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Hiroyuki Konomi

Publications and source records attributed to Hiroyuki Konomi.

At least 19 recordsLinked to original sources
PubMed2006

S100A11, a putative tumor suppressor gene, is overexpressed in pancreatic carcinogenesis.

PURPOSE: Recent microarray analyses revealed that expression of S100A11 is up-regulated in pancreatic cancer. The aim of the present study was to evaluate the association of S100A11 with pancreatic carcinogenesis. EXPERIMENTAL DESIGN: We measured S100A11 mRNA expression in various clinical samples related to pancreatic cancer and its precursor lesions, intraductal papillary mucinous neoplasm (IPMN) and pancreatic intraepithelial neoplasia, by quantitative reverse transcription-PCR. RESULTS: Levels of S100A11 were significantly higher in pancreatic cancer (n=22) and IPMN (n=18) bulk tissues than in nonneoplastic bulk tissues (n=22; P<0.0001 for both). Levels of S100A11 did not differ between pancreatic cancer and IPMN bulk tissues. In microdissection analyses, however, IPMN cells (n=21) expressed significantly higher levels of S100A11 than did cancer cells (n=23; P=0.003). The median level of S100A11 expression was higher in pancreatic intraepithelial neoplasia cells (n=6) than in cancer cells. In pancreatic juice analyses, cancer-related (n=24; P=0.004) and IPMN-related (n=18; P=0.001) juice expressed significantly higher levels of S100A11 than did chronic pancreatitis-related juice (n=23). CONCLUSIONS: The present data suggest that expression of S100A11, a putative tumor suppressor gene, is increased in the early stage of pancreatic carcinogenesis and decreased during subsequent progression to cancer. Analysis of the S100A11 level in pancreatic juice may be an effective tool for screening of patients with high-risk lesions that could progress to pancreatic cancer or detecting early-stage pancreatic cancer.

Carcinoma↗
PubMed2006

S100P is an early developmental marker of pancreatic carcinogenesis.

PURPOSE: Our goal was to clarify the involvement and clinical significance of S100P in pancreatic carcinogenesis. EXPERIMENTAL DESIGN: We examined S100P expression in 45 bulk pancreatic tissues; in microdissected cells, including invasive ductal carcinoma (IDC) cells (20 sections), pancreatic intraepithelial neoplasia (PanIN) cells (12 sections), intraductal papillary mucinous neoplasm (IPMN) cells (19 sections), and normal epithelial cells (11 sections); and in pancreatic juice samples from 99 patients with pancreatic diseases (32 cancer, 35 IPMN, and 32 chronic pancreatitis samples). We used quantitative real-time reverse transcription-PCR with gene-specific priming to measure S100P in these various types of samples. RESULTS: In bulk tissue analyses, pancreatic cancer and IPMN expressed significantly higher levels of S100P than did nonneoplastic pancreas (P<0.017 and P=0.0013, respectively). Microdissection analyses revealed that IPMN expressed significantly higher levels of S100P than did IDC (P<0.0001) and PanIN (P=0.0031), although S100P expression did not differ between IDC and PanIN (P=0.077). In pancreatic juice analyses, cancer and IPMN juice expressed significantly higher levels of S100P than did pancreatitis juice (both P<0.0001). Receiver operating characteristic curve analyses revealed that measurement of S100P in pancreatic juice was useful for discriminating neoplastic disease from chronic pancreatitis (area under the curve=0.837; 95% confidence interval, 0.749-0.903). CONCLUSION: S100P may be an early developmental marker of pancreatic carcinogenesis, and measurement of S100P in pancreatic juice may be useful for early detection of pancreatic cancer or screening of early pancreatic carcinogenesis.

Adenocarcinoma, Mucinous↗
PubMed2006

Quantitative analysis of human telomerase reverse transcriptase in pancreatic cancer.

