Biomedical subjects

Koji Oda

Publications and source records attributed to Koji Oda.

At least 19 recordsLinked to original sources

PubMed2005

TNM classification for perihilar cholangiocarcinoma: comparison between 5th and 6th editions of the AJCC/UICC staging system.

BACKGROUND: A few investigators have evaluated the TNM classification for perihilar cholangiocarcinoma. The new sixth edition of the American Joint Committee on Cancer (AJCC)/Internal Union Against Cancer (UICC) staging system focuses on vascular invasion and regional lymph node metastasis. METHODS: For 166 patients with perihilar cholangiocarcinoma undergoing R0 resection, survival curves stratified according to TNM classifications were compared between fifth and sixth editions. RESULTS: The previous T3 now is divided into T3 and T4. Most new pT4 patients had invasion of the portal bifurcation; their survival was poorer than that for new pT3 patients. The 5-, 10-, and 15-year survival rates were worse in the previous stage III than in the previous stage IVA, although the difference fell short of significance. The previous stage IVA (T3 Any NM0) is divided into new stages: IIA (T3N0M0), IIB (T1-3N1M0), and III (T4 Any NM0). All patients in stage III had invasion of the portal bifurcation. Survival was similar between stages IA, IB, and IIA, while patients with T4N0M0 tumors survived longer than those with T4N1M0 tumors and similarly to those with stage IIB tumors. CONCLUSIONS: The sixth edition provided improved prediction of survival in patients with perihilar cholangiocarcinoma; for still better prediction, cancer invasion of the portal bifurcation and regional lymph node metastasis should be weighted equally.

Adult↗

PubMed2005

Impaired expression of hepatic multidrug resistance protein 2 is associated with posthepatectomy hyperbilirubinemia in patients with biliary cancer.

BACKGROUND AND AIMS: Hyperbilirubinemia is a critical complication following hepatectomy for biliary cancer. Hepatic multidrug resistance protein 2 (MRP2), a bilirubin transporter, is shown to be down-regulated by acute biliary obstruction in rats. However, little is known about the effect of chronic obstruction by malignancy on the MRP2 expression in patients or the association of MRP2 expression with posthepatectomy hyperbilirubinemia. MATERIALS AND METHODS: The MRP2 expression before hepatectomy was determined by immunostaining and Western blotting in patients with biliary cancer. To directly determine the effect of chronic bile duct obstruction on the MRP2 expression, the expression levels were compared between the cholestatic and noncholestatic lobes in each of seven patients. In another 39 patients, the correlation of the MRP2 expression of the anticipated remnant liver with the posthepatectomy severe hyperbilirubinemia, defined as a serum total bilirubin concentration>or=200 micromol/l, was evaluated. RESULTS: The MRP2 staining in the cholestatic lobes was weak and not restricted to the canalicular membrane, unlike the noncholestatic lobes. The expression levels in the cholestatic lobes were 45% of those in the noncholestatic lobes. Postoperative maximum bilirubin levels were significantly correlated with MRP2 expression of the anticipated remnant liver. The MRP2 expression had been already impaired before hepatectomy in all patients who eventually developed severe hyperbilirubinemia. CONCLUSIONS: Decreased MRP2 expression, caused by biliary obstruction due to cancer, is a possible risk factor for posthepatectomy severe hyperbilirubinemia.

Adult↗

PubMed2005

Tumor necrosis factor alpha promotes invasiveness of cholangiocarcinoma cells via its receptor, TNFR2.

We studied the effect of TNF-alpha stimulation on a cholangiocarcinoma cell line, CCKS1. CCKS1 expressed only one type TNF receptor, TNFR2. Treatment of CCKS1 with TNF-alpha substantially activated NFkappaB, MAPK and Akt signalings which in turn activated matrix metalloproteinase-9 (MMP-9) secretion and in vitro invasiveness of CCKS1. Pretreatment of cells with anti-TNFR2 neutralizing antibody inhibited the TNF-alpha-dependent signaling and MMP-9 secretion and subsequently blocked invasion in vitro. Moreover, an inhibitor for matrix metalloproteinase, Galardin, suppressed the invasion in a dose-dependent manner. Similarly, pharmacological inhibition of signaling clearly suppressed the TNF-alpha dependent MMP-9 secretion. These results strongly suggest that TNF-alpha-TNFR2 signaling plays an important role to convert the cholangiocarcinoma cells to be more aggressive one.

