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1.  Magnifying Endoscopy with Narrow Band Imaging to Determine the Extent of Resection in Transoral Robotic Surgery of Oropharyngeal Cancer 
Case Reports in Otolaryngology  2014;2014:604737.
Transoral robotic surgery (TORS) is a less invasive treatment that is becoming popular all over the world. One of the most important factors for achieving success in TORS is the ability to determine the extent of resection during the procedure as the extent of resection in the laryngopharynx not only affects oncological outcomes but also directly affects swallowing and voice functions. Magnifying endoscopy with narrow band imaging (ME-NBI) is an innovative optical technology that provides high-resolution images and is useful in detecting early superficial pharyngeal cancers, which are difficult to detect by standard endoscopy. A 55-year-old male with superficial oropharyngeal cancer has been successfully treated by combining MB-NBI with TORS and MB-NBI was useful in determining the extent of resection. ME-NBI with TORS will make it possible to achieve a higher ratio of minimally invasive treatment in pharyngeal cancer.
doi:10.1155/2014/604737
PMCID: PMC4276113  PMID: 25574412
2.  Amenorrhea as a rare drug-related adverse event associated with everolimus for pancreatic neuroendocrine tumors 
World Journal of Gastroenterology : WJG  2014;20(42):15920-15924.
The patient was an asymptomatic 43-year-old woman. Abdominal ultrasonography and enhanced computed tomography showed a tumor lesion accompanied by multiple cystic changes in the liver and the pancreatic tail. Endoscopic ultrasound-fine needle aspiration was performed on the pancreatic tumor lesion and revealed pancreatic neuroendocrine tumor (PNET). As it was unresectable due to multiple liver metastases, the decision was made to initiate treatment with everolimus and transcatheter arterial chemoembolization. The patient ceased menstruating after the start of everolimus administration. When the administration was discontinued due to interstitial lung disease, menstruation resumed, but then again stopped with everolimus resumption. An association between everolimus and amenorrhea was highly suspected. Amenorrhea occurred as a rare adverse event of everolimus. As the younger women might be included in PNETs patients, we should put this adverse event into consideration.
doi:10.3748/wjg.v20.i42.15920
PMCID: PMC4229560  PMID: 25400479
Amenorrhea; Everolimus; Neuroendocrine tumor; Pancreas; Adverse event
3.  Association Mapping and Validation of QTLs for Flour Yield in the Soft Winter Wheat Variety Kitahonami 
PLoS ONE  2014;9(10):e111337.
The winter wheat variety Kitahonami shows a superior flour yield in comparison to other Japanese soft wheat varieties. To map the quantitative trait loci (QTL) associated with this trait, association mapping was performed using a panel of lines from Kitahonami’s pedigree, along with leading Japanese varieties and advanced breeding lines. Using a mixed linear model corrected for kernel types and familial relatedness, 62 marker-trait associations for flour yield were identified and classified into 21 QTLs. In eighteen of these, Kitahonami alleles showed positive effects. Pedigree analysis demonstrated that a continuous pyramiding of QTLs had occurred throughout the breeding history of Kitahonami. Linkage analyses using three sets of doubled haploid populations from crosses in which Kitahonami was used as a parent were performed, leading to the validation of five of the eight QTLs tested. Among these, QTLs on chromosomes 3B and 7A showed highly significant and consistent effects across the three populations. This study shows that pedigree-based association mapping using breeding materials can be a useful method for QTL identification at the early stages of breeding programs.
doi:10.1371/journal.pone.0111337
PMCID: PMC4215981  PMID: 25360619
4.  Accessory Pancreatic Duct-Portal Vein Fistula: A Rare Complication of Chronic Pancreatitis during Endoscopic Retrograde Cholangiopancreatography 
Case Reports in Gastroenterology  2014;8(2):291-296.
Pancreatitis, hemorrhage and perforation are the most frequent complications associated with endoscopic retrograde cholangiopancreatography (ERCP). We report a rare case of accessory pancreatic duct-portal vein fistula, which occurred during ERCP in a patient with chronic pancreatitis. To our knowledge, this is the first report of accessory pancreatic duct-portal vein fistula created during ERCP by the use of a guide wire.
doi:10.1159/000368303
PMCID: PMC4241643  PMID: 25473386
Accessory pancreatic duct-portal vein fistula; Chronic pancreatitis; Endoscopic retrograde cholangiopancreatography
5.  Clinicopathological features and EGFR gene mutation status in elderly patients with resected non–small-cell lung cancer 
BMC Cancer  2014;14(1):610.