Although telomerase activity is a promising diagnostic marker, clinical introduction of this marker for cancer diagnosis is still problematic due to the lack of means of evaluating sample quality. Human telomerase reverse transcriptase (hTERT), one of the subunits of telomerase, is also a promising diagnostic marker. In the present study, we did large-scale analysis of 88 pancreatic juice samples to determine the feasibility of quantitative analysis of hTERT mRNA for diagnosis of pancreatic cancer. We found significant differences in hTERT expression among carcinoma-derived, intraductal papillary mucinous neoplasm (IPMN)-derived, and chronic pancreatitis-derived juice samples. Results showed that quantitative analyses of hTERT mRNAs are more useful in discriminating carcinoma from IPMN than from chronic pancreatitis. When the specificity was set at 100%, the sensitivity for differentiation between carcinoma and IPMN was 43.5%, whereas the sensitivity of cytologic examination was 22.0%. There were significant differences in hTERT expression among carcinoma cells, IPMN cells, and normal ductal cells isolated from pancreatic tissues by microdissection. Lymphocytes and hyperplastic epithelial cells isolated from tissues with the histologic appearance of pancreatitis showed various expression levels of hTERT. Our results suggest that quantitative analysis of hTERT mRNA in pancreatic juice is advantageous over cytologic analysis for differentiation between carcinoma and IPMN but probably not for differentiation between carcinoma and chronic pancreatitis.

DNA-Binding Proteins↗
PubMed2006

Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer.

Pancreatic juice is a promising type of diagnostic sample for pancreatic cancer, and members of the mucin (MUC) family are diagnostic candidates. To evaluate the utility of MUC family members as diagnostic markers, we measured MUC mRNA expression in pancreatic tissues and pancreatic juice obtained from patients with different pancreatic diseases as well as in pancreatic cancer cell lines by real-time PCR. Furthermore, to support the possibility of early diagnosis by quantification of MUC1 and MUC5AC, immunohistochemistry and microdissection-based quantitative analysis of mRNA were carried out. There was no significant correlation between MUC1 and MUC5AC expression in cell lines. When beta-actin was used as a reference gene, median MUC1 and MUC5AC mRNA expression levels were remarkably greater in tumoral tissues than in non-tumoral tissues, but median MUC4 and MUC6 mRNA expression levels were not. Receiver operating characteristic curve analysis showed that quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice is better diagnostic modality than that of MUC4 and MUC6 mRNA. Immunohistochemistry showed that MUC1 and MUC5AC were highly expressed in invasive ductal carcinomas (IDC) and moderately expressed in high-grade pancreatic intraepithelial neoplasia (PanIN); no staining was observed in normal ducts. Analysis of cells isolated by microdissection showed stepwise upregulation of MUC1 and MUC5AC in the development of high-grade PanIN to IDC. Our results suggest that MUC1 and MUC5AC are upregulated stepwise in pancreatic carcinogenesis and that quantitative assessment of MUC1 and MUC5AC mRNA in pancreatic juice has high potential for preoperative diagnosis of pancreatic cancer.

Biomarkers, Tumor↗
PubMed2006

Long-term results of treatment for pancreaticobiliary maljunction without bile duct dilatation.

HYPOTHESIS: Resection of the gallbladder together with the dilated bile duct is the preferred treatment for pancreaticobiliary maljunction (PBM) with bile duct dilatation, whereas this treatment for PBM without bile duct dilatation is still controversial. DESIGN: Retrospective study of 196 patients from January 1979 to November 2004. SETTING: Two university hospitals. PATIENTS: One hundred ninety-six patients with PBM, 152 (78%) with and 44 (22%) without bile duct dilatation, formed the basis of this study. MAIN OUTCOME MEASURES: The effects of cholecystectomy on long-term results in the patients without bile duct dilatation. RESULTS: Significant differences were observed in patients without bile duct dilatation: patients were older, carcinoma of the gallbladder was more prevalent (19 patients [43.2%] without dilatation vs 9 patients [5.9%] with dilatation), and pancreatic cancer and pancreatitis were also more frequent. Most of their gallbladder carcinomas were found at stage IV (63%). The outcome was very poor in stage IV, whereas 5 patients in stage I and II lived for more than 5 years after surgery. Of the 44 patients without bile duct dilatation, 23 with carcinoma of the gallbladder or pancreas died and the other 2 were lost to follow-up. The remaining 19 patients were alive at the study's conclusion after cholecystectomy without bile duct resection. None of them had bile duct carcinoma at the time of surgery or during the mean follow-up period of 9 years after surgery. CONCLUSIONS: Prophylactic cholecystectomy without bile duct resection is the best treatment option for patients with PBM without bile duct dilatation. Possible association of gallbladder carcinoma should be kept in mind at the time of treatment of patients with PBM when the bile duct is not dilated.

