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1.  Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension 
Hypertension is one of the major risk factors for cardiovascular and cerebrovascular disease and mortality. Patients who receive insufficient doses of antihypertensive agents or who are poorly adherent to multidrug treatment regimens often fail to achieve adequate blood pressure (BP) control. The aim of this study was to determine the efficacy of an angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) combination tablet containing a regular dose of irbesartan (100 mg) and a high dose of amlodipine (10 mg) with regard to lowering BP and other risk factors for cardiovascular disease.
We retrospectively evaluated data from 68 patients with essential hypertension whose treatment regimen was changed either from combination treatment with an independent ARB and a low-dose or regular-dose CCB or from a combination tablet of ARB and a low-dose or regular-dose CCB to a combination tablet containing amlodipine 10 mg and irbesartan 100 mg, because of incomplete BP control. Previous treatments did not include irbesartan as the ARB.
The combination tablet decreased systolic and diastolic BP. In addition, it significantly decreased serum uric acid, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol levels, independent of the BP-lowering effect. Treatment with the combination tablet did not affect serum triglycerides, plasma glucose, glycated hemoglobin, serum potassium or creatinine levels, or the urinary albumin excretion rate.
The combination tablet containing amlodipine 10 mg and irbesartan 100 mg had a greater BP-lowering effect than an ARB and a low-dose or regular-dose CCB. In addition, the combination tablet had more favorable effects on serum uric acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels in patients with hypertension.
PMCID: PMC4296916  PMID: 25624765
blood pressure; combination tablet; uric acid; low-density lipoprotein cholesterol; high-density lipoprotein cholesterol
2.  Rare combination of familial adenomatous polyposis and gallbladder polyps 
World Journal of Gastroenterology : WJG  2014;20(46):17661-17665.
Familial adenomatous polyposis is associated with a high incidence of malignancies in the upper gastrointestinal tract (particularly ampullary adenocarcinomas). However, few reports have described a correlation between familial adenomatous polyposis and gallbladder neoplasms. We present a case of a 60-year-old woman with familial adenomatous polyposis who presented with an elevated mass in the neck of the gallbladder (measuring 16 mm × 8 mm in diameter) and multiple small cholecystic polyps. She had undergone a total colectomy for ascending colon cancer associated with familial adenomatous polyposis 22 years previously. The patient underwent laparoscopic cholecystectomy under a preoperative diagnosis of multifocal gallbladder polyps. Pathologic examination of the resected gallbladder revealed more than 70 adenomatous lesions, a feature consistent with adenoma of the gallbladder. This case suggests a requirement for long-term surveillance of the biliary system in addition to the gastrointestinal tract in patients with familial adenomatous polyposis.
PMCID: PMC4265629  PMID: 25516682
Adenoma; Adenomatous polyposis coli; Biliary system; Familial adenomatous polyposis; Gallbladder polyp
3.  Receptor-like cytoplasmic kinases are pivotal components in pattern recognition receptor-mediated signaling in plant immunity 
Plant Signaling & Behavior  2013;8(10):e25662.
Innate immunity is generally initiated with recognition of conserved pathogen-associated molecular patterns (PAMPs). PAMPs are perceived by pattern recognition receptors (PRRs), leading to activation of a series of immune responses, including the expression of defense genes, ROS production and activation of MAP kinase. Recent progress has indicated that receptor-like cytoplasmic kinases (RLCKs) are directly activated by ligand- activated PRRs and initiate pattern -triggered immunity (PTI) in both Arabidopsis and rice. To suppress PTI, pathogens inhibit the RLCKs by many types of effectors, including AvrAC, AvrPphB and Xoo1488. In this review, we summarize recent advances in RLCK-mediated PTI in plants.
PMCID: PMC4091068  PMID: 23857358
RLCK; PRR; MAPK; immunity; PAMP
4.  Stapled gastro/duodenojejunostomy shortens reconstruction time during pylorus-preserving pancreaticoduodenectomy 
AIM: To investigate whether a stapled technique is superior to the conventional hand-sewn technique for gastro/duodenojejunostomy during pylorus-preserving pancreaticoduodenectomy (PpPD).