Cholangiocarcinoma↗

PubMed2005

Intense PET signal in the degenerative necrosis superimposed on chronic pancreatitis.

Although fluorine-18 deoxyglucose-positron emission tomography (FDG-PET) is a sensitive diagnostic modality in detecting malignant tumors, differential diagnosis of malignant tumors from inflammatory lesion is challenging. We experienced a case of acute degenerative necrosis superimposed on chronic pancreatitis, which was difficult to distinguish from pancreatic cancer. The patient was a 66-year-old man with a complaint of upper abdominal pain. Abdominal computed tomography revealed low-density masses in the head and body of the pancreas. FDG-PET revealed intense accumulations at the head and body of the pancreas (mean standard uptake value for the head and body pancreatic tumors was 4.1 and 6.7, respectively) corresponding to the 2 tumors detected by computed tomography. Because of a possible malignant pancreatic tumor, the patient underwent pylorus-preserving pancreatoduodenectomy. Histologic examination of the resected specimen revealed a characteristic of chronic pancreatitis in a nontumorous area. Two tumors detected by FDG-PET consisted of degenerative necrosis surrounded by granulation tissue. The amount of granulation tissue was correlated to the levels of standard uptake value. No malignant tumors were observed. This case suggests a limitation of FDG-PET in distinguishing malignant neoplastic lesions in the pancreas, especially from acute degenerative changes in chronic pancreatitis. Repetitive PET examination is recommended for the accurate diagnosis.

Aged↗

PubMed2005

Aberrant expression of pyloric gland-type mucin in mucin-producing bile duct carcinomas: a clear difference between the core peptide and the carbohydrate moiety.

The authors have recently defined the clinopathological entity of a mucin-producing bile duct tumor (MPBT), and divided MPBT into two distinct subtypes: 'columnar-type' and 'cuboidal-type' MPBT. Mucin core protein 6 (MUC6), which is present in normal pyloric glands, had higher expression levels in cuboidal-type tumors than in columnar-type tumors. In the pyloric glands, a carbohydrate antigen detected by monoclonal antibody HIK1083 (CA/HIK1083) is also expressed. In order to evaluate the coexpression pattern of MUC6 and CA/HIK1083 in MPBT, expression profiles were evaluated in 38 surgically excised mucin-producing bile duct carcinomas (MPBC; cuboidal-type, n = 15; columnar-type, n = 23), using immunohistochemistry. The staining rate was graded as follows: -, <5% of neoplastic cells stained; +, 5% to <20%; + +, 20% to <50%; + + +, > or =50%. In cuboidal-type MPBC, MUC6 was positive in all cases (+ + +, 13/15; + +, 1/15; +, 1/15), whereas CA/HIK1083 was negative in all cases (-, 15/15; P < 0.0001). In columnar-type MPBC, MUC6 was positive in 65% of cases (+ + +, 6/23; + +, 8/23; +, 1/23; -, 8/23), and CA/HIK1083 was positive in 52% (+ +, 3/23; +, 9/23; -, 11/23; not significant). Our results clearly demonstrate that cuboidal-type MPBC have an aberrant pyloric glandular phenotype, that is, MUC6+/CA/HIK1083-. This unique profile may be related to different outcomes of patients with MPBC.

Adenocarcinoma, Mucinous↗

PubMed2004

Prognostic significance of the location of intramural metastasis in patients with esophageal squamous cell carcinoma.

BACKGROUND: Although the presence of an intramural metastasis (IM) from esophageal cancer is associated with a poor prognosis, some patients with IM have a relatively favorable course. METHODS: Clinicopathological factors including number, location, and size of IM and the distance between the primary tumor and IM were assessed in 212 patients with esophageal squamous cell carcinoma who underwent esophagectomy. RESULTS: Twenty-three patients (10.8%) had IM. IM size ranged from 2 to 100 mm (18+/-26), and the distance between primary lesion and IM ranged from 5 to 70 mm (27+/-18). Survival of ten patients with an IM less than 20 mm from the primary tumor was significantly longer than that of 13 patients with a more distant IM ( P=0.0184); median survival time were 2.3 and 0.7 years, respectively. CONCLUSION: A subgroup of patients with an IM less than 20 mm from the primary esophageal cancer may have a relatively favorable prognosis. When an IM is found preoperatively or in a resected specimen, measurement of the distance between the primary tumor and the IM might be useful in determination of treatment strategy and evaluation of prognosis.