Background
The rapid aging of the population in Japan has been accompanied by an increased rate of surgery for lung cancer among elderly patients. It is thus an urgent priority to map out a treatment strategy for elderly patients with primary lung cancer. Although surgical resection remains standard treatment for early stage non–small-cell lung cancer (NSCLC), it is now essential to confirm the status of epidermal growth factor receptor (EGFR) gene mutations when planning treatment strategies. Furthermore, several studies have reported that EGFR mutations are an independent prognostic marker in NSCLC. However, the relations between age group and the molecular and pathological characteristics of NSCLC remain unclear. We studied the status of EGFR mutations in elderly patients with NSCLC and examined the relations of EGFR mutations to clinicopathological factors and outcomes according to age group.
Methods
A total of 388 consecutive patients with NSCLC who underwent complete tumor resection in our hospital from 2006 through 2008 were studied retrospectively. Formalin-fixed, paraffin-embedded tissue sections were used to isolate DNA from carcinoma lesions. Mutational analyses of EGFR gene exons 19, 20, and 21 and KRAS gene exons 12 and 13 were performed by loop-hybrid mobility shift assay, a highly sensitive polymerase chain reaction-based method.
Results
EGFR mutations were detected in 185 (47.7%) and KRAS mutations were detected in 33 (8.5%) of the 388 patients. EGFR mutations were found in a significantly higher proportion of patients younger than 80 years (younger group; 178/359, 49.6%) than in patients 80 years or older (older group; 7/29, 24.1%) (P = 0.008). In contrast, KRAS mutations were more common in the older group (6/29, 20.7%) than in the younger group (27/359, 7.5%) (P = 0.014). The older group showed a trend toward a higher rate of 5-year overall survival among elderly patients with EGFR mutations (100%) than among those with wild-type EGFR (66.2%), but the difference was not significant.
Conclusions
Our results suggest that the EGFR status of patients with NSCLC differs between patients 80 years or older and those younger than 80 years. EGFR mutation status might be a prognostic marker in elderly patients with completely resected NSCLC.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2407-14-610) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2407-14-610
PMCID: PMC4161910  PMID: 25152277
6.  An Intraductal Papillary Neoplasm of the Bile Duct at the Duodenal Papilla 
Case Reports in Oncology  2014;7(2):417-421.
In recent years, the disease concept of intraductal papillary neoplasm of the bile duct (IPNB) has been attracting attention as a biliary lesion that is morphologically similar to intraductal papillary mucinous neoplasm (IPMN), which is considered to be a counterpart of IPMN. However, there are few reports on IPNB, and a consensus regarding the features of this disease is thus lacking. We experienced an extremely rare case of IPNB occurring in the bile duct at the duodenal papilla, which is a tumor presentation that has not previously been reported. Herein, we report this interesting case and discuss the possible association between IPMN and IPNB.
doi:10.1159/000364999
PMCID: PMC4130820  PMID: 25126070
Intraductal papillary neoplasm of the bile duct; Duodenal papilla; Intraductal papillary mucinous neoplasm; Intraductal ultrasound; Peroral cholangioscopy
7.  Severe Pulmonary Suppuration with Infection-Induced Systemic Inflammatory Response Syndrome following Tongue Cancer Surgery in a Patient Undergoing Tocilizumab Therapy for Rheumatoid Arthritis 
Case Reports in Dentistry  2014;2014:649086.
A 65-year-old woman with rheumatoid arthritis treated by tocilizumab (TCZ) presented with tongue squamous cell carcinoma. While surgery was performed without any complications the aspiration pneumonia rapidly worsened by postoperative day 2 and severe pulmonary suppuration in the right lung field with infection-induced systemic inflammatory response syndrome (SIRS) was diagnosed. Antibiotic and respirator treatment improved her condition. The anti-inflammatory effect of TCZ may mask the symptoms and signs of severe infection with SIRS.
doi:10.1155/2014/649086
PMCID: PMC4020557  PMID: 24872899
8.  Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus 
Background
The effects of switching from prandial premixed insulin therapy (PPT) injected three times a day to basal plus two times bolus insulin therapy (B2B) on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus.
Methods
The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner) in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was administered at the start and end of the study.
Results
The glycated hemoglobin (HbA1c) level (8.3%±1.8% to 8.2%±1.1%) and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33%) subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤8.0% (−0.9±2.0 versus 0.3±0.6, respectively, P=0.02). The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7±3.6 versus −0.8±3.5, P=0.04).