METHODS: In October 2010, we introduced a mechanical anastomotic technique of gastro- or duodenojejunostomy using staplers during PpPD. We compared clinical outcomes between 19 patients who underwent PpPD with a stapled gastro/duodenojejunostomy (stapled anastomosis group) and 19 patients who underwent PpPD with a conventional hand-sewn duodenojejunostomy (hand-sewn anastomosis group).
RESULTS: The time required for reconstruction was significantly shorter in the stapled anastomosis group than in the hand-sewn anastomosis group (186.0 ± 29.4 min vs 219.7 ± 50.0 min, P = 0.02). In addition, intraoperative blood loss was significantly less (391.0 ± 212.0 mL vs 647.1 ± 482.1 mL, P = 0.03) and the time to oral intake was significantly shorter (5.4 ± 1.7 d vs 11.3 ± 7.9 d, P = 0.002) in the stapled anastomosis group than in the hand-sewn anastomosis group. There were no differences in the incidences of delayed gastric emptying and other postoperative complications between the groups.
CONCLUSION: These results suggest that stapled gastro/duodenojejunostomy shortens reconstruction time during PpPD without affecting the incidence of delayed gastric emptying.
PMCID: PMC3882414  PMID: 24409068
Pylorus-preserving pancreaticoduodenectomy; Stapled anastomosis; Gastrojejunostomy; Duodenojejunostomy; Delayed gastric emptying
5.  Prognostic Impact of Hyaluronan and Its Regulators in Pancreatic Ductal Adenocarcinoma 
PLoS ONE  2013;8(11):e80765.
Although pancreatic ductal adenocarcinoma is characterized by an abundant stroma enriched with hyaluronan (HA), the prognostic impact of HA and its regulators remains unknown.
Using immunohistochemistry, expression patterns of HA and its regulators, including a synthesizing enzyme (HAS2), and a degrading enzyme (HYAL1) were investigated in patients who received surgical resection. The prognostic significance of these markers and other clinicopathological variables was determined using univariate and multivariate analyses. The HA levels were determined quantitatively by enzyme-linked immunosorbent assay (ELISA).
We found that strong expressions of HA (P=0.008) and HAS2 (P=0.022) were significantly associated with shorter survival time after surgery. By contrast, weak expression of HYAL1 was significantly associated with poor survival (P=0.001). In multivariate analysis, tumor stage (hazard ratio (HR)=2.76, 95% confidence interval (CI): 1.14-6.66 P=0.024), strong HA expression (HR=6.04, 95%CI: 1.42-25.69 P=0.015), and weak HYAL1 expression (HR=3.16, 95%CI: 1.19-8.40 P=0.021) were independent factors predicting poor survival. ELISA revealed higher concentration of HA in pancreatic cancer tissues than in normal pancreatic tissues (P=0.001).
These findings suggest, for the first time, that HA and its regulators may have prognostic impact in patients with pancreatic cancer.
PMCID: PMC3823618  PMID: 24244714
6.  Reticulon 4B (Nogo-B) Is a Novel Regulator of Hepatic Fibrosis 
Hepatology (Baltimore, Md.)  2011;53(4):1306-1315.
Nogo-B, also known as Reticulon 4B, plays important roles in vascular injuries. Its function in the liver is not understood. The aim of this study was to characterize Nogo-B in liver fibrosis and cirrhosis. Nogo-B distribution was assessed in normal and cirrhotic human liver sections. We also determined the levels of liver fibrosis in wild-type (WT) and Nogo-A/B knockout (NGB KO) mice after sham operation or bile duct ligation (BDL). To investigate the mechanisms of Nogo-B’s involvement in fibrosis, hepatic stellate cells were isolated from WT and NGB KO mice and transformed into myofibroblasts. Portal pressure was measured to test whether Nogo-B gene deletion could ameliorate portal hypertension. In normal livers, Nogo-B expression was found in nonparenchymal cells, whereas its expression in hepatocytes was minimal. Nogo-B staining was significantly elevated in cirrhotic livers. Fibrosis was significantly increased in WT mice 4 weeks after BDL compared with NGB KO mice. The absence of Nogo-B significantly reduced phosphorylation of Smad2 levels upon transforming growth factor β (TGF-β) stimulation. Reconstitution of the Nogo-B gene into NGB KO fibroblasts restored Smad2 phosphorylation. Four weeks after BDL, portal pressure was significantly increased in WT mice by 47%, compared with sham-operated controls (P = 0.03), whereas such an increase in portal pressure was not observed in NGB KO mice (P = NS).
