcinoma. The histopathological diagnosis was adenocarcinoma (10 mm) in the pancreatic tail, distinct from the branch duct IPMN of the pancreatic body. EUS and CEH-EUS may play an important role in the correct diagnosis of small pancreatic tumors, including synchronous and metachronous occurrence of IPMN and ductal adenocarcinoma of the pancreas.

Background Microdialysis has been used in vivo to measure dynamic temporal variations in extracellular or interstitial concentrations of non-protein–bound substances that are unstable in the systemic circulation. Objective To evaluate the technical feasibility and possible complications of EUS-guided in vivo microdialysis of the pancreas. Design and Intervention Under the guidance of an echoendoscope inserted into the stomach of each dog, the pancreatic parenchyma was punctured by using a 19-gauge needle. A specially developed microdialysis probe threaded through the lumen of the 19-gauge needle was positioned in the pancreas. The probe was constantly perfused with saline solution at a flow rate of 1.0 μL/minute. Setting Experiments on 8 beagle dogs. Main Outcome Measurements The concentration of 5-fluorouracil (5-FU) in the microdialysate was measured at 10-minute intervals, once before and for 8 times after a single (20 mg/kg) bolus intravenous infusion of 5-FU. Results Following the administration of 5-FU, the concentration of 5-FU in all macrodialysate samples exceeded the cut-off value by more than 100-fold. The 5-FU levels in the microdialysate increased rapidly, peaked by 10 minutes (13.9 μg/mL), and gradually declined thereafter. No local bleeding or accumulation of fluid around the pancreas was observed. Limitation Sampling was unsuccessful in 2 of the 8 dogs because the probe broke while being inserted into the pancreatic parenchyma. Conclusion EUS-guided pancreatic microdialysis is feasible and has multiple potential clinical/therapeutic applications, including monitoring pharmacokinetics focally and detecting novel biomarkers that are unstable or undetectable in the plasma.

Background and Study Aims: The aim of this prospective study was to compare fine-needle aspiration guided by endoscopic ultrasonography (EUS-FNA) using 25-gauge and 22-gauge needles with the EUS-guided 19-gauge Trucut needle biopsy (EUS-TNB) in patients with solid pancreatic mass. Patients and Methods: Twenty-four consecutive patients with pancreatic mass underwent biopsies by both EUS-FNA and EUS-TNB. Three needles were compared with respect to technical success rate, tissue size obtained, overall diagnostic accuracy and accuracy for histological and cytological diagnosis. Results: The 25-gauge EUS-FNA was technically easier and obtained superior overall diagnostic accuracy than the 22-gauge and Trucut needles, especially in lesions of the pancreas head and uncinate process. Overall accuracy for the 25-gauge, 22-gauge and Trucut needle was 91.7%, 79.7% and 54.1%, respectively. Accuracy for cytological diagnosis irrespective the site of lesions with 25-gauge, 22-gauge and Trucut needles was 91.7%, 75.0%, and 45.8%, respectively. For uncinate masses, it was 100%, 33.3%, and 0.0%, respectively. These differences were significant. Among technically successful patients, the accuracy for histological diagnosis using the 25-gauge was significantly inferior (P

Small cell carcinoma (SCC) of the pancreas is a rare entity, with only a few cases reported in the literature. The aim of this study was to evaluate the effectiveness of combination chemotherapy with carboplatin and etoposide (CE) in SCC of the pancreas.We performed a retrospective analysis of four patients diagnosed with SCC among 279 patients with malignant pancreatic tumors treated between 2000 and 2007. All patients were treated with combination chemotherapy using a schedule consisting of intravenous (IV) carboplatin (150 mg/m(2)) on day 1 and IV etoposide (80 mg/m(2)) on days 1, 2, and 3 every 28 days.Pathological diagnosis was confirmed by endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in all patients. Three patients treated with the combination chemotherapy achieved remission, two with a complete response and one with a partial response. The remaining one patient showed no change. One of the two patients with a complete response survived for 56 months following the diagnosis.Combination chemotherapy with CE may be effective for the treatment of SCC of the pancreas; EUS-FNA plays an important role in distinguishing SCC from other pancreatic malignancies, leading to the appropriate treatment being given.

