Biomedical subjects

K Oda

Publications and source records attributed to K Oda.

At least 37 records · Page 2Linked to original sources

PubMed2001

Metastin suppresses the motility and growth of CHO cells transfected with its receptor.

We recently reported having identified of the ligand for an orphan G-protein-coupled receptor, hOT7T175, as the gene product (68-121)-amide of the metastasis suppressor gene KiSS-1. We further showed that the ligand, which we named "metastin," inhibits chemotaxis and invasion of Chinese hamster ovary (CHO) cells transfected with hOT7T175 cDNA (CHO/h175) in vitro, and pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. In the present study, we investigated the activity of metastin in CHO/h175 cells in greater detail. Metastin significantly suppressed motility in a chemotaxis assay and wound healing assay at 10-100 nM order concentrations. Two N-terminally truncated peptides, metastin(40-54) and metastin(45-54) inhibited the migration of CHO/h175 cells as potently as metastin itself. Metastin also inhibited the spreading, monolayer growth and colony formation in agar (0.8%) of CHO/h175 cells at 10-100 nM concentrations. These results indicate that metastin is a potent inhibitor of cell motility, leading to suppression of cell growth and antimetastatic activity, and suggest that low molecular chemical compounds could replace its activity as a novel antimetastatic agent.

Animals↗

PubMed2001

Cloning and rational mutagenesis of kexstatin I, a potent proteinaceous inhibitor of Kex2 proteinase.

Kexstatin I is a potent proteinaceous inhibitor of Kex2 proteinase (EC 3.4.21.61). In the present study we show the molecular cloning, primary structure determination and expression of the gene encoding kexstatin I. We also demonstrate its enhanced activity and specificity for Kex2 proteinase inhibition by rational mutagenesis. The cloned kexstatin I gene encoded a protein of 145 amino acid residues, including the 35-residue signal sequence for secretion. The amino acid sequence showed 52% identity with those of the Streptomyces subtilisin inhibitors (SSIs). Thus kexstatin I is the first SSI-family member that can inhibit Kex2 proteinase. The reactive site of the inhibitor was determined to be -Thr(69)-Lys(70) downward arrowGlu(71)-, where downward arrow indicates the reactive site. Because Kex2 proteinase generally shows the highest affinity for substrates with basic amino acid residues at the P(1) and P(2) sites, conversion of the Thr(69)-Lys(70) segment of the inhibitor into dibasic motifs was expected to result in enhanced inhibitory activities. Thus we constructed kexstatin I mutants, in which the Thr(69)-Lys(70) sequence was replaced by the Thr(69)-Arg(70), Lys(69)-Lys(70) and Lys(69)-Arg(70) sequences using PCR-based mutagenesis, and analysed them kinetically. Among these mutants, the Lys(69)-Arg(70) mutant was the most potent inhibitor. The K(i) for Kex2 proteinase was 3.2x10(-10) M, which was 140-fold lower than that of the inhibitor with the Thr(69)-Lys(70) sequence. Although kexstatin I could also inhibit subtilisin, the enhancement of inhibitory activity upon such mutations was specific for Kex2 proteinase inhibition.

Amino Acid Sequence↗

PubMed2001

A soft dual-port trocar for endoscopic subcutaneous surgery.

BACKGROUND: We developed a new trocar for endoscopic subcutaneous surgery and tested it in subfascial endoscopic perforator surgery (SEPS) for varicose veins of the lower leg. METHODS: The soft trocar is a y-shaped polyvinyl chloride bag equipped with two ports at one end and a flexible ring at the other end. We performed SEPS on 12 patients through a 2-cm incision below the knee. After dissection of the subfascial plane, the ring of the trocar was inserted beneath the fascia, and the subfascial cavity was inflated with CO2 gas. The perforating veins were divided with UltraShears (Autosuture, USSC, Norwalk, CT, USA) inserted through the second port of the trocar with an endoscope. RESULTS: There were no major device-related difficulties or wound complications. CONCLUSION: The soft trocar allowed both an endoscope and a surgical instrument to be inserted simultaneously in the tissue space through a single incision. This useful instrument may have applications in other endoscopic surgical procedures.