Nogo-B regulates liver fibrosis, at least in part, by facilitating the TGFβ/Smad2 signaling pathway in myofibroblasts. Because absence of Nogo-B ameliorates liver fibrosis and portal hypertension, Nogo-B blockade may be a potential therapeutic target in fibrosis/cirrhosis.
PMCID: PMC3667398  PMID: 21480333
7.  Laparoscopic colectomy for transverse colon cancer in an automated peritoneal dialysis patient: A case report 
To date, intra-abdominal surgery in patients undergoing peritoneal dialysis (PD) has been considered to be associated with increased risk even when it is performed laparoscopically. To our knowledge, this is the first case of laparoscopic colectomy for transverse colon cancer in a patient undergoing automated PD (APD).
A 67-year-old man undergoing APD for end-stage chronic renal failure secondary to diabetic nephropathy was diagnosed with transverse colon cancer. Laparoscopic tumor resection without removal of the PD catheter was performed uneventfully. After surgery, PD was interrupted for 4 weeks and then safely resumed after confirming no severe complications of anastomotic leakage or intra-abdominal abscess.
In patients undergoing PD, the safety of laparoscopic surgery without removal of the catheter and the optimal timing of resuming postoperative PD with or without temporary hemodialysis remain controversial.
We believe that laparoscopic colectomy can be safely performed in patients undergoing PD. Further case reports and investigations on this procedure with special reference to safety are warranted in future.
PMCID: PMC3679433  PMID: 23706995
Peritoneal dialysis; Colon cancer; Laparoscopic surgery
8.  Synchronous Occurrence of Advanced Neuroendocrine Carcinoma and Tubular Adenocarcinoma of the Rectum 
Case Reports in Gastroenterology  2013;7(1):117-121.
This report presents a rare case with the synchronous occurrence of advanced neuroendocrine carcinoma (NEC) and tubular adenocarcinoma of the rectum. A 52-year-old Japanese male presented with general fatigue and bloody stool. Endoscopic examination showed an ulcerated lesion of the lower rectum. The pathological diagnosis of biopsy specimens from this lesion indicated moderately differentiated adenocarcinoma. He was referred to the surgical outpatient clinic with advanced rectal cancer. Barium enema indicated two lesions in the upper and lower rectum. Computed tomography revealed multiple hepatic metastases. A low anterior resection was performed with lymph node dissection. The resected specimen indicated an elevated lesion with ulceration in the upper rectum and an ulcerated lesion in the lower rectum. Histopathological and immunohistochemical analyses revealed NEC from the upper rectum and moderately differentiated tubular adenocarcinoma from the lower rectum. These two lesions were completely separated from each other. Therefore, this case demonstrates the synchronous occurrence of advanced NEC and tubular adenocarcinoma in the rectum.
PMCID: PMC3617976  PMID: 23626511
Neuroendocrine carcinoma; Small cell type; Tubular adenocarcinoma; Synchronous occurrence; Rectum
9.  Synchronous Sporadic Gastrointestinal Stromal Tumors in the Stomach and Jejunum: Report of a Case 
This report describes a patient with synchronous sporadic gastrointestinal stromal tumors (GISTs) in the stomach and jejunum. A 71-year-old Japanese male presented with a 2-year history of occasional melena and general fatigue. Computed tomography of the abdomen demonstrated an enhanced extramural gastric tumor, 4 cm in diameter. Endoscopic examination revealed a jejunal submucosal tumor. He was referred to the surgical outpatient clinic for surgical treatment of an extramural gastric tumor and a jejunal submucosal tumor. Laparotomy allowed the identification of a nut-sized extramural tumor at the stomach and a thumb's head-sized tumor on the jejunum. Partial resections of the stomach and jejunum were performed. Histopathological and immunohistochemical examination revealed that these tumors were GISTs. Although no molecular analysis was performed, the immunohistochemical staining patterns of these two tumors were different from each other. Therefore, the final diagnosis was synchronous sporadic GISTs in the stomach and jejunum. This patient has survived without recurrence for approximately 12 years since complete resection.