Adult↗

PubMed2004

Genipin enhances Mrp2 (Abcc2)-mediated bile formation and organic anion transport in rat liver.

Inchin-ko-to (ICKT), an herbal medicine, and its ingredients exert potent choleretic effects by a "bile acid-independent" mechanism. The current study was designed to determine whether ICKT or its ingredients potentiate multidrug resistance-associated protein 2 (Mrp2; Abcc2)-mediated choleresis in vivo. Biliary secretion of Mrp2 substrates and the protein mass, subcellular localization, and messenger RNA (mRNA) level of Mrp2 were assessed in rat liver after infusion of genipin, an intestinal bacterial metabolite of geniposide, a major ingredient of ICKT. The function of Mrp2 was also assessed by the adenosine triphosphate (ATP)-dependent uptake of Mrp2-specific substrates using canalicular membrane vesicles (CMVs) from the liver. Infusion of genipin increased bile flow by 230%. It also increased biliary secretion of bilirubin conjugates and reduced glutathione (GSH) by 513% and 336%, respectively, but did not increase bile acid secretion. The ATP-dependent uptake of estradiol 17-beta-D-glucuronide (E(2)17 beta G; by 265%), leukotriene C4 (LTC(4); by 161%), taurolithocholate-3-sulfate (TLC-3S; by 266%), and methotrexate (MTX; by 234%) was significantly stimulated in the CMVs from the liver. These effects were not observed in Mrp2-deficient rats. Under these conditions, genipin treatment increased the protein mass of Mrp2 in the CMVs but not the mRNA level. In immunoelectron microscopic studies, a marked increase in Mrp2 density in the canalicular membrane (CM) and microvilli was observed in the genipin-treated liver tissue sections when compared with the vehicle-treated liver tissue sections. In conclusion, genipin may enhance the bile acid-independent secretory capacity of hepatocytes, mainly by stimulation of exocytosis and insertion of Mrp2 in the bile canaliculi. ICKT may be a potent therapeutic agent for a number of cholestatic liver diseases.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Epidermoid cyst in an intrapancreatic accessory spleen: a case report.

Ectopic splenic tissue in the abdominal cavity is a common entity, with a reported incidence of 10% in the general population. However, an intrapancreatic accessory spleen is a rare disease, and moreover cyst formation in it is exceedingly rare. A 58-year-old woman with a 25-mm multilocular cyst in the tail of the pancreas detected incidentally by ultrasonography was admitted for further evaluation. Because malignancy could not be ruled out, a spleen-preserving distal pancreatectomy was performed. The cut surface of the surgical specimen showed a multilocular cyst surrounded by brown solid tissue resembling normal spleen. Pathological examination revealed it was stratified squamous epithelium and was surrounded by splenic tissue. The final pathological diagnosis was epidermoid cyst in an accessory spleen in the pancreas. This cyst has no characteristic features on diagnostic imaging. Consequently, it is not possible to make a definite preoperative diagnosis in most cases. Epidermoid cyst in intrapancreatic splenic tissue is another lesion to be considered in the differential diagnosis of pancreatic tail tumors.

Endosonography↗

PubMed2004

Complete resection of hepatocellular carcinoma with direct invasion to the stomach remnant.

A 61-year-old man presented with anemia (hemoglobin, 5.9 mg/dl) and a history of alcoholic liver disease. The patient also had a past history of a distal gastrectomy and Billroth II reconstruction, due to a gastric ulcer, performed 20 years previously. Endoscopic gastroscopy revealed a hemorrhagic ulcerative tumor at the gastrojejunostomy site. Computed tomography and angiography demonstrated a 10-cm tumor and a 2-cm tumor in the left lateral segment of the liver, suggestive of hepatocellular carcinoma (HCC). The larger tumor showed extrahepatic growth, with invasion of the stomach remnant. Because transcatheter arterial embolization of the tumor failed to control the bleeding, we carried out an en-bloc resection of the left lateral segment of the liver and the stomach remnant. Direct invasion of HCC into the gastrointestinal tract is rarely encountered. Here we report a case of HCC that invaded the stomach remnant and present a review of the literature.