Conclusion
B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT.
doi:10.2147/DDDT.S62709
PMCID: PMC4003145  PMID: 24790413
type 2 diabetes mellitus; insulin therapy; basal plus two times bolus insulin therapy; prandial premixed insulin therapy; Diabetes Treatment Satisfaction Questionnaire
9.  Significance of AT1 Receptor Independent Activation of Mineralocorticoid Receptor in Murine Diabetic Cardiomyopathy 
PLoS ONE  2014;9(3):e93145.
Background
Diabetes mellitus (DM) has deleterious influence on cardiac performance independent of coronary artery disease and hypertension. The objective of the present study was to investigate the role of the renin-angiotensin-aldosterone system, especially angiotensin II type 1a receptor (AT1aR) and mineralocorticoid receptor (MR) signaling, in left ventricular (LV) dysfunction induced by diabetes mellitus (DM).
Methods and Results
DM was induced by intraperitoneal injection of streptozotocin (200 mg/kg BW) in wild-type (WT) or AT1aR knockout (KO) male mice, and they were bred during 6 or 12 weeks. Some KO mice were administered the MR antagonist eplerenone (100 mg/kg body weight). At 6 weeks, LV diastolic function was impaired in WT-DM, but preserved in KO-DM. At that time point MR mRNA expression was upregulated, NADPH oxidase subunit (p47phox) and glutathione peroxidase (GPx1) mRNA expression were upregulated, the staining intensities of LV tissue for 4-hydroxy-2-nonenal was stronger in immunohistochemistry, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive cells was increased, Bcl-2 protein expression was significantly downregulated, and the expression of SERCA2a and phosphorylated phospholamban was depressed in WT-DM, while these changes were not seen in KO-DM. At 12 weeks, however, these changes were also noted in KO-DM. Eplerenone arrested those changes. The plasma aldosterone concentration was elevated in WT-DM but not in KO-DM at 6 weeks. It showed 3.7-fold elevation at 12 weeks even in KO-DM, which suggests “aldosterone breakthrough” phenomenon. However, the aldosterone content in LV tissue was unchanged in KO-DM.
Conclusions
DM induced diastolic dysfunction was observed even in KO at 12 weeks, which was ameliorated by minelarocorticoid receptor antagonist, eplerenone. AT1-independent MR activation in the LV might be responsible for the pathogenesis of diabetic cardiomyopathy.
doi:10.1371/journal.pone.0093145
PMCID: PMC3963989  PMID: 24664319
10.  Risk factors for proximal migration of biliary tube stents 
AIM: To analyze the risk factors for biliary stent migration in patients with benign and malignant strictures.
METHODS: Endoscopic stent placement was performed in 396 patients with bile duct stenosis, at our institution, between June 2003 and March 2009. The indications for bile duct stent implantation included common bile duct stone in 190 patients, malignant lesions in 112, chronic pancreatitis in 62, autoimmune pancreatitis in 14, trauma in eight, surgical complications in six, and primary sclerosing cholangitis (PSC) in four. We retrospectively examined the frequency of stent migration, and analyzed the patient factors (disease, whether endoscopic sphincterotomy was performed, location of bile duct stenosis and diameter of the bile duct) and stent characteristics (duration of stent placement, stent type, diameter and length). Moreover, we investigated retrieval methods for migrated stents and their associated success rates.
RESULTS: The frequency of tube stent migration in the total patient population was 3.5%. The cases in which tube stent migration occurred included those with common bile duct stones (3/190; 1.6%), malignant lesions (2/112; 1.8%), chronic pancreatitis (4/62; 6.5%), autoimmune pancreatitis (2/14; 14.3%), trauma (1/8; 12.5%), surgical complications (2/6; 33.3%), and PSC (0/4; 0%). The potential risk factors for migration included bile duct stenosis secondary to benign disease such as chronic pancreatitis and autoimmune pancreatitis (P = 0.030); stenosis of the lower bile duct (P = 0.031); bile duct diameter > 10 mm (P = 0.023); duration of stent placement > 1 mo (P = 0.007); use of straight-type stents (P < 0.001); and 10-Fr sized stents (P < 0.001). Retrieval of the migrated stents was successful in all cases. The grasping technique, using a basket or snare, was effective for pig-tailed or thin and straight stents, whereas the guidewire cannulation technique was effective for thick and straight stents.
CONCLUSION: Migration of tube stents within the bile duct is rare but possible, and it is important to determine the risk factors involved in stent migration.
doi:10.3748/wjg.v20.i5.1318
PMCID: PMC3921514  PMID: 24574806
Migration; Endoscopic biliary stent; Risk factor; Endoscopic retrograde cholangiopancreatography; Retrieval
11.  A Case of a Giant Growing Serous Cystic Neoplasm of the Pancreas 
Case Reports in Oncology  2014;7(1):47-51.