PMCID: PMC3617895  PMID: 23626506
Gastrointestinal stromal tumor; Sporadic; Synchronous; Stomach; Jejunum
10.  The type III inositol 1,4,5-trisphosphate receptor is associated with aggressiveness of colorectal carcinoma☆ 
Cell calcium  2010;48(6):315-323.
The inositol 1,4,5-trisphosphate receptor (InsP3R) mediates Ca2+ signaling in epithelia and regulates cellular functions such as secretion, apoptosis and cell proliferation. Loss of one or more InsP3R isoform has been implicated in disease processes such as cholestasis. Here we examined whether gain of expression of InsP3R isoforms also may be associated with development of disease. Expression of all three InsP3R isoforms was evaluated in tissue from colorectal carcinomas surgically resected from 116 patients. Type I and II InsP3Rs were seen in both normal colorectal mucosa and colorectal cancer, while type III InsP3R was observed only in colorectal cancer. Type III InsP3R expression in the advancing margins of tumors correlated with depth of invasion, lymph node metastasis, liver metastasis, and TNM stage. Heavier expression of type III InsP3R also was associated with decreased 5-year survival. shRNA knockdown of type III InsP3R in CACO-2 colon cancer cells enhanced apoptosis, while over-expression of the receptor decreased apoptosis. Thus, type III InsP3R becomes expressed in colon cancer, and its expression level is directly related to aggressiveness of the tumor, which may reflect inhibition of apoptosis by the receptor. These findings suggest a previously unrecognized role for Ca2+ signaling via this InsP3R isoform in colon cancer.
PMCID: PMC3572849  PMID: 21075448
Inositol 1,4,5-trisphosphate receptor; Calcium signaling; Colorectal cancer; Prognosis; Apoptosis
11.  Laparoscopic cecal cancer resection in a patient with a ventriculoperitoneal shunt: A case report 
The presence of a ventriculoperitoneal shunt has been considered to be a contraindication for laparoscopic surgery till date; however, laparoscopic cholecystectomy was recently reported as safe for patients with this shunt.
We present the first case, to the best of our knowledge, of laparoscopic colectomy for cecal cancer in a patient with a ventriculoperitoneal shunt. A 59-year-old woman with a ventriculoperitoneal shunt for hydrocephalus was referred to our hospital with cecal cancer. Laparoscopic cecal cancer resection was performed successfully and uneventfully by manipulating the shunt.
Clamping of the shunt catheter at the subcutaneous region was performed before insufflation of carbon dioxide to prevent adverse effects from the pneumoperitoneum.
We believe that laparoscopic colectomy for colon cancer can be performed safely in patients with a ventriculoperitoneal shunt by optimal manipulation of the shunt.
PMCID: PMC3604664  PMID: 23416501
Ventriculoperitoneal shunt; Colon cancer; Laparoscopic surgery
12.  Intestinal Obstruction due to Complete Transmural Migration of a Retained Surgical Sponge into the Intestine 
Case Reports in Gastroenterology  2012;6(3):754-759.
A 56-year-old woman with a history of gynecological surgery for cervical cancer 18 years previously was referred to our hospital for colicky abdominal pain, nausea and vomiting. Intestinal obstruction was diagnosed by contrast-enhanced computed tomography (CT) which showed dilation of the small intestine and suggested obstruction in the terminal ileum. In addition, CT showed a thick-walled cavitary lesion communicating with the proximal jejunum. 18F-fluorodeoxyglucose positron emission tomography showed abnormal uptake at the same location as the cavitary lesion revealed by CT. The patient underwent laparotomy for the ileus and resection of the cavitary lesion. At laparotomy, we found a retained surgical sponge in the ileum 60 cm from the ileocecal valve. The cavitary tumor had two fistulae communicating with the proximal jejunum. The tumor was resected en bloc together with the transverse colon, part of the jejunum and the duodenum. Microscopic examination revealed fibrous encapsulation and foreign body giant cell reaction. Since a retained surgical sponge without radiopaque markers is extremely difficult to diagnose, retained surgical sponge should be considered in the differential diagnosis of intestinal obstruction in patients who have undergone previous abdominal surgery.