Carcinoma, Hepatocellular↗

PubMed2004

Mutations identified in the human multidrug resistance P-glycoprotein 3 (ABCB4) gene in patients with primary hepatolithiasis.

Primary hepatolithiasis (HL), highly prevalent in the Far East, including Japan, is characterized clinically by chronic proliferative cholangitis with frequent recurrences. In HL patients, hepatic hyposecretion of phospholipid due to decreased multidrug resistance P-glycoprotein 3 (MDR3; now referred to as ABCB4) expression levels (Hepatology 2001;33:1194-1205) may contribute to the formation of aggressive ductular lesions through a decreased formation of mixed micelles. However, specified factors underlying the decreased expression levels of MDR3 have not been well defined. To determine whether the decreased MDR3 expression level is associated with the gene mutations, mutation analysis of cDNA of the MDR3 gene with focus on the coding region was performed using liver specimens. Heterozygous mutations were detected in only two of 16 HL patients. By sequence analysis of the gene, a 77-bp deletion at nucleotides 537-613 in exon 7 in transmembrane domain (TM) 3, which results in a frameshift at codon 179 and an early stop codon predicting a truncated protein, was found as a heterozygous mutation in two of the 16 patients. A 1-bp deletion at nucleotide 1015 in exon 10 in TM 6 was found as a heterozygous mutation in one of those two patients, and a 242-bp deletion at nucleotides 2683-2924 in exons 22-23 in TM 11 was found as a heterozygous mutation in the same patient. No other mutations were found in the other 14 patients. In real-time polymerase chain reaction (PCR), no significant difference was found between the mRNA levels of MDR3 in the two HL patients with mutations nor in the other 14 patients without mutations. Immunostaining of MDR3 protein was found in the bile canaliculi of liver sections from the two patients with mutations. The results suggest that in primary HL the decreased transcription levels of MDR3 in the liver are not due to the mutations detected in the coding region of the gene.

Journal Article↗

PubMed2004

Frequent p16ink4a inactivation is an early and frequent event of intraductal papillary neoplasm of the liver arising in hepatolithiasis.

Intraductal papillary neoplasm of the liver (IPNL) is a precursor lesion of intrahepatic cholangiocarcinoma (ICC) arising in hepatolithiasis. In this study, 98 foci of IPNL identified in 39 surgically resected hepatolithiatic livers were investigated for expression of p16INK4a, cyclin D1, p21WAF1/CIP1, p53, mouse double-minute 2 (MDM2), and pRb. In addition, methylation-specific polymerase chain reaction (MSP) for p16 INK4a promoter region was performed in these foci. Nonneoplastic bile ducts from 11 hepatolithiatic livers, 5 histologically normal livers, and 9 cases of nonpapillary conventional ICC were used as controls. Decreased expression of p16INK4A was seen in IPNL group 1 with mild dysplasia and continued along the progression of IPNL to ICC. The expression of cyclin D1, p21WAF1/CIP1,and pRb gradually increased along the progression of IPNL to ICC and became significantly high in IPNL of group 3 (carcinoma in situ). The expression of p53 and MDM2 was increased in IPNL group 3 and group 4 with evident invasive carcinoma. MSP revealed that 54.6% of 44 IPNL foci harbored p16INK4a promoter hypermethylation, and such foci were significantly correlated with decreased expression of p16INK4a protein. Ki-67 labeling index exhibited a stepwise increase from IPNL group 1 to group 4. We conclude that p16INK4a inactivation, due mainly to its promoter hypermethylation, is a frequent and early event of IPNL and may be responsible for genetic and epigenetic alterations of other cell cycle regulators in IPNL.

Adenoma, Bile Duct↗

PubMed2004

Aberrant expression of CDX2 is closely related to the intestinal metaplasia and MUC2 expression in intraductal papillary neoplasm of the liver in hepatolithiasis.