Because of the widespread use of diagnostic imaging in recent years, serous cystic neoplasm (SCN) of the pancreas can often be detected even when small in diameter. SCNs are usually benign, but it is important to differentiate them from other types of cystic tumors. We report a case of a giant growing SCN that posed a challenge in differential diagnosis.
doi:10.1159/000358048
PMCID: PMC3934618  PMID: 24575016
Serous cystic neoplasm; Pancreas; Giant size; Diagnosis
12.  Effect of surrounding texture on the pursuit-pursuing illusion 
i-Perception  2014;5(1):20-40.
The pursuit-pursuing illusion is a visual illusion where a circular object placed in the centre of a radial pattern consisting of thin sectors is seen to move in the pursuit eye movement direction. The present study investigates the role of the surrounding texture, replacing the sectors with random dots or stripes in an orientation that was orthogonal, parallel or oblique to the pursuit direction. The experiments demonstrate that the acquired illusory effect was large for the orthogonal stripes. However, each surrounding texture produces a relatively smaller effect than the radial sectors. These results suggest that a hypothesis based on the property of a centre-surround relative-motion detector cannot fully explain the illusion and that the radial stimulus structure itself plays an important role in this illusion.
doi:10.1068/i0597
PMCID: PMC4130505  PMID: 25165514
motion illusion; smooth pursuit; eye movement; relative motion
13.  Effects of Angiotensin II Type 1 receptor blocker and adiponectin on adipocyte dysfunction in stroke-prone spontaneously hypertensive rats 
Background
Hypoadiponectinemia in lipoatrophy may be related to worsening of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). One of the beneficial effects of candesartan (Angiotensin II Type 1 receptor blocker) for preventing hypertension may be increasing of adiponectin due to improvement of adipocyte dysfunction. In this study, we determined the effects of candesartan or adiponectin on pathophysiologic features and adipocyte dysfunction in SHRSP.
Methods
Candesartan was administered to male SHRSP from 16 to 20 weeks of age (2 mg/kg/day). Adiponectin was cloned and intravenously administered to male SHRSP from 16 to 20 weeks of age. We examined biological parameters, as well as the expression and release of adipokines.
Results
The SHRSP exhibited severe atrophy of visceral fat and progression of severe hypertension. The expression and release of leptin and adiponectin were impaired at 6 and 20 weeks of age. Candesartan suppressed the development of lipoatrophy and reduced the incidence of stroke at 20 weeks of age. Candesartan also enhanced the expression of adiponectin and leptin by inducing the overexpression of peroxisome proliferator activated receptor γ. Circulating level of leptin was significantly higher in candesartan group than in the control group, whereas adiponectin was similar in both groups. Intravenous administration of adiponectin resulted in enhancement of adiponectin expression in adipose tissue, but no remarkable effects were found in pathophysiology in SHRSP.
Conclusions
Our results indicate that candesartan protects against hypertension and adipocyte dysfunction in SHRSP. The induction of leptin expression appeared to be important factor in the inhibition of stroke lesions, whereas adiponectin was not a major regulator of blood pressure in SHRSP with genetic hypertension. Further studies are needed to elucidate the role of the renin–angiotensin system in adipose tissue dysfunction in relation to hypertensive end-organ damage.
doi:10.1186/1476-511X-12-108
PMCID: PMC3750705  PMID: 23876211
Stroke-prone spontaneously hypertensive rats; Adipose tissue; Renin–angiotensin system; Angiotensin II type I receptor blocker; Lipoatrophy; Adipokines
14.  The Prevalence of the Risk Factors for Atherosclerosis among Type 2 Diabetic Patients Is Greater in the Progressive Stages of Chronic Kidney Disease 
Nephron Extra  2013;3(1):66-72.
Background/Aims
The prevalence of the risk factors for atherosclerosis, other than diabetes mellitus, among type 2 diabetic patients with different stages of chronic kidney disease (CKD) determined by glomerular filtration rate (GFR) was investigated.
Methods
The prevalence of ten risk factors (age ≥65 years, history of smoking, male gender, obesity, albuminuria, hypertension, hypercholesterolemia, hypo-HDL-cholesterolemia, hyperuricemia and anemia) was determined in 2,107 Japanese type 2 diabetic patients with different stages of CKD (six stages according to GFR).