PMCID: PMC3551410  PMID: 23341797
Retained surgical sponge; Gossypiboma; Textiloma; Intestinal obstruction; Ileus
13.  Function of Arabidopsis SWAP70 GEF in immune response 
Plant Signaling & Behavior  2012;7(4):465-468.
In animals, major classes of Rho guanine nucleotide exchange factors (GEFs) possess a Dbl (diffuse B-cell lymphoma)- homology (DH) domain that functions as a GEF-catalytic domain. However, no GEFs with the DH domain had been identified in plants. Recently, we found that the rice homolog of human SWAP70, Oryza sative (Os) SWAP70, containing the DH domain, exhibited GEF activity toward the rice Rho GTPase OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice.1 Arabidopsis contains a single SWAP70 gene. A T-DNA insertion mutant of Arabidopsis SWAP70 was morphologically wild type. Measurement of in planta growth of Pseudomonas syringae DC3000 hrcC, a mutant incapable of type III effector delivery, revealed enhanced growth of the pathogen in the atswap70 mutant, indicating that AtSWAP70 is required for PAMP-triggered immunity. In addition, the atswap70 mutation reduced the RPM1-mediated hypersensitive response. These results suggested that AtSWAP70 plays a role in both PAMP- and effector-triggered immunity in Arabidopsis.
PMCID: PMC3419034  PMID: 22499172
GEF; Rop; GTPase; immunity; DH; defense; HR; PTI; ETI
14.  Development of perianal ulcer as a result of acute fulminant amoebic colitis 
We report a case of acute fulminant amoebic colitis that resulted in the development of a perianal ulcer in a 29-year-old Japanese homosexual man with acquired immunodeficiency syndrome (AIDS). The patient was admitted to our hospital with a persistent perianal abscess that was refractory to antibiotic therapy administered at another hospital. On admission, we observed a giant ulcer in the perianal region. At first, cytomegalovirus colitis was suspected by blood investigations. Ganciclovir therapy was initiated; however, the patient developed necrosis of the skin around the anus during therapy. We only performed end-sigmoidostomy and necrotomy to avoid excessive surgical invasion. Histopathological examination of the surgical specimen revealed the presence of trophozoite amoebae, indicating a final diagnosis of acute fulminant amoebic colitis. The patient’s postoperative course was favorable, and proctectomy of the residual rectum was performed 11 mo later. Amoebic colitis is one of the most severe complications affecting patients with AIDS. Particularly, acute fulminant amoebic colitis may result in a poor prognosis; therefore, staged surgical therapy as a less invasive procedure should be considered as one of the treatment options for these patients.
PMCID: PMC3442221  PMID: 23002352
Acute fulminant amoebic colitis; Perianal ulcer; Acquired immunodeficiency syndrome; Cytomegalovirus colitis; Staged surgery
15.  Gender disparities in the association between epicardial adipose tissue volume and coronary atherosclerosis: A 3-dimensional cardiac computed tomography imaging study in Japanese subjects 
Growing evidence suggests that epicardial adipose tissue (EAT) may contribute to the development of coronary artery disease (CAD). In this study, we explored gender disparities in EAT volume (EATV) and its impact on coronary atherosclerosis.
The study population consisted of 90 consecutive subjects (age: 63 ± 12 years; men: 47, women: 43) who underwent 256-slice multi-detector computed tomography (MDCT) coronary angiography. EATV was measured as the sum of cross-sectional epicardial fat area on CT images, from the lower surface of the left pulmonary artery origin to the apex. Subjects were segregated into the CAD group (coronary luminal narrowing > 50%) and non-CAD group.
