Takaaki Chikugo

Prospective comparative study of the EUS guided 25-gauge FNA needle with the 19-gauge Trucut needle and 22-gauge FNA needle in patients with solid pancreatic masses.

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.

Value of EUS in early detection of pancreatic ductal adenocarcinomas in patients with intraductal papillary mucinous neoplasms.

BACKGROUND AND STUDY AIMS Pancreatic ductal adenocarcinomas (PDAC) sometimes arise in patients with intraductal papillary mucinous neoplasms (IPMNs). This study examined the incidence of PDACs concomitant to or derived from branch duct IPMNs. The usefulness of endoscopic ultrasonography (EUS) relative to other imaging methods for detecting these tumors was also assessed. PATIENTS AND METHODS This retrospective study used data from clinical records and imaging studies that were collected prospectively. During 2001-2009, 167 consecutive patients with IPMNs underwent EUS, ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). The 102 patients whose branch duct IPMNs lacked mural nodules/symptoms and thus did not qualify for resection were followed up by semiannual EUS and annual ultrasonography, CT, and MRI. The sensitivity and specificity with which the four modalities detected IPMN-derived and -concomitant PDACs at the first examination and throughout the study period were evaluated. The rate of PDAC development during follow-up was analyzed by the Kaplan-Meier method. RESULTS A total of 17 IPMN-derived and 11 IPMN-concomitant PDACs were diagnosed at the first examination. Lesions that did not qualify for resection or chemotherapy were followed up for a median of 42 months. Seven IPMN-concomitant PDACs and no IPMN-derived PDACs were detected during follow-up. The 3- and 5-year rates of IPMN-concomitant PDAC development were 4.0% and 8.8%, respectively. At the first examination, EUS was superior to other imaging modalities in terms of IPMN-derived and -concomitant PDAC detection. Throughout the study period, including follow-up, EUS was significantly better at detecting IPMN-concomitant PDACs than the other modalities. CONCLUSIONS IPMN-concomitant PDACs are quite often found at diagnosis and during follow-up. EUS examination of the whole pancreas plays an important role in the management of IPMNs as it allows the early detection of these small invasive carcinomas.

EUS-Guided Broad Plexus Neurolysis Over the Superior Mesenteric Artery Using a 25-Gauge Needle

OBJECTIVES: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.METHODS: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.RESULTS: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.CONCLUSIONS: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.

Therapeutic effects of imidapril on cerebral lesions observed by magnetic resonance imaging in malignant stroke-prone spontaneously hypertensive rats

Objective Magnetic resonance imaging (MRI) was used to investigate the therapeutic effects of imidapril, a newly synthesized angiotensin converting enzyme (ACE) inhibitor, on cerebral stroke lesions. Design Pretreatment with ACE inhibitors is known to prevent stroke in stroke-prone spontaneously hypertensive rats, prolonging their lifespan. Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) were treated with imidapril after the onset of stroke. Methods M-SHRSP with proved stroke were divided into two groups. One group received 40mg/kg per day imidapril and the other group was used as a control. For 4 weeks, neurological symptoms were scored daily, and MRI images were taken and scored once a week. Results In the control group the MRI score for cerebral lesions increased during the experiment, and seven out of eight control rats died within 17 days. In rats treated with imidapril the major finding was that imidapril rapidly ameliorated the damage to the blood-brain barrier and resolved brain oedema within 1 week. At the same time the neurological symptoms observed after stroke disappeared. Furthermore, none of the rats treated with imidapril showed recurrence of stroke, and their survival rate was improved. Conclusion These results suggest that imidapril has therapeutic effects on stroke lesions, as well as prophylactic effects on the recurrence of stroke.

Contrast-enhanced harmonic endoscopic ultrasonography for differential diagnosis of pancreatic cysts

