Masahiro Itonaga

Usefulness of contrast-enhanced endoscopic sonography for discriminating mural nodules from mucous clots in intraductal papillary mucinous neoplasms: a single-center prospective study.

The aim of this study was to evaluate the ability of contrast‐enhanced endoscopic sonography for discrimination of mural nodules from mucous clots in intraductal papillary mucinous neoplasms of the pancreas.

Contrast-enhanced endoscopic ultrasonography can predict a higher malignant potential of gastrointestinal stromal tumors by visualizing large newly formed vessels

The aim of this study was to elucidate the histologic and clinical implications of detection of intratumoral vessels on contrast‐enhanced endoscopic ultrasonography (CE‐EUS) in gastrointestinal stromal tumors (GISTs).

Novel Methodology for Rapid Detection of KRAS Mutation Using PNA-LNA Mediated Loop-Mediated Isothermal Amplification.

Detecting point mutation of human cancer cells quickly and accurately is gaining in importance for pathological diagnosis and choice of therapeutic approach. In the present study, we present novel methodology, peptide nucleic acid—locked nucleic acid mediated loop-mediated isothermal amplification (PNA-LNA mediated LAMP), for rapid detection of KRAS mutation using advantages of both artificial DNA and LAMP. PNA-LNA mediated LAMP reactions occurred under isothermal temperature conditions of with 4 primary primers set for the target regions on the KRAS gene, clamping PNA probe that was complimentary to the wild type sequence and LNA primers complementary to the mutated sequences. PNA-LNA mediated LAMP was applied for cDNA from 4 kinds of pancreatic carcinoma cell lines with or without KRAS point mutation. The amplified DNA products were verified by naked-eye as well as a real-time PCR equipment. By PNA-LNA mediated LAMP, amplification of wild type KRAS DNA was blocked by clamping PNA probe, whereas, mutant type KRAS DNA was significantly amplified within 50 min. Mutant alleles could be detected in samples which diluted until 0.1% of mutant-to-wild type ratio. On the other hand, mutant alleles could be reproducibly with a mutant-to-wild type ratio of 30% by direct sequencing and of 1% by PNA-clamping PCR. The limit of detection (LOD) of PNA-LNA mediated LAMP was much lower than the other conventional methods. Competition of LNA clamping primers complementary to two different subtypes (G12D and G12V) of mutant KRAS gene indicated different amplification time depend on subtypes of mutant cDNA. PNA-LNA mediated LAMP is a simple, rapid, specific and sensitive methodology for the detection of KRAS mutation.

Tumor vessel depiction with contrast-enhanced endoscopic ultrasonography predicts efficacy of chemotherapy in pancreatic cancer.

Objectives Contrast-enhanced endoscopic ultrasonography (CE-EUS) is a new imaging modality for pancreatic lesions. The aim of this study was to evaluate if CE-EUS is useful for predicting treatment efficacy before pancreatic cancer chemotherapy by assessing intratumoral vessel flow. Methods Thirty-nine patients with unresectable advanced pancreatic cancer underwent CE-EUS before chemotherapy. The patients were divided into 2 groups according to the intratumoral vessel flow observed with CE-EUS: vessel sign–positive and vessel sign–negative groups. Patient prognosis was investigated according to presence or absence of the vessel sign. Results Two patients were excluded due to poor visualization of CE-EUS images; therefore, 37 patients were analyzed. Contrast-enhanced EUS revealed positive vessel sign in 20 patients, whereas it revealed negative vessel sign in 17 patients. Both progression-free survival and overall survival were significantly longer in the positive- versus negative vessel sign groups (P = 0.037 and P = 0.027, respectively). Multivariate analysis demonstrated that the positive vessel sign was an independent factor associated with longer overall survival (hazard ratio, 0.22; 95% confidence interval, 0.08–0.53). Conclusions Evaluation of intratumoral vessel flow by CE-EUS could be useful for predicting efficacy of chemotherapy in patients with pancreatic cancer. Contrast-enhanced EUS could be used before chemotherapy for inoperable pancreatic cancer.