We treated a patient with gastric cancer considered to be unresectable due to peritoneal metastasis, who responded remarkably to treatment with TS-1. The patient was a 62-year-old male. His diagnosis was gastric cancer, for which he underwent surgery on February 22, 2001. Laparotomy disclosed many nodules measuring 2-3 mm in diameter in the abdominal cavity, so rapid pathological tests were conducted during the operation. The test results indicated peritoneal metastasis from gastric cancer. Therefore, simple laparotomy was employed as the best option. On day 13 after surgery, oral administration of TS-1, bid., at a daily dose of 120 mg was commenced. In our outpatient clinic, he was given 3 courses, each comprising 4 weeks' medication and 2 weeks' discontinuation. Subsequently, upper digestive tract endoscopy was performed but only scars in the gastric vestibular area were observed. Biopsy could not detect any malignant findings. Medication was discontinued due to the patient's preference and he died of gastric cancer 10 months after operation.

Ten cases of advanced and metastatic gastric cancer treated by weekly administration of paclitaxel were studied. The patients were 50-72 years of age, including 9 men and 1 woman. In this study, paclitaxel was administered by 1 hour intravenous infusion at a dose of 50-80 mg/m2 every week. Administration was continued for 3 weeks with 1 week rest. One to four cycles were performed at minimum. Paclitaxel was administered in 5 cases as 1st line treatment, 4 cases as 2nd line treatment and 1 case as 3rd line treatment. There were 2 partial responders and no complete responders, and the overall response rate was 20%. The response rate was 100% in liver, 100% in lung, 16% in lymphnodes, and 0% in peritonial dissemination. The clinical symptoms of pain and jaundice abated in one case, the size of the tumor decreased in one case, and a temporary decrease of ascites due to peritonial dissemination was seen in two cases. The level of tumor marker was decreased in 3 out of 10 cases. Side effects included grade 3/4 leukopenia in 10% of patients, and alopecia in 50%, but peripheral neuropathy was not observed. Weekly administration of paclitaxel appears to be well-tolerated and effective against advanced and metastatic gastric cancer.

Su1381 EUS-Guided Gallbladder Drainage As an Alternative Treatment for Malignant Biliary Obstruction After Unsuccessful ERCP: Outcomes of Long Term Follow-Up Masayuki Kitano, Hajime Imai, Ken Kamata, Takamitsu Komaki, Hiroki Sakamoto, Masatoshi Kudo Department of Gastroenterology and Hepatology, Kinki University, Osaka-sayama, Japan Background and Aims: Transpapillary biliary drainage is sometimes difficult due to severe biliary stricture, duodenal stenosis and surgically altered anatomy. EUSguided drainage has been recognized as an alternative method enabling the internal drainage. Recently, EUS-guided gallbladder drainage (EUS-GBD) was reported as a treatment of decompression for acute cholecystitis. We employed the new technique as an alternative treatment for malignant obstructive jaundice and assessed its outcomes of long term follow-up. Patients and Methods: A total of 10 patients underwent EUS-GBD for treatment of acute cholecystitis due to obstruction of cystic duct by a covered metal stent (CMS) (n 5) and obstructive jaundice due to malignant biliary stricture (n 5). In 5 patients with obstructive jaundice, transpapillary drainage had been unsuccessful, and EUS revealed that the cystic duct was not involved by the tumor. A linear echoendoscope was introduced into the stomach or the duodenum. Following visualization of a swollen gallbladder adjacent to the gastric antrum or the duodenal bulb, the echoendoscope was manipulated in order to identify an appropriate puncture route that has no interposing vessels. The gallbladder was punctured with a 19G needle under the enodsonographic guidance. After the gallbladder is irrigated by a large amount of saline ( 500mL) to avoid the peritonitis by leakage of the bile, a 0.025-inch guide wire is introduced until it was coiled within the gallbladder, and then 5.5-9-Fr catheters were serially advanced over the guide wire to dilate the tract. Finally, a 7-Fr. pigtail-type stent was deployed in the gallbladder. The technical success, the functional success, the complications and the stent patency were assessed. Results: The gallbladder was successfully punctured by the needle and irrigated in all patients. The needle was punctured from the stomach and the duodenum in 7 and 3 patients, respectively. However, dilation of the punctured hole was difficult in 2 of 5 patients with acute cholecystitis caused by the CMS due to thickening of the gallbladder wall. Consequently, these 2 patients were followed up after a single aspiration and irrigation. The remaining 8 patients underwent deployment of a stent after successful dilation of the punctured hole. The symptoms were relieved in all patients. Two weeks after the procedure, the bilirubin level was decreased in the 5 patients with obstructive jaundice. No apparent complications such as peritonitis and bleeding occurred in all patients. The median survival time was 134 days (range51-236 days). No additional intervention was needed in 9 patients except a patient treated with a single aspiration of the gallbladder. Conclusion: EUS-guided gallbladder drainage is a possible alternative treatment of decompression in the biliary system when the transpapillary drainage is unsuccessful.