BACKGROUND AND STUDY AIM Comparison of fundamental B-mode endoscopic ultrasonography (FB-EUS) and contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) in the differential diagnosis of pancreatic cysts according to presence of mural nodules. PATIENTS AND METHODS Between April 2007 and April 2012, FB-EUS and CH-EUS data were prospectively collected from 581 consecutive patients with pancreatic cysts, and were retrospectively analyzed from 70 with subsequent cyst resection. Presence and height of mural nodules as detected on FB-EUS and CH-EUS were evaluated, and thence accuracies of both methods for diagnosing mucinous versus nonmucinous and malignant versus benign cysts. RESULTS On pathological examination 48 cysts were mucinous and 22 were nonmucinous; 30 cysts were malignant (high grade dysplasia or invasive carcinoma) and 40 were benign. If presence of a mural nodule was considered to indicate a mucinous cyst, FB-EUS and CH-EUS accuracies did not differ significantly (respectively: sensitivity 85 % vs. 79 %; specificity 46 % vs. 96 %; accuracy 73 % vs. 84 %, P = 0.057). If presence of mural nodule was considered to indicate malignancy, CH-EUS was significantly more accurate than FB-EUS (respectively: sensitivity 97 % vs. 97 %; specificity 75 % vs. 40 %; accuracy 84 % vs. 64 %, P = 0.0001). For diagnosing malignancy by evaluating mural nodule height, the area under the receiver operating characteristic (AUROC) was 0.84 and 0.93 for FB-EUS and CH-EUS, respectively (P = 0.028). Presence of a mural nodule of height ≥ 4 mm on CH-EUS was a sign of malignancy (false-positive fraction 0.2; true-positive fraction 0.93; odds ratio 56.0). CONCLUSIONS CH-EUS is more accurate than FB-EUS for diagnosing malignant pancreatic cysts.

Carcinoma ex pleomorphic adenoma of the parotid gland

Background Carcinoma ex pleomorphic adenoma (CXPA) is a rare aggressive epithelial malignancy arising from a primary or recurrent benign mixed tumor. Only a few case reports describing the radiologic features of CXPA have been published. Purpose To describe and characterize the magnetic resonance (MR) imaging findings of CXPA in the parotid gland and correlate them with pathologic findings. Material and Methods The MR images of surgically proven CXPA in the parotid gland of five men and five women ranging in age from 28 to 75 years (mean 52 years) were retrospectively reviewed. All MR images were evaluated with emphasis on the size, margin characteristics, extraparotid infiltration, the presence of an encapsulated component, and signal intensity on T2-weighted or short-inversion-time inversion recovery (STIR) images. Results The average maximal diameter was 4.3 cm. All 10 tumors had ill-defined boundaries, and seven tumors showed extraparotid infiltration, reflecting invasive growth of the malignant component identified on histological examination. Eight tumors had a round encapsulated component and seven of those signal intensities were a mixture of hypo- and hyperintensity on T2-weighted or STIR images. Histological correlation of these components revealed fibrously encapsulated tumors containing hyalinization and myxoid tissue, suggesting degenerated pleomorphic adenoma. Invasive malignant components had non-specific and various signal intensities. Conclusion An invasive parotid mass co-existing with a round encapsulated component is suggestive of carcinoma ex pleomorphic adenoma.

Plasma Concentrations of Angiogenesis-related Molecules in Patients with Pancreatic Cancer

BACKGROUND Anti-angiogenic agents are now being clinically evaluated for the treatment of pancreatic cancer and a detailed investigation of the angiogenic profile of pancreatic cancer is needed. The aim of this study was to evaluate the plasma concentrations of angiogenesis-related molecules in patients with pancreatic cancer, compared with those with other diseases. METHODS Plasma samples obtained from 45 patients with pancreatic cancer were analyzed and compared with those from 9 patients with pancreatitis, 16 patients with benign hepatobiliary diseases and 58 patients with colorectal cancers. The plasma levels of angiogenesis-related molecules including angiopoietin-2, follistatin, granulocyte-colony stimulating factor, hepatocyte growth factor, interleukin-8, leptin, platelet-derived growth factor beta polypeptide, platelet endothelial cell adhesion molecule-1 and vascular endothelial growth factor were determined using an antibody suspension bead arrays system. RESULTS The plasma levels of all the angiogenesis-related molecules were not increased in patients with pancreatic cancer, compared with those with pancreatitis and benign hepatobiliary diseases, whereas the levels of those with colorectal cancer were markedly increased. The plasma interleukin-8 concentration was significantly elevated in patients with distant metastases and was associated with a poor treatment outcome of chemotherapy in patients with pancreatic cancer. CONCLUSIONS The plasma levels of angiogenesis-related molecules were not elevated in patients with pancreatic cancer, compared with those with benign diseases or colorectal cancer. The plasma interleukin-8 level may be a novel biomarker for the response to chemotherapy in patients with pancreatic cancer and warrants further prospective study.