Contrast-Enhanced Endoscopic Ultrasonography for Pancreatic Tumors

Objectives. To investigate the usefulness of contrast-enhanced endoscopic ultrasonography (CE-EUS) for histological differentiation of pancreatic tumors. Methods. CE-EUS was performed for consecutive patients having a pancreatic solid lesion, and tumors were classified into three vascular patterns (hypervascular, isovascular, and hypovascular) at two time phases (early-phase and late-phase). Correlation between vascular patterns and histopathology of resected pancreatic cancer (PC) tissues was ascertained. Results. The final diagnoses of 147 examined tumors were PC (n = 109), inflammatory mass (n = 11), autoimmune pancreatitis (n = 9), neuroendocrine tumor (n = 8), and others (n = 10). In late-phase images, 104 of 109 PCs had the hypovascular pattern, for a diagnostic sensitivity and specificity of 94% and 71%, respectively. Of 28 resected PCs, 10 had isovascular, and 18 hypovascular, patterns on the early-phase image. Early-phase isovascular PCs were more likely to be differentiated than were early-phase hypovascular PCs (6 well and 4 moderately differentiated versus 3 well, 14 moderately, and 1 poorly differentiated, P = 0.028). Immunostaining revealed that hypovascular areas of early-phase images reflected heterogeneous tumor cells with fibrous tissue, necrosis, and few vessels. Conclusion. CE-EUS could be useful for distinguishing PC from other solid pancreatic lesions and for histological differentiation of PCs.

Phlegmonous gastritis caused by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA)

Phlegmonous gastritis (PG) is a rare, often fatal, condition characterized by suppurative bacterial infection of the stomach. Mucosal damage of the stomach, alcoholism and an immunocompromised state are predisposing factors. Phlegmonous gastritis rarely develops after therapeutic endoscopy and only a few instances have been reported. We describe a patient with PG that arose as a complication after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). A 70-year-old woman with a diagnosis of pancreatic tumor attended our hospital. A 50-mm, low echoic lesion at the pancreatic body was identified by EUS and EUS-FNA proceeded through the stomach using a 19-gauge needle (Echo Tip®Ultra;Wilson-Cook,Winston Salem, NC, USA). She was discharged on the following day. She returned to our hospital 1 week later due to persistent upper abdominal pain and low-grade fever. Her vital signs were: blood pressure, 105/ 66 mmHg; regular pulse, 96 b.p.m. and temperature of 38°C. The patient’s abdomen was soft, flat, and slightly distended with mild tenderness in the upper area. The laboratory findings were as follows: obvious inflammation with white blood cells (WBC) 13 500/mL and C-reactive protein (CRP) 28 mg/ dL. Multi-detector row computed tomography (MDCT) revealed diffuse thickening of the gastric wall and air trapped within it (Fig. 1). Upper gastrointestinal endoscopy revealed diffuse erythema, edema and erosions (Fig. 2). EUS also showed diffuse gastric wall thickening, predominantly in the submucosa (Fig. 3). The culture of several biopsy specimens from the mucosal surface revealed a-Streptococcus and PG caused by EUS-FNA was clinically diagnosed. The patient recovered after antibiotic therapy with peperacillin/ tazobactam and she was discharged on hospital day 15. EUS-FNA is a safe procedure with a complication rate of approximately 1% that does not normally require antibiotic prophylaxis. However, the risk of PG must be considered for immunocompromised patients with advanced cancer and preventative antibiotics may be necessary.

A case of chronic pancreatitis in which endoscopic ultrasonography was effective in the diagnosis of a pseudoaneurysm

Endoscopic ultrasonography (EUS) was performed on a patient being treated for chronic pancreatitis because a submucosal tumor was observed in the stomach during gastrointestinal endoscopy. As internal pulsatile blood flow on Doppler was present, the diagnosis of an aneurysm was made. The pseudoaneurysm of the left gastric artery was embolized with histoacryl and lipiodol and the splenic artery was embolized with coils at the location of the pseudoaneurysm to prevent hemorrhage. Follow up EUS confirmed the cessation of blood flow from the pseudoaneurysm. Clinicians encountering a gastric submucosal tumor-like protrusion in a patient with chronic pancreatitis should use EUS to investigate the possibility of a pseudoaneurysm, which must be treated as quickly as possible once identified.