EATV/body surface area (BSA) was higher among men in the CAD group than in the non-CAD group (62 ± 13 vs. 33 ± 10 cm3/m2, p < 0.0001), but did not differ significantly among women in the 2 groups (49 ± 18 vs. 42 ± 9 cm3/m2, not significant). Multivariate logistic analysis showed that EATV/BSA was the single predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors excluded were age, body mass index, hypertension, diabetes mellitus, and hyperlipidemia.
Increased EATV is strongly associated with coronary atherosclerosis in men.
PMCID: PMC3489699  PMID: 22963346
Atherosclerosis; Gender difference; Epicardial adipose tissue; Obesity
16.  The clinical usefulness of urinary N1,N12-diacetylspermine (DiAcSpm) levels as a tumor marker in patients with colorectal cancer 
Oncology Letters  2012;3(5):970-974.
The aim of this study was to evaluate the usefulness of urinary N1,N12-diacetylspermine (DiAcSpm) measured by the colloidal gold aggregation method as a tumor marker for colorectal cancer (CRC). The preoperative urine of 113 CRC patients was collected, and the urinary DiAcSpm was measured by a reagent kit for DiAcSpm determination based on colloidal gold aggregation using automatic biochemical analyzers. The urinary DiAcSpm levels significantly correlated with distant metastasis and Tumor-Node-Metastasis (TNM) stage. The positive rates of urinary DiAcSpm were significantly higher than those of serum carcinoembryonic antigen (CEA) or cancer antigen 19-9 (CA19-9) in stages 0+I, II, III and IV. The positive rates of urinary DiAcSpm were also significantly higher than those of serum CEA or CA19-9 in the early and advanced CRC groups according to the Japan Classification of Colorectal Cancer. Therefore, urinary DiAcSpm, measured by a reagent kit for DiAcSpm determination based on colloidal gold aggregation, may be useful as a non-invasive tumor marker in patients with CRC.
PMCID: PMC3389634  PMID: 22783374
N1,N12-diacetylspermine; DiAcSpm; urine; tumor marker; colorectal cancer
17.  Pancreatoduodenectomy for bile duct and ampullary cancer 
Pylorus-preserving pancreatoduodenectomy has become a standard operation for distal and middle bile duct cancers. Bile duct cancer typically extends longitudinally and invades vertically. It frequently metastasizes to the lymph nodes and infiltrates the perineural spaces. The presence of residual cancer in the bile duct stump and lymph node metastases are significant prognostic factors. Negative surgical margins and D2 lymph node dissection are necessary for curative resection. The clinical course after portal vein resection for bile duct cancer with portal vein invasion is better than that of non-resectable bile duct cancer. Portal vein resection can therefore be useful. The efficacy of prophylactic portal vein resection is unclear. We describe here our methods for performing pylorus-preserving pancreatoduodenectomy for bile duct cancer.
Electronic supplementary material
The online version of this article (doi:10.1007/s00534-011-0480-8) contains supplementary material, which is available to authorized users.
PMCID: PMC3311854  PMID: 22170385
Pancreatoduodenectomy; Bile duct cancer; Ampullary cancer; Lymph node dissection; Pancreaticojejunostomy
18.  Prognostic significance of monocarboxylate transporter 4 expression in patients with colorectal cancer 
Cancer cells generally have a high rate of glycolysis and produce larger quantities of lactate as compared to the surrounding normal cells. Monocarboxylate transporter 4 (MCT4) is one of the proton pumps exchanging the lactate through the plasma membrane. The prognostic significance of MCT4 expression has not been evaluated in patients with colorectal cancer (CRC). Surgical specimens from 105 CRC patients were immunohistochemically stained using a polyclonal anti-MCT4 antibody. The relationships among the MCT4 expression, clinicopathological factors and prognosis were evaluated. A total of 53 (50.5%) of the 105 patients with CRC were determined to have tumors positive for MCT4 expression. The expression of MCT4 significantly correlated with the tumor size, depth of invasion, lymph node metastasis, distant metastasis and TNM staging. The survival rate of the patients who were positive for MCT4 expression was significantly lower than that of patients with negative MCT4 expression. Positive MCT4 expression was a significantly poor prognostic factor, as determined by both univariate and multivariate analyses. Therefore, positive MCT4 expression appears to be a useful marker for tumor progression and prognosis in patients with CRC.