Adolescent↗
PubMed2006

Type of gastrointestinal reconstruction affects postoperative recovery after pancreatic head resection.

BACKGROUND/PURPOSE: The postoperative recovery of gastric motility with various reconstructions after pancreatic head resection has been reported. However, little is known about this recovery after pancreatic head resection with segmental duodenectomy (PHRSD). Some have attributed gastric stasis after pylorus-preserving pancreatoduodenectomy (PPPD) to tube gastrostomy, but its effect on gastric motility has not been investigated. In this study, the postoperative recovery after PHRSD and PPPD, and gastric motility with and without gastrostomy after PPPD were investigated. METHODS: We analyzed the first appearance of gastric phase III motility, postoperative systemic status, and body weight (BW; n = 32). The Imanaga PPPD and PHRSD were compared because the procedures differ only in the length of the remaining duodenum. Traverso and Roux-en-Y PPPDs were compared because the two procedures are similar except for the creation of gastrostomy. RESULTS: (1) Times to first appearance of gastric phase III motility and BW recovery were significantly better after PHRSD than after the Imanaga PPPD (P < 0.05). (2) Times to first gastric phase III motility and resumption of a regular diet as well as periods of gastric sump tube use and postoperative hospital stay were significantly shorter after the Roux-en-Y than after the Traverso PPPD (P < 0.05). CONCLUSIONS: Preservation of as long a portion of the duodenum as possible, the choice of a Roux-en-Y duodenojejunostomy, and the avoidance of peritoneal fixation of the gastric wall may be factors that improve the recovery of gastric motility and BW after pancreatic head resection.

Adult↗
PubMed2006

[A case of primary gastric malignant lymphoma perforated immediately after administration of chemotherapy].

A 77-year-old man was admitted to our hospital with complaints of abdominal pain and body weight loss. Esophagogastroduodenoscopy on admission revealed large ulcerative tumor in the entire region from upper to lower body of the stomach. We diagnosed gastric malignant lymphoma, diffuse large B-cell type and determined stage IV according to the Lugano International Conference classification. Due to gastric perforation occurred on day 4 of chemotherapy, total gastrectomy and partial resection of the transverse colon were performed. Complete remission was achieved by 2 cycles of postoperative chemotherapy together with rituximab.

Aged↗
PubMed2005

The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target.

Recent microarray analyses showed that the S100 family contains members that are candidate diagnostic markers or therapeutic targets. In the present study, to evaluate the involvement of S100A6 in pancreatic cancer and its clinical usefulness for diagnosis, we examined S100A6 mRNA expression in pancreatic tissues and pancreatic juice from patients with different pancreatic diseases. To investigate the role of S100A6 in carcinogenesis of pancreatic cancer and the potential of S100A6 as a diagnostic marker for early detection of pancreatic cancer, we did immunohistochemistry and microdissection-based mRNA analysis of pancreatic normal ducts, pancreatic intraepithelial neoplasias, and invasive ductal carcinomas. We also used in vitro experiments and microarray analysis with RNA interference to evaluate the functional role of S100A6 and its potential as a therapeutic target for pancreatic cancer. S100A6 mRNA levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. In pancreatic juice, there was a significant difference in S100A6 expression between patients with carcinoma and those with nonneoplastic disease. Receiver operating characteristic curves revealed that S100A6 might be a useful marker for diagnosis of pancreatic cancer. Immunohistochemistry and microdissection-based analysis showed differential expression of S100A6 among normal ducts, pancreatic intraepithelial neoplasias, and invasive ductal carcinomas. In vitro data showed that inhibition of S100A6 decreased proliferation and invasiveness of cancer cells, and these findings were supported by microarray data. Our present results suggest that quantitation of S100A6 mRNA is a promising tool for diagnosis of pancreatic cancer, and that S100A6 may be a promising therapeutic target for pancreatic cancer.

Biomarkers, Tumor↗
PubMed2005

Pancreatic juice cytology in IPMN of the pancreas.