CURRENT STATUS OF ENDOSCOPIC MANAGEMENT FOR NONVARICEAL UPPER GASTROINTESTINAL BLEEDING

Endoscopic hemostasis is widely performed for nonvariceal upper gastrointestinal (UGI) bleeding. As the aged Japanese population rapidly increases, the number of patients experiencing complications increases. The aim of this study was to evaluate the recent results of endoscopic hemostasis for nonvariceal UGI bleeding. A retrospective analysis of patients who underwent endoscopic procedures for nonvariceal UGI bleeding was performed. We performed 223 endoscopic procedures on 217 patients between January 1995 and July 2000, and 238 endoscopic procedures on 236 patients between January 2006 and September 2009 at the Kyoto Second Red Cross Hospital. We divided the patients into the 1995–2000 group and the 2006–2009 group. Patient characteristics, hemostasis methods chosen, rates of temporary hemostasis and rebleeding, and mortality were analyzed. There were many serious and actively bleeding cases in the 2006–2009 group (P < 0.001). The endoclip method and intravenous proton pump inhibitor were mainly used in the 2006–2009 group compared with the drug‐injection method and intravenous H2 receptor antagonist in the 1995–2000 group (P < 0.001). Through these treatments, the two groups were able to obtain similar treatment outcomes. Through the progress of endoscopic management we obtained similar satisfactory results in the 2006–2009 group, which had multiple complicated cases, compared to the 1995–2000 group.

Real-time contrast-enhanced endoscopic ultrasonography-guided fine-needle aspiration (with video).

The use of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has rapidly increased since first being reported by Vilmann et al. in 1992, and diagnostic sensitivity of 68–94.7%, specificity of 82–100%, and accuracy rates of 83–95% have been reported. However, diagnostic difficulty is sometimes encountered. To delineate the margin of a small unclear tumor and identify areas of necrosis within the tumor, contrast-enhanced ultrasonography can provide useful information for EUS-FNA. Combining contrastenhanced endoscopic ultrasonography with EUS-FNA can be an effective diagnostic tool. Real-time contrast-enhanced EUS-FNA was carried out using an ultrasound endoscope (GF-UCT260; Olympus, Tokyo, Japan) and an ultrasound system (Prosound α10; Aloka, Tokyo, Japan). The ultrasound contrast agent Sonazoid® (Daiichi Sankyo Co., Ltd., Tokyo, Japan) was injected i.v. A 22-gauge needle was used and contrast imaging was done during tumor puncture. Case 1. Contrast computed tomography (CT) in an 80-year-old man showed a 3-cm mass lesion with heterogeneous enhancement in the pancreatic head. EUS-FNA was carried out during contrast imaging. Tissues were obtained from an area without enhancement and an area with enhancement (Video S1). Tissue at the site of necrosis in the no-enhancement area and tissue from tumor cells in the enhancement area were obtained. Histological diagnosis was acinar cell carcinoma (Fig. 1). Case 2. Contrast CT in a 52-year-old man during chemotherapy for lung cancer showed a 10-mm, low-density lesion in the pancreatic tail (Fig. 2). As the margin of the tumor was not clear in fundamental mode, EUS-FNA was carried out during contrast imaging (Video S2). Histological diagnosis was pleomorphic carcinoma with metastases from lung cancer. The advantages of real-time contrast-enhanced EUS-FNA are: (i) identifying areas of necrosis within tumors, enabling biopsy puncture, avoiding this area; and (ii) delineating small tumors in which the border with surrounding pancreatic parenchyma is indistinct, enabling biopsy puncture. This procedure is an effective diagnostic tool.

Rapid On-Site Evaluation by Endosonographers during Endoscopic Ultrasonography-Guided Fine-Needle Aspiration for Diagnosis of Gastrointestinal Stromal Tumors

Background/Aims Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been used to diagnose gastrointestinal submucosal tumors (SMTs). Although rapid on-site evaluation (ROSE) has been reported to improve the diagnostic accuracy of EUS-FNA for pancreatic lesions, on-site cytopathologists are not routinely available. Given this background, the usefulness of ROSE by endosonographers themselves for pancreatic tumors has also been reported. However, ROSE by endosonographers for diagnosis of SMT has not been reported. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA with ROSE by endosonographers for SMT, focusing on diagnosis of gastrointestinal stromal tumor (GIST), compared with that of EUS-FNA alone. Methods Twenty-two consecutive patients who underwent EUS-FNA with ROSE by endosonographers for SMT followed by surgical resection were identified. Ten historical control subjects who underwent EUS-FNA without ROSE were used for comparison. Results The overall diagnostic accuracy for SMT was significantly higher in cases with than without ROSE (100% vs. 80%, p=0.03). The number of needle passes by FNA with ROSE by endosonographers tended to be fewer, although accuracy was increased (3.3±1.3 vs. 5.9±3.8, p=0.06). Conclusions ROSE by endosonographers during EUS-FNA for SMT is useful for definitive diagnosis, particularly for GIST.