PMCID: PMC3438655  PMID: 22969839
monocarboxylate transporter; monocarboxylate transporter 4; colorectal cancer
19.  Identification of novel molecular markers for detection of gastric cancer cells in the peripheral blood circulation using genome-wide microarray analysis 
Although metastasis or relapse is a leading cause of death for patients with gastric cancer, the hematogenous spread of cancer cells remains undetected at the time of initial therapy. The development of novel diagnostic molecular marker(s) to detect circulating gastric cancer cells is an issue of great clinical importance. We obtained peripheral blood samples from 10 patients with gastric cancer who underwent laparotomy and 4 healthy volunteers. Microarray analysis consisting of 30,000 genes or ESTs was carried out using eight gastric cancer tissues and normal gastric mucosae. We selected 53 genes up-regulated in gastric cancer compared to normal gastric mucosae from our microarray data set, and, among these, identified five candidate marker genes (TSPAN8, EPCAM, MMP12, MMP7 and REG3A) which were not expressed in peripheral blood mononuclear cells (PBMCs) from 4 healthy volunteers. We further carried out semi-quantitative nested reverse transcription-polymerase chain reaction (RT-PCR) for HRH1, EGFR, CK20 and CEA in addition to the five newly identified genes using PBMCs of patients with gastric cancer, and found that expression of one or more genes out of the nine was detected in 80% of the patients with gastric cancer. Moreover, the numbers of genes expressed in PBMCs were ≤2 and ≥2 in all vascular invasion-negative cases and in 5 of 6 positive cases, respectively, showing significant differences between the two groups (P=0.041). Nested RT-PCR analysis for the set of nine marker genes using PBMCs may provide the potential for detection of circulating gastric cancer cells prior to metastasis formation in other organs.
PMCID: PMC3440735  PMID: 22977563
microarray; gastric cancer; molecular marker; nested RT-PCR; peripheral blood
20.  Malignant fibrous histiocytoma originating from the mesorectum: a case report 
Malignant fibrous histiocytoma (MFH) is a common sarcoma affecting soft tissues of the body, especially of the extremities or trunk. Prognosis of the abdominal MFH is usually poor.
Case presentation
A 52-year-old female presented to our surgical outpatient clinic with a lower abdominal tumor that had been gradually increasing in size. Clinical examination revealed a firm, irregularly surfaced, fixed, painless, child-head-sized tumor located in her lower abdomen. Computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen revealed a polycystic tumor at the lower abdomen which was 15 × 13 × 11 cm in diameter and encased the colorectum to the left back side. A barium enema and a colonoscopy showed direct invasion to the rectum. In 2001, the tumor had been excised along with a low anterior resection of the rectum because of direct invasion. The origin of this tumor was the mesorectum. The weight of the excised tumor was 1,500 g, including 800 ml of a brown fluid. A histopathological diagnosis revealed a common type of MFH, in which mitotic figures are frequently seen.
This patient has survived without recurrence, for approximately 8 years since the completed tumor resection. It is important to obtain a complete resection during the MFH treatment.
PMCID: PMC3038968  PMID: 21288322
21.  Rectal Carcinoma with Heterotopic Bone: Report of a Case 
Case Reports in Gastroenterology  2010;4(3):351-355.
Heterotopic bone is rarely present in malignant tumors of the gastrointestinal tract. We herein report a case of rectal adenocarcinoma with heterotopic bone. A 46-year-old Japanese male presented to our hospital with abdominal distension and constipation. Colonoscopic examination showed an ulcerated polypoid tumor of the rectum which nearly obstructed the rectal lumen. Abdominal computed tomography showed a tumor of the rectum with calcified deposits. Low anterior resection with lateral lymph node dissection was performed under the tentative diagnosis of rectal cancer. Histological examination of the resected specimen showed mucinous carcinoma of the rectum with heterotopic bone. One of the metastatic lymph nodes dissected also showed heterotopic bone. In the present report, we describe this rare tumor and briefly review the pertinent literature regarding rectal cancer with heterotopic bone.