Results
The risk factors for age ≥65 years and male gender were found in 49 and 62% of the study subjects, respectively. The percentages of subjects with a current history of smoking, obesity, albuminuria, hypertension, hypercholesterolemia, hypo-HDL-cholesterolemia, hyperuricemia and anemia were 35, 44, 47, 70, 61, 13, 21 and 26%, respectively. The prevalence of age ≥65 years, male gender, albuminuria, hypertension, hypo-HDL-cholesterolemia, hyperuricemia and anemia was greater in the later stages of GFR, whereas the prevalence of hypercholesterolemia and obesity did not differ between stages. The prevalence of a current history of smoking was lower in the later stages of GFR. The cumulative number of risk factors increased from 3.1 to 6.8 in the later stages of GFR.
Conclusion
Among type 2 diabetic patients with CKD, the total number of risk factors increases with the progression of renal dysfunction. It is important to pay attention to newly recognized risk factors for hyperuricemia and anemia, in addition to hypertension, albuminuria and hypo-HDL-cholesterolemia, in monitoring diabetic patients with later stages of CKD.
doi:10.1159/000353592
PMCID: PMC3728600  PMID: 23904855
Chronic kidney disease; Hyperuricemia; Atherosclerosis; Anemia; Diabetic nephropathy
15.  Vildagliptin is Effective for Glycemic Control in Diabetic Patients Undergoing either Hemodialysis or Peritoneal Dialysis 
Diabetes Therapy  2013;4(2):321-329.
Introduction
Vildagliptin can be used in patients with type 2 diabetes mellitus and renal impairment. However, there have been few reports investigating the clinical effectiveness of vildagliptin in diabetic patients undergoing hemodialysis. No previous studies have evaluated the use of vildagliptin in patients undergoing peritoneal dialysis. The authors determined the usefulness of vildagliptin for treating type 2 diabetic patients receiving chronic dialysis, including peritoneal dialysis.
Methods
A retrospective study of ten diabetic patients undergoing peritoneal dialysis and five diabetic patients undergoing hemodialysis who were treated with 50 mg/day of vildagliptin was performed. Clinical parameters were investigated for a period of 6 months starting from the vildagliptin therapy.
Results
The hemoglobin A1c (HbA1c) levels were significantly reduced after baseline in both the peritoneal dialysis and hemodialysis groups, whereas the hemoglobin levels did not change during the follow-up period. The mean change in the HbA1c level (ΔHbA1c) was −0.6 ± 0.9% and −0.5 ± 0.7% among the patients undergoing peritoneal dialysis and hemodialysis, respectively. The glycated albumin (GA) levels were also significantly reduced compared with baseline in the peritoneal dialysis group, although the serum albumin levels did not change. The mean change in the GA level (ΔGA) was −3.4 ± 3.1% and −2.1 ± 2.5% among the patients undergoing peritoneal dialysis and hemodialysis, respectively. Stepwise multivariate analyses demonstrated the level of HbA1c at baseline to be significantly associated with the ΔHbA1c and that the level of GA at baseline was significantly associated with the ΔGA.
Conclusion
Vildagliptin exhibits effectiveness in patients with type 2 diabetes mellitus undergoing peritoneal dialysis or hemodialysis. The degree of improvement in the HbA1c and GA levels was dependent on these levels at baseline, similar to the findings of previous reports of subjects without end-stage kidney disease.
doi:10.1007/s13300-013-0029-8
PMCID: PMC3889330  PMID: 23801219
Diabetes; End-stage kidney disease; Hemodialysis; Hemoglobin A1c; Glycated albumin; Peritoneal dialysis; Renal impairment; Type 2 diabetes mellitus; Vildagliptin
16.  Synchronous pancreatic solid pseudopapillary neoplasm and intraductal papillary mucinous neoplasm 
Solid pseudopapillary neoplasm (SPN) is a rare and low-grade malignant pancreatic neoplasm composed of poorly cohesive monomorphic neoplastic cells forming solid and pseudopapillary structures with frequent hemorrhagic-cystic degeneration. Intraductal papillary mucinous neoplasm (IPMN) is a pancreatic exocrine tumor composed of intraductal papillary growth of mucin containing neoplastic cells in the main pancreatic duct or its major branches. In the case presented here, a 53-year-old, Japanese man was found to have multiple cystic lesions and dilatation of the main pancreatic duct in the neck of the pancreas. Histological examination revealed a main-duct and branch-duct type IPMN, of the gastric-type, involving the neck of the pancreas, associated with a 0.5 cm SPN in the caudal side of the IPMN. We diagnosed this case as synchronous SPN and IPMN. As far as we know, only one other case of synchronous SPN and IPMN has been reported. Both the present case and the previously reported case showed abnormal nuclear expression of β-catenin in SPN, whereas IPMN showed no abnormal nuclear expression. These results suggest that β-catenin abnormality is not a common pathogenetic factor of synchronous SPN and IPMN.
doi:10.3748/wjg.v19.i21.3358
PMCID: PMC3671091  PMID: 23745041
Intraductal papillary mucinous neoplasms; Solid pseudopapillary neoplasms; Pancreatic neoplasms; Synchronous neoplasms; Pancreas; Beta-catenin
17.  A short line segment squirms along a zigzag line 
i-Perception  2013;4(2):141-143.