Removal of diminutive colorectal polyps: A prospective randomized clinical trial between cold snare polypectomy and hot forceps biopsy

AIM To compare the efficacy and safety of cold snare polypectomy (CSP) and hot forceps biopsy (HFB) for diminutive colorectal polyps. METHODS This prospective, randomized single-center clinical trial included consecutive patients ≥ 20 years of age with diminutive colorectal polyps 3-5 mm from December 2014 to October 2015. The primary outcome measures were en-bloc resection (endoscopic evaluation) and complete resection rates (pathological evaluation). The secondary outcome measures were the immediate bleeding or immediate perforation rate after polypectomy, delayed bleeding or delayed perforation rate after polypectomy, use of clipping for bleeding or perforation, and polyp retrieval rate. Prophylactic clipping after polyp removal wasn’t routinely performed. RESULTS Two hundred eight patients were randomized into the CSP (102), HFB (106) and 283 polyps were evaluated (CSP: 148, HFB: 135). The en-bloc resection rate was significantly higher with CSP than with HFB [99.3% (147/148) vs 80.0% (108/135), P < 0.0001]. The complete resection rate was significantly higher with CSP than with HFB [80.4% (119/148) vs 47.4% (64/135), P < 0.0001]. The immediate bleeding rate was similar between the groups [8.6% (13/148) vs 8.1% (11/135), P = 1.000], and endoscopic hemostasis with hemoclips was successful in all cases. No cases of perforation or delayed bleeding occurred. The rate of severe tissue injury to the pathological specimen was higher HFB than CSP [52.6% (71/135) vs 1.3% (2/148), P < 0.0001]. Polyp retrieval failure was encountered CSP (7), HFB (2). CONCLUSION CSP is more effective than HFB for resecting diminutive polyps. Further long-term follow-up study is required.

MULTIPLE NONFUNCTIONAL PANCREATIC ISLET CELL TUMOR IN MULTIPLE ENDOCRINE NEOPLASIA TYPE I

A case of multiple nonfunctional pancreatic islet cell tumor in multiple endocrine neoplasia type I (MEN I) is reported. The patient was a 41‐year‐old woman who had a past history of thyroid cancer (papillary carcinoma) and hyperparathyroidism due to parathyroid adenoma. Later, a nonfunctional pituitary tumor and Ave nonfunctional pancreatic tumors were found simultaneously and the patient was finally diagnosed as having MEN I. Following surgical enucleation, the pancreatic tumors were histopathologlcally diagnosed as benign islet cell tumors. One of them (tumor 3) exhibited a solid nodular pattern while the others showed gyriform patterns. They were divided histochemlcally and immunohistochemically into three types: two (tumors 1 and 2) produced a single hormone (glucagon), one (tumor 3) produced five (Insulin, glucagon, somatostatin, gastrin and pancreatic polypeptide) and the remaining two (tumors 4 and 5) produced two (glucagon and pancreatic polypeptide). Electron microscopically, three types of endosecretory granules were found in the tumor cells of tumor 3 but only one type was found in tumor 4. However, in the tumor 4 extract, glucagon, pancreatic polypeptide, C‐peptlde, somatostatin, vasoactive intestinal peptide and growth hormone releasing factor were detected by radioimmunoassay. These findings suggest that these pancreatic tumors were both multicellular and multihormonal.

Increased Ectodomain Shedding of Cell Adhesion Molecule 1 from Pancreatic Islets in Type 2 Diabetic Pancreata: Correlation with Hemoglobin A1c Levels

Pulmonary emphysema and type 2 diabetes mellitus (T2DM), both caused by lifestyle factors, frequently concur. Respectively, the diseases affect lung alveolar and pancreatic islet cells, which express cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member. Protease-mediated ectodomain shedding of full-length CADM1 produces C-terminal fragments (CTFs) with proapoptotic activity. In emphysematous lungs, the CADM1 shedding rate and thus the level of CTFs in alveolar cells increase. In this study, CADM1 expression in islet cells was examined by western blotting. Protein was extracted from formalin-fixed, paraffin-embedded sections of pancreata isolated from patients with T2DM (n = 12) or from patients without pancreatic disease (n = 8) at autopsy. After adjusting for the number of islet cells present in the adjacent section, we found that full-length CADM1 decreased in T2DM islets, while ectodomain shedding increased. Hemoglobin A1c levels, measured when patients were alive, correlated inversely with full-length CADM1 levels (P = 0.041) and positively with ectodomain shedding rates (P = 0.001). In immunofluorescence images of T2DM islet cells, CADM1 was detected in the cytoplasm, but not on the cell membrane. Consistently, when MIN6-m9 mouse beta cells were treated with phorbol ester and trypsin to induce shedding, CADM1 immunostaining was diffuse in the cytoplasm. When a form of CTFs was exogenously expressed in MIN6-m9 cells, it localized diffusely in the cytoplasm and increased the number of apoptotic cells. These results suggest that increased CADM1 ectodomain shedding contributes to blood glucose dysregulation in T2DM by decreasing full-length CADM1 and producing CTFs that accumulate in the cytoplasm and promote apoptosis of beta cells. Thus, this study has identified a molecular alteration shared by pulmonary emphysema and T2DM.