Carbon Dioxide↗

PubMed2001

Enzymatic characteristics and subcellular distribution of a short-chain dehydrogenase/reductase family protein, P26h, in hamster testis and epididymis.

A hamster sperm 26 kDa protein (P26h) is strikingly homologous with mouse lung carbonyl reductase (MLCR) and is highly expressed in the testis, but its physiological functions in the testis are unknown. We show that recombinant P26h resembles NADP(H)-dependent MLCR in the tetrameric structure, broad substrate specificity, inhibitor sensitivity, and activation by arachidonic acid, but differs in a preference for NAD(H) and high efficiency for the oxidoreduction between 5alpha-androstane-3alpha,17beta-diol (k(cat)/K(M) = 243 s(-1) mM(-1)) and 5alpha-dihydrotestosterone (k(cat)/K(M) = 377 s(-1) mM(-1)). The replacement of Ser38-Leu39-Ile40 in P26h with the corresponding sequence (Thr38-Arg39-Thr40) of MLCR led to a switch in favor of NADP(H) specificity, suggesting the key role of the residues in the coenzyme specificity. While the P26h mRNA was detected only in the testis of the mature hamster tissues, its enzyme activity was found mainly in the mitochondrial fraction of the testis and in the nuclear fraction of the epididymis on subcellular fractionation, in which a mitochondrial enzyme, isocitrate dehydrogenase, exhibited a similar distribution pattern. The enzyme activity of P26h in the two tissue subcellular fractions was effectively solubilized by mixing with 1% Triton X-100 and 0.2 M KCl, and enhanced more than 10-fold. The enzymes purified from the two tissue fractions exhibited almost the same structural and catalytic properties as those of the recombinant P26h. These results suggest that P26h mainly exists as a tetrameric dehydrogenase in mitochondria of testicular cells and plays a role in controlling the intracellular concentration of a potent androgen, 5alpha-dihydrotestosterone, during spermatogenesis, in which it may be incorporated in mitochondrial sheaths of spermatozoa.

Alcohol Oxidoreductases↗

PubMed2001

NMR structure of Streptomyces killer toxin-like protein, SKLP: further evidence for the wide distribution of single-domain betagamma-crystallin superfamily proteins.

A protein isolated from the culture supernatant of the soil bacterium, Streptomyces sp. F-287, exhibits cytocidal effects for both budding and fission yeasts, and causes morphological changes of yeasts and filamentous fungi. This protein, which was the first killer toxin-like protein for yeasts identified in the Streptomyces microorganism, was named SKLP (Streptomyces killer toxin-like protein). Since the amino acid sequence of the protein, as determined by sequential Edman degradations, seemed to be unique, we determined the structure by NMR spectroscopy. Although the actual target of SKLP in yeasts has not been determined yet, the structure might give us a clue to characterize the targets. The solution structure of SKLP determined by NMR, however, turned out to be a single-domain crystallin-like protein, with two Greek key motifs and a short extra beta-strand at the N terminus. The final ensemble of 20 NMR structures overlaid onto their mean coordinate with rmsd values of 0.32(+/-0.06) A for the backbone atoms involved in the secondary structure elements. As a yeast killer toxin, WmKT, isolated from the yeast strain Williopsis mrakii also has a Greek key beta-barrel fold, we have made a detailed comparison of the structural features of SKLP with the other crystallin superfamily proteins. It is very interesting that SKLP has a unique electrostatic potential distribution on the molecular surface. Namely, one surface of the beta-barrel fold in SKLP has a large negatively charged region, with an isolated positive charge of the Arg62 side-chain at the center. The edge of this surface is surrounded by positively charged residues, including Arg31, Arg65 and Arg74. The salient features of the charge distribution on this surface and the cluster of Arg residues might be related to the target binding of SKLP.

Amino Acid Motifs↗

PubMed2001

Bilirubin impairs bactericidal activity of neutrophils through an antioxidant mechanism in vitro.