Intraductal papillary neoplasia of the liver (IPNL) frequently presents gastrointestinal metaplasia with aberrant expression of MUC2 and MUC5AC and oversecretion of mucin into the ductal lumen. In this study, the involvement of CDX2, a homeodomain protein involved in the regulation of intestinal development and differentiation, in the expression of MUC2 was examined in mucinous intrahepatic cholangiocarcinoma (ICC) (n=7) and IPNL with hepatolithiasis (n=19) with comparison to conventional ICC (n=11), and intraductal papillary mucinous tumor and invasive ductal carcinoma of the pancreas (n=9 and 11, respectively). A total of 33 cases of hepatolithiasis, extrahepatic biliary obstruction and normal livers were used as the control. Immunohistochemically, both MUC2 and MUC5AC were frequently expressed in mucinous ICC and IPNL, while expression of MUC2 was not seen in conventional ICC. The nuclear expression of CDX2 was closely associated with the expression of MUC2 in mucinous ICC and IPNL. This intimate association of MUC2 and CDX2 was confirmed by double immunostaining. The cytoplasmic CDX2 expression was frequent in the mucinous and the conventional ICC and pancreatic carcinoma, irrespective of MUC2 and MUC5AC expression. CDX2 mRNA was detected in neoplastic cells showing cytoplasmic as well as nuclear expression of CDX2 by reverse transcriptase-polymerase chain reaction. One IPMT expressed MUC2 associated with nuclear CDX2 expression, while the other IPMT and conventional pancreatic carcinoma expressed MUC5AC only. Aberrant expression of CDX2 is closely related to the overexpression of MUC2 in mucinous ICC and IPNL associated with hepatolithiasia, suggesting its role in intestinal differentiation and its association with carcinogenesis in these tumors.

Adult↗

PubMed2004

Pathologic features of mucin-producing bile duct tumors: two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms.

Tumors with clinically recognizable mucin production arising from bile duct, "mucin-producing bile duct tumors (MPBTs)," have not been studied yet for their pathologic features and classification in details. The clinical findings of MPBT have a lot of similarities to those of pancreatic intraductal papillary-mucinous neoplasm. In the present study, we examined 30 MPBTs and classified them into two distinct morphologic categories: 22 cases of "columnar type" composed of pseudostratified columnar cells with basophilic cytoplasm and columnar nuclei and 8 cases of "cuboidal type" composed of pancreaticobiliary and/or oncocytic pattern. Pancreaticobiliary pattern showed abundantly branched papillae lined by acidophilic cuboidal cells with round nuclei, whereas oncocytic pattern was characterized by intraepithelial lumina and cribriform pattern composed of abundant oxyphilic cells with round nuclei, and these patterns overlapped frequently. There were significant differences in the clinicopathologic findings including macroscopic findings, morphometric data, mucin expression profiles (MUC2 expression in columnar type and MUC6 expression in cuboidal type), and cell proliferative activities between columnar type and cuboidal type. Patients with columnar type showed significantly poorer survival than those with cuboidal type. We concluded that columnar type and cuboidal type of MBPTs belong to different lineage of neoplasm and that they are counterparts of "intestinal type" and "pancreaticobiliary type" of pancreatic intraductal papillary-mucinous neoplasm, respectively.

Adenocarcinoma, Papillary↗

PubMed2004

Surgical anatomy of the bile ducts at the hepatic hilum as applied to living donor liver transplantation.

OBJECTIVE: To evaluate anatomic variations of the biliary tree as applied to living donor liver transplantation. SUMMARY BACKGROUND DATA: Anatomic variability is the rule rather than the exception in liver surgery. However, few studies have focused on the anatomic variations of the biliary tree in living donor liver transplantation in relation to biliary reconstruction. METHODS: From November 1992 to June 2002, 165 patients underwent major hepatectomy with extrahepatic bile duct resection; right-sided hepatectomy in 110 patients and left-sided hepatectomy in 55. Confluence patterns of the intrahepatic bile ducts at the hepatic hilum in the surgical specimens were studied. RESULTS: Confluence patterns of the right intrahepatic bile ducts were classified into 7 types. The right hepatic duct was absent in 4 of the 7 types and in 29 (26%) of the 110 livers. Confluence patterns of the left intrahepatic bile ducts were classified into 4 types. The left hepatic duct was absent in 1 of the 4 types and in 1 (2%) of the 55 livers. CONCLUSIONS: In harvesting the right liver from a donor without a right hepatic duct, 2 or more bile duct stumps will be present in the plane of transection in the graft in 3 patterns based on their relation to the portal vein. Accurate knowledge of the variations in the hepatic confluence is essential for successful living donor liver transplantation.