BACKGROUND: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a disease ranging from adenoma to borderline (with moderate dysplasia) and further to carcinoma (noninvasive and invasive) and surgical strategy is different by the grades of dysplasia. METHODS: Preoperative pancreatic juice cytology in IPMN was reviewed in 71 patients with IPMN who underwent surgical resection. RESULTS: The IPMN was adenoma in 48 patients, borderline in 13 and carcinoma (invasive) in 10. The sensitivity of pancreatic juice cytology in malignant IPMN was 40% (4/10). In 4 patients with the 48 IPM adenomas, diagnosis of pancreatic juice cytology was class IV or V. One of the 4 cases was considered to be an overdiagnosis of cytology, but the other 3 cases were considered to be a consequence of accompanying carcinoma in situ (or PanIN-3) (2 patients) or invasive ductal adenocarcinoma (1 patient) apart from IPMN. Sensitivity of pancreatic juice cytology was higher in IPMN of the main duct type with mucin hypersecretion and with mural nodules. CONCLUSIONS: These findings suggest that pancreatic juice cytology in IPMN is useful especially in the main duct type with mucin hypersecretion and mural nodules. When the diagnosis of pancreatic juice cytology is malignant in otherwise benign-looking IPMNs, coexistence of pancreatic carcinoma should be suspected.

Adenocarcinoma, Mucinous↗
PubMed2005

A minute nonfunctioning islet cell tumor demonstrating malignant features.

We report a patient with a minute nonfunctioning islet cell tumor, 8 mm in diameter, which demonstrated malignant features by histology. The patient was a 43-year-old Japanese woman, who had an elevated carbohydrate antigen (CA) 19-9 level, of 59 U/ml (normal range, <37 U/ml) identified on a health check to rule out malignancies. Ultrasonography and computed tomography demonstrated a well-defined pancreatic tumor, 8 mm in diameter, in the body of the pancreas. Serum levels of pancreatic hormones were within normal limits, and thus a tentative diagnosis was nonfunctioning islet cell tumor. The size of the tumor remained unchanged for 1 1/2 years, but, at this time, the serum level of CA19-9 was elevated to 253 U/ml. Segmental pancreatectomy was performed because malignancy could not be ruled out. The resected specimen showed an endocrine tumor invading both the pancreatic parenchyma and the perineural spaces outside the tumor. In general, minute nonfunctioning islet cell tumors have been considered to be completely benign, but the present tumor showed clear malignant features. We might have to take surgical resection into consideration even if the size of such an endocrine tumor is minute.

Adenoma, Islet Cell↗
PubMed2005

Duodenum is important for the sphincter of Oddi motor response to cholecystokinin octapeptide in conscious dogs.

BACKGROUND: We investigated the role of the duodenum in the sphincter of Oddi response to cholecystokinin-octapeptide (CCK-OP), using conscious dogs. METHODS: In controls, a cannula was inserted into the duodenum opposite the papilla for retrograde manometry. In the duodenectomy group, the entire duodenum was resected, while preserving the papilla, which was implanted into the jejunum, and the cannula was placed. Sphincter motility was recorded after bolus injections of 20 and 100 ng/kg of CCK-OP. RESULTS: CCK-OP at 20 ng/kg produced sphincter relaxation followed by contraction in the controls, but produced no changes after duodenectomy. CCK-OP at 100 ng/kg caused strong contractions followed by relaxation in the controls, but caused only contractions after duodenectomy. CONCLUSIONS: (1) Relaxation and delayed contraction of the sphincter induced by 20 ng/kg of CCK-OP require the presence of the duodenum; (2) early contractions of the sphincter induced by 100 ng/kg of CCK-OP do not require the duodenum; (3) the duodenum plays an important role in the actions of CCK-OP on sphincter motility.

Animals↗
PubMed2005

[Recent advances in diagnosis of pancreatic cancer].

The clinical course of patients with pancreatic cancer remains dismal. This may be because the pancreas is a retroperitoneal organ, the symptoms are non-specific, occur late, and pancreas cancer has an invasive nature. Screening for asymptomatic or symptomatic patients using serum tumor markers and ultrasonography is not cost-effective. However, the clinical course of small carcinomas less than 1 cm or 1 cm in size is favorable. Thus, the detection of small pancreatic carcinoma is essential to improve the clinical outcome. Possible discovery of pancreatic carcinoma as a diagnostic clue to diabetes mellitus, and intraductal papillary-mucinous neoplasm are introduced based on our clinical experience.

Adenocarcinoma, Mucinous↗
PubMed2004

Spleen-preserving laparoscopic distal pancreatectomy after division of the splenic vessels.