When a short straight line segment moves across a zigzag line and is viewed in one's peripheral vision, it appears to exhibit nonrigid squirming motion (the squirm effect). This phenomenon demonstrates that the form, orientation, and motion direction of a short line are influenced by those of a longer one when they are viewed in one's peripheral vision.
doi:10.1068/i0573sas
PMCID: PMC3677334  PMID: 23755359
motion illusion; motion streak; line orientation; motion direction; corner detection; assimilation
18.  A Case of Successful Placement of a Fully Covered Metallic Stent for Hemobilia Secondary to Hepatocellular Carcinoma with Bile Duct Invasion 
Case Reports in Oncology  2012;5(3):682-686.
Hemobilia represents gastrointestinal bleeding that develops as a result of communication between blood vessels and the biliary tract, which causes the blood to reach the duodenal papilla. It is characterized by biliary colic as the initial symptom, and the complications of cholangitis, obstructive jaundice and/or anemia. In general, definitive diagnosis is made by esophagogastroduodenoscopy which confirms bleeding from the duodenal papilla. Abdominal US and abdominal enhanced CT are performed to identify the source of the bleeding, as well as ERCP for biliary drainage to control the comorbid cholangitis. If active hemorrhage accompanied by worsening of the anemia is suspected, abdominal angiography is performed to selectively image the hepatic artery. Then, embolization of the culprit vessel is recommended. In our patients with difficult hemostasis, because of the direct compression hemostasis to the tumor site achieved with the fully covered metallic stent and secondary compression hemostasis due to blood clots, the bleeding could be controlled.
doi:10.1159/000346341
PMCID: PMC3551402  PMID: 23341812
Hemobilia; Hepatocellular carcinoma; Bile duct invasion; Fully covered metallic
19.  Small serotonin-positive pancreatic endocrine tumors caused obstruction of the main pancreatic duct 
We report 2 cases of pancreatic endocrine tumors that caused obstruction of the main pancreatic duct (MPD). A 49-year-old asymptomatic man was referred to our institution because dilation of the MPD was revealed by abdominal ultrasonography (US). No tumor was detected by endoscopic ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). The diameter of the MPD was > 20 mm at the body, and no dilation was noted at the head. Although malignancy was not confirmed through cytology or imaging, pancreatic cancer was strongly suspected. Pancreaticoduo- denectomy was performed. Pathological and immunohistochemical examination revealed a 5 mm × 3 mm serotonin-positive endocrine tumor. Fibrosis was present around the MPD and seemed to cause stricture. A 32-year-old asymptomatic man had elevated serum amylase, and US demonstrated dilation of the MPD. No tumor was detected by CT and MRI. Pancreatic cancer was suspected due to stricture and dilation of the MPD. Pancreatectomy of middle part of pancreas was performed. Pathological and immunohistochemical examination revealed a serotonin-positive endocrine tumor sized 5 mm × 4 mm. We report 2 cases of serotonin-positive pancreatic endocrine tumors that caused stricture of the MPD in spite of the small size of the tumor.
doi:10.3748/wjg.v18.i45.6669
PMCID: PMC3516203  PMID: 23236243
Serotonin; Pancreatic endocrine tumor; Main pancreatic duct; Obstruction; Dilatation
20.  Prolonged hyperinsulinemia after subcutaneous injection of 2400 U regular insulin in a suicide attempt: Time course of serum insulin with frequent measurements 
Abstract
We studied the time course of serum insulin level in a patient who injected large amounts of regular insulin in an attempted suicide. A 58‐year‐old woman attempted suicide by subcutaneously injecting herself with 2400 U regular insulin. On arrival, the serum glucose level was 2.4 mmol/L (44 mg/dL) and the serum insulin level was 40,000 pmol/L (5700 μIU/mL). The serum insulin level was high, with a maximum of 110,000 pmol/L (16,000 μIU/mL) at 13 h after injection, followed by an initial rapid decrease and a subsequent slow decrease, with hyperinsulinemia lasting as long as 5 days after injection. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00211.x, 2012)
doi:10.1111/j.2040-1124.2012.00211.x
PMCID: PMC4019248  PMID: 24843608
Hyperinsulinemia; Hypoglycemia; Insulin
21.  Hypertension resistant to antihypertensive agents commonly occurs with the progression of diabetic nephropathy in Japanese patients with type 2 diabetes mellitus: a prospective observational study 
BMC Nephrology  2012;13:48.