BACKGROUND: Liver failure accompanied by hyperbilirubinemia after major hepatic resection is profoundly associated with septic complications. Although the immune dysfunction in cholestasis has been intensively investigated, the contribution of increased serum bilirubin to the impaired resistance to bacterial infection remains to be elucidated. Because bilirubin possesses an antioxidant activity, we hypothesized that bilirubin may scavenge reactive oxygen species (ROS) produced by neutrophils and consequently impair neutrophil bacterial killing. To address this, we evaluated the effects of bilirubin on the bactericidal activity of ROS or of neutrophils in vitro. MATERIALS AND METHODS: The antioxidant activity of bilirubin was determined using an ROS-sensitive fluorophore, dichlorofluorescin diacetate (DCFH-DA). Bilirubin concentration in the buffer solution was monitored spectorophotometrically after incubation with ROS. The effect of bilirubin on killing of Escherichia coli by ROS or by isolated human neutrophils was determined by counting the viable E. coli after incubation on nutrient agar. RESULTS: The bilirubin concentration in the buffer solution was decreased by the addition of hydrogen peroxide, especially in the presence of peroxidase or ferrous iron. DCFH-DA oxidation by ROS or activated neutrophils was inhibited by bilirubin in a dose-dependent manner. The bactericidal activity of ROS or of isolated neutrophils was significantly attenuated by bilirubin. CONCLUSIONS: Bilirubin impairs bactericidal activity of neutrophils through scavenging ROS. Increased levels of serum bilirubin may well be responsible for the impaired bacterial clearance in patients with hyperbilirubinemia.

Antioxidants↗

PubMed2001

An experimental study of selective intrahepatic biliary ablation with ethanol.

BACKGROUND: Few attempts have been made to investigate the feasibility of selective intrahepatic biliary ablation with absolute ethanol. METHODS: Through a catheter cannulated into the bile duct of the left lateral and median lobes (70% of total liver weight), 0.2 mL of absolute ethanol was injected into rats. RESULTS: The weight of the infused lobes decreased to less than 50% of the entire liver weight 14 days after treatment, while the weight of the noninfused lobes increased to 1.6-fold of the original value. This increase was associated with a markedly elevated Ki-67 labeling index. Both bile flow and bile acid excretion in the noninfused lobes significantly increased to more than twice the original values on Day 14. Histologically, the interlobular bile ducts of the infused lobes were destroyed. Ethanol also soaked through Glisson's capsule and destroyed hepatocytes, which were replaced by fibrous tissue and proliferating bile ductules without necrosis by Day 14. The portal veins and hepatic arteries supplying the infused lobes were structurally well preserved throughout the study period. CONCLUSION: Selective biliary infusion of ethanol can be performed safely without serious complications, achieving lobar ablation with contralateral hypertrophy of the liver.

Animals↗

PubMed2001

Auditory triggered mental imagery of shape involves visual association areas in early blind humans.

Previous neuroimaging studies identified a large network of cortical areas involved in visual imagery in the human brain, which includes occipitotemporal and visual associative areas. Here we test whether the same processes can be elicited by tactile and auditory experiences in subjects who became blind early in life. Using positron emission tomography, regional cerebral blood flow was assessed in six right-handed early blind and six age-matched control volunteers during three conditions: resting state, passive listening to noise sounds, and mental imagery task (imagery of object shape) triggered by the sound of familiar objects. Activation foci were found in occipitotemporal and visual association areas, particularly in the left fusiform gyrus (Brodmann areas 19-37), during mental imagery of shape by both groups. Since shape imagery by early blind subjects does involve similar visual structures as controls at an adult age, it indicates their developmental crossmodal reorganization to allow perceptual representation in the absence of vision.

Adult↗

PubMed2001

Acute myelogenous leukemia with PIG-A gene mutation evolved from aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome.

We report a patient with aplastic anemia (AA)-paroxysmal nocturnal hemoglobinuria (PNH) syndrome who developed acute myelogenous leukemia (AML). Flow cytometric analysis showed that the leukemic cells in the bone marrow lacked CD59 antigen on their surface and were positive for P-glycoprotein. Heteroduplex and single-strand conformation polymorphism analysis followed