A 37-year-old woman with a history of syncope was hospitalized with a diagnosis of hypoglycemia due to insulinoma. Computed tomography (CT) and magnetic resonance imaging revealed an enhanced solid mass, 1.5 cm in diameter, at the tail of the pancreas. Angiography via the splenic artery revealed a hypervascular mass. Because the tumor was located deep in the pancreatic parenchyma, laparoscopic distal pancreatectomy was performed. The pancreas was exposed by dissecting the greater omentum, and the tumor was located by intraoperative ultrasonography. After division of the splenic artery, the pancreas, main pancreatic duct, and splenic vein were transected with an endoscopic linear stapler. The pancreatic pedicle was divided at the splenic hilum to preserve the spleen. The postoperative course was uneventful except for the appearance of splenic infarction on a CT scan 2 weeks after surgery but without any overt symptoms. Spleen-preserving laparoscopic distal pancreatectomy by division of splenic vessels is a feasible treatment option for benign pancreatic disease.

Adult↗
PubMed2004

Second-generation recombinant hemoglobin molecules do not stimulate sphincter of Oddi, gallbladder or duodenal motility in the Australian brush-tailed possum.

BACKGROUND: Several studies have investigated the effects of hemoglobin-based oxygen carriers on gastrointestinal motility. Diaspirin cross-linked hemoglobin reduces sphincter of Oddi trans-sphincteric flow and increases duodenal motility in the Australian brush-tailed possum, effects attributed to nitric oxide (NO) scavenging. Recently, second-generation recombinant hemoglobin molecules with reduced NO scavenging ability have been developed. AIM: To determine the effects of two second-generation recombinant hemoglobin solutions and the prototype recombinant hemoglobin with high NO binding, on duodenal and biliary motility in the Australian brush-tailed possum. METHOD: Blood pressure; duodenal, sphincter of Oddi and gallbladder motility; and trans-sphincteric flow were recorded. The effects of recombinant hemoglobin or human serum albumin (control) solutions on these parameters were investigated. Each solution was infused intravenously at 1 mL/kg/min to deliver 250 mg/kg or 500 mg/kg. RESULTS: Duodenal contraction frequency was stimulated by the high dose of prototype recombinant hemoglobin, but not by a comparable dose of second-generation recombinant hemoglobin. The induced duodenal activity occurred in the later phase of the experimental period. In contrast, biliary motility and trans-sphincteric flow were not altered by any hemoglobin solution. The high dose of all the hemoglobin solutions elevated blood pressure, whereas the low dose solutions did not alter any parameter measured. CONCLUSION: At the doses studied, the second-generation recombinant hemoglobin with reduced NO binding capacity did not significantly alter duodenal and biliary motility, supporting the need for further studies to evaluate their potential usefulness as blood substitutes.

Animals↗
PubMed2003

Appleby operation for pancreatic body-tail carcinoma: report of three cases.

The clinical course of patients with carcinoma of the pancreas, especially of the body-tail, remains dismal despite recent advances in diagnostic and therapeutic procedures. We present three case reports to evaluate the role of the Appleby operation in the treatment of pancreatic body-tail cancer. Care 1 was a 55-year-old Japanese woman who underwent the Appleby operation for mucinous cystadenocarcinoma of the body and tail of the pancreas invading the stomach, celiac axis, superior mesenteric and splenic arteries, and the splenic, superior mesenteric, and portal veins. Local recurrence and peritoneal dissemination with malignant ascites were found 7 months later and she died 10 months after the operation. Case 2 was a 61-year-old Japanese man who underwent the Appleby operation with 20 Gy radiation therapy for invasive ductal carcinoma of the body of the pancreas involving the celiac axis, common hepatic, splenic, and left gastric arteries, and the splenic vein. Peritoneal dissemination with malignant ascites was evident 5 months later and he died 14 months after the operation. Case 3 was a 50-year-old Japanese man who underwent the Appleby operation with 20 Gy radiation therapy for invasive ductal carcinoma of the body of the pancreas invading the stomach, splenic artery, celiac axis, and splenic vein. Multiple hepatic metastases were found 2 months later and the patient died 8 months after the operation. Based on our experience of these three cases, we conclude that the indications for the Appleby operation to treat locally advanced pancreatic body carcinoma are still limited because it does not improve quality of life or clinical outcome.

Biopsy, Needle↗