PMCID: PMC2974998  PMID: 21060699
Rectum; Adenocarcinoma; Osseous metaplasia
22.  Clinical diagnostic criteria of autoimmune pancreatitis: revised proposal 
Journal of Gastroenterology  2006;41(7):626-631.
PMCID: PMC2780630  PMID: 16932998
autoimmune pancreatitis; diagnostic criteria; lymphoplasmacytic sclerosing cholangitis; IgG4
23.  Excision of a large abdominal wall lipoma improved bowel passage in a Proteus syndrome patient 
Proteus syndrome is an extremely rare congenital disorder that produces multifocal overgrowth of tissue. This report presents a surgical case of a large lipoma in the abdominal wall of a patient with Proteus syndrome. She was diagnosed with Proteus syndrome based on certain diagnostic criteria. The neoplasm increased in size gradually, producing hemihypertrophy of her left lower extremity and trunk, and spread to her retroperitoneum and her left abdominal wall. She experienced gradually progressive constipation, nausea, vomiting, and abdominal pain. Computed tomography (CT) of the abdomen demonstrated a large mass in the subcutaneous adipose tissue of the left lower abdominal wall which measured 12 cm × 8 cm x 6 cm in diameter and encased the left colon. This mass in the abdominal wall was excised. The weight of the excised mass was 1550 g. The histopathological diagnosis of this mass was lipoma. After surgery, the encasement of the left colon was improved, and the patient was able to move her bowels twice per day. The excision of the large lipoma in the abdominal wall contributed to the improved bowel passage in this patient with Proteus syndrome.
PMCID: PMC2710790  PMID: 19598310
Proteus syndrome; Lipoma; Bowel obstruction; Abdominal wall; Bowel passage
24.  Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer 
We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer.
We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg) of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks.
In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1), and another had general malaise (grade 1) and fever (grade 1). Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD). Immunologically, in 3 of the 10 patients (30%), an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%), although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols.
This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more effectively than vaccination with the peptide alone, although neither vaccination could induce efficient clinical responses. Considering the above, the addition of another effectual adjuvant such as a cytokine, heat shock protein, etc. to the vaccination with survivin-2B peptide mixed with IFA might induce improved immunological and clinical responses.
PMCID: PMC2430193  PMID: 18471305
25.  The Polyamine Spermine Rescues Arabidopsis from Salinity and Drought Stresses 
Plant Signaling & Behavior  2007;2(4):251-252.
There are accumulating reports that polyamines are involved in abiotic stress response. However, the role played by the polyamines is not fully elucidated. In the present studies, we assessed whether spermine among the polyamines plays a certain role against high salt and drought stresses using an Arabidopsis (acl5/spms) mutant plant that does not produce spermine, and found that it was hypersensitive to those stresses. In each case the hypersensitive phenotype was mitigated by application of exogenous spermine. The spermine-deficient mutant plants also showed a phenotype resembling Ca2+-deficiency. The NaCl-hypersensitivity and Ca2+-deficiency of acl5/spms double-knockout mutant resembled the phenotypes displayed by the AtGluR2- and CAX1-overexpressing transgenic plants. The two latter genes encode a glutamate receptor-type, Ca2+-ion influx channel at cytoplasmic membrane and a vacuolar Ca2+/H+ antiporter, respectively. The data suggest that regulated expression of the Ca2+-pathway members is critical to adapt to those stresses, and that spermine plays a certain role to control the stress-induced Ca2+ dynamics. Incorporating the current information from the literature, especially regarding action of polyamines on various ion channels, we present models describing a defensive role of spermine in high salt and drought stresses in Arabidopsis.
PMCID: PMC2634138  PMID: 19704669
Arabidopsis thaliana; calcium ion; drought stress; high salt stress; ion channels; polyamine; spermine

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