Background
We investigated 1) the frequency of hypertension in patients with type 2 diabetes graded by the new classification of chronic kidney disease (CKD) reported by the Kidney Disease: Improving Global Outcomes (KDIGO) and 2) the number of antihypertensive agents needed to achieve treatment goals using a prospective observational study.
Methods
A population of 2018 patients with type 2 diabetes mellitus was recruited for the study. The CKD stage was classified according to the eGFR and the urinary albumin excretion levels.
Results
Hypertension was found in 1420 (70%) of the patients, and the proportion of subjects showing a blood pressure < 130/80 mmHg was 31% at the baseline. Although the mean blood pressure was approximately 130/75 mmHg, the rate of patients with a blood pressure of < 130/80 mmHg became limited to 41-50% during the observation period. The number of antihypertensive agents required for treatment was significantly higher at the endpoint (2.0 ± 1.3) than at the baseline (1.6 ± 1.2). Furthermore, it increased with the progression of the CKD stage at both the baseline and the endpoint of the observation. However, the frequency of subjects who did not achieve the blood pressure target was found to increase in the group demonstrating the later stage of CKD.
Conclusions
Hypertension resistant to antihypertensive agents was common in the patients with type 2 diabetes mellitus and increased with the progression of CKD. Although powerful combination therapy using antihypertensive agents is considered necessary for the strict control of blood pressure, this became difficult in individuals who were in advanced stages as graded based on the eGFR and the urinary albumin excretion levels.
doi:10.1186/1471-2369-13-48
PMCID: PMC3437202  PMID: 22738384
Hypertension; Antihypertensive agents; Chronic kidney disease; CKD stage; Type 2 diabetes mellitus; KDIGO
22.  Randomized controlled trial of pancreatic stenting to prevent pancreatitis after endoscopic retrograde cholangiopancreatography 
AIM: To determine the effectiveness of pancreatic duct (PD) stent placement for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high risk patients.
METHODS: Authors conducted a single-blind, randomized controlled trial to evaluate the effectiveness of a pancreatic spontaneous dislodgement stent against post-ERCP pancreatitis, including rates of spontaneous dislodgement and complications. Authors defined high risk patients as having any of the following: sphincter of Oddi dysfunction, difficult cannulation, prior history of post-ERCP pancreatitis, pre-cut sphincterotomy, pancreatic ductal biopsy, pancreatic sphincterotomy, intraductal ultrasonography, or a procedure time of more than 30 min. Patients were randomized to a stent group (n = 60) or to a non-stent group (n = 60). An abdominal radiograph was obtained daily to assess spontaneous stent dislodgement. Post-ERCP pancreatitis was diagnosed according to consensus criteria.
RESULTS: The mean age (± standard deviation) was 67.4 ± 13.8 years and the male: female ratio was 68:52. In the stent group, the mean age was 66 ± 13 years and the male: female ratio was 33:27, and in the non-stent group, the mean age was 68 ± 14 years and the male: female ratio was 35:25. There were no significant differences between groups with respect to age, gender, final diagnosis, or type of endoscopic intervention. The frequency of post-ERCP pancreatitis in PD stent and non-stent groups was 1.7% (1/60) and 13.3% (8/60), respectively. The severity of pancreatitis was mild in all cases. The frequency of post-ERCP pancreatitis in the stent group was significantly lower than in the non-stent group (P = 0.032, Fisher’s exact test). The rate of hyperamylasemia were 30% (18/60) and 38.3% (23 of 60) in the stent and non-stent groups, respectively (P = 0.05, χ2 test). The placement of a PD stent was successful in all 60 patients. The rate of spontaneous dislodgement by the third day was 96.7% (58/60), and the median (range) time to dislodgement was 2.1 (2-3) d. The rates of stent migration, hemorrhage, perforation, infection (cholangitis or cholecystitis) or other complicationss were 0% (0/60), 0% (0/60), 0% (0/60), 0% (0/60), 0% (0/60), respectively, in the stent group. Univariate analysis revealed no significant differences in high risk factors between the two groups. The pancreatic spontaneous dislodgement stent safely prevented post-ERCP pancreatitis in high risk patients.