Bile Ducts↗

PubMed2004

[Benefit of percutaneous transhepatic portal vein embolization for extended hepatectomy].

Severely locally advanced biliary cancer requires extended hepatectomy in many cases. Percutaneous transhepatic portal vein embolization (PTPE) is effective to expand the residual liver volume and to avoid postoperative hepatic failure. The ratios of increase in the expected residual liver volume after PTPE are about 10% in cases with right lobar or right trisegment embolization and about 7% in cases with left trisegment embolization. After the introduction of the PTPE technique in our department, the morbidity rate from hepatic failure and mortality rate decreased from 33.3% to 23.8% and from 21.9% to 9.5%, respectively. The technique of PTPE has contributed to an improved survival rate for patients with severely advanced biliary cancer.

Embolization, Therapeutic↗

PubMed2004

[Epidural hematoma after an epidural block in a patient with no coagulopathy].

We report a case of epidural hematoma after a single epidural block. The patient was a 67-year-old woman with sciatica and osteoarthritis of the spine. She had no coagulopathy. She underwent a single epidural block without difficulty 3 times in 5 days. She had a lumbar MRI for an examination of the spine 4 days after the final epidural block. Subacute epidural hematoma of 0.8 x 1.5 x 3.0 cm was revealed on MRI at L 3-4. She had no new neurological symptoms. MRI 1 month later revealed a resolution of the hematoma. Epidural hematoma after an epidural block might occur in an outpatient with no bleeding tendency.

Acute Disease↗

PubMed2004

[Spinal anesthesia for 12 patients receiving home oxygen therapy].

From Jan 2001 to Nov 2003, 12 patients receiving home oxygen therapy (HOT) underwent surgery under spinal anesthesia at Okayama Rosai Hospital. The basic diseases for HOT were emphysema (n=8), interstitial pneumonia (n=1), asthma (n=1) and lung cancer (n=1). Mean FEV1.0 and FVC were 0.85 l and 1.97 l, respectively. Mean PaO2 and PaCO2 were 76.5 mmHg and 45.5 mmHg, respectively, under nasal oxygen of 1.67 l x min(-1). Perioperative complications occured in 3 cases. In case 5, postoperative heart failure occured and was easily treated with diuretics. In case 8, intraoperative hypotension (systemic blood pressure less than 80 mmHg) occured. In case 12, the patient developed dyspnea because of high spinal anesthetic level of T1. She was not intubated because PaO2, PaCO2 and pH were not deteriorated. Perioperative PaO2, PaCO2 and pH were stable and there were no pulmonary or morbid complications in all cases. It is important to assess not only pulmonary function but also cardiovascular status by echocardiography and general physical status by Hugh-Jones classification in order to avoid severe complications.

Aged↗

PubMed2003

Loss of p27(Kip1) accelerates DNA replication after partial hepatectomy in mice.

BACKGROUND: Liver regeneration after partial hepatectomy (PH) is accomplished by a synchronous replication of hepatocytes. Both positive and negative regulators of cyclin-dependent protein kinase (Cdk) have been implicated in hepatocyte proliferation, but their specific roles in vivo remain to be clarified. To investigate the specific role of p27(Kip1), a member of the Cip/Kip family of Cdk inhibitors, in cell-cycle regulation during liver regeneration, p27-knockout mice were studied after PH. MATERIALS AND METHODS: Under ether anesthesia, mice were subjected to 70% PH. Animals were sacrificed at intervals after the surgery, and the remnant liver was harvested and analyzed. RESULTS: In p27-deficient mice, the timing of DNA synthesis was significantly accelerated with a perturbation in the ordered distribution of proliferating cells in the hepatic lobule. p27 deficiency, however, did not affect the whole population of cycling cells, the number of apoptotic cells, or liver injury and mortality after PH. CONCLUSION: These data provide in vivo evidence that p27 functions as a brake in the "start" of the hepatocyte cell cycle, thereby coordinating temporally and spatially the onset of DNA synthesis of hepatocytes within the hepatic lobules.

Animals↗