CONCLUSION: Pancreatic stent placement is a safe and effective technique to prevent post-ERCP pancreatitis. Therefore authors recommend pancreatic stent placement after ERCP in high risk patients.
doi:10.3748/wjg.v18.i14.1635
PMCID: PMC3325530  PMID: 22529693
Endoscopic retrograde cholangiopancreatography; Pancreatitis; Postoperative complications; Prophylaxis; Stents
23.  Illusory object motion in the centre of a radial pattern: The Pursuit–Pursuing illusion 
i-Perception  2012;3(1):59-87.
A circular object placed in the centre of a radial pattern consisting of thin sectors was found to cause a robust motion illusion. During eye-movement pursuit of a moving target, the presently described stimulus produced illusory background-object motion in the same direction as that of the eye movement. In addition, the display induced illusory stationary perception of a moving object against the whole display motion. In seven experiments, the characteristics of the illusion were examined in terms of luminance relationships and figural characteristics of the radial pattern. Some potential explanations for these findings are discussed.
doi:10.1068/i0430
PMCID: PMC3485812  PMID: 23145267
Visual illusion; motion perception; smooth pursuit; equiluminance; radial pattern; illusory motion
24.  Hyperuricemia Is Independently Associated with Coronary Heart Disease and Renal Dysfunction in Patients with Type 2 Diabetes Mellitus 
PLoS ONE  2011;6(11):e27817.
Aims
To investigate the relationship between hyperuricemia (HUA) and the clinical backgrounds in Japanese patients with type 2 diabetes mellitus.
Methods
After a cross-sectional study evaluating the association of HUA with the clinical characteristics in 1,213 patients with type 2 diabetes mellitus, the estimated glomerular filtration rate (eGFR) and the incidence of diabetic macroangiopathies was investigated in a prospective observational study in 1,073 patients during a 3.5 year period. HUA was defined by serum uric acid levels >327 μmol/L or as patients using allopurinol.
Results
The frequency of HUA was significantly higher in the diabetic patients (32% in men and 15% in women) than in the normal controls (14% in men and 1% in women). In total, HUA was found in 299 (25%) of the patients during the cross-sectional study. Even after adjusting for sex, drinking status, treatment for diabetes mellitus, body mass index, hypertension, use of diuretics, hyperlipidemia, HbA1c and/or the eGFR, the HUA was independently associated with some diabetic complications. The eGFR was significantly reduced in HUA patients compared to those with normouricemia in the 12 months after observation was started. HUA was also an independent risk factor for coronary heart disease even after adjustment in the Cox proportional hazard model.
Conclusions
HUA is a associated with diabetic micro- and macroangiopathies. HUA is a predictor of coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitus. However, the influence of HUA is considered to be limited.
doi:10.1371/journal.pone.0027817
PMCID: PMC3220675  PMID: 22125626
25.  Mild anemia is frequent and associated with micro‐ and macroangiopathies in patients with type 2 diabetes mellitus 
Abstract
Aims/Introduction:  The present study investigated the frequency of mild anemia, which is not an indication of intensive therapy using drugs, in Japanese patients with type 2 diabetes mellitus and the association of mild anemia with diabetic complications.
Materials and Methods:  This is a cross‐sectional study of 1189 patients with type 2 diabetes mellitus. Anemia was defined as a hemoglobin level <13.5 g/dL in men and <12.0 g/dL in women. The patients with anemia were divided into two groups: (i) grade 1 anemia with a hemoglobin level ≥11.0 g/dL; and (ii) grade 2 anemia with a hemoglobin level <11.0 g/dL.
Results:  The prevalence of anemia increased with the progression of the stage of diabetic nephropathy and chronic kidney disease. The frequencies of diabetic micro‐ and macroangiopathies increased with the progression of anemia among 798 patients without anemia, 300 with grade 1 anemia and 91 with grade 2 anemia. Both grade 1 and grade 2 anemia were associated with diabetic micro‐ and macroangiopathies. They remained independently associated with diabetic retinopathy, coronary heart disease and peripheral arterial disease after adjustment by age, sex, body mass index, use of angiotensin II receptor blocker, estimated glomerular filtration rate and stage of diabetic nephropathy.
Conclusions:  Mild anemia is frequent and associated with micro‐ and macroangiopathies in patients with type 2 diabetes mellitus. It is important to carry out intensive examinations for the detection of diabetic micro‐ and macroangiopathies in addition to evaluating the causes of anemia when mild anemia is found in patients with diabetes mellitus. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00060.x, 2010)
doi:10.1111/j.2040-1124.2010.00060.x
PMCID: PMC4014891  PMID: 24843443
Anemia; eGFR; Diabetic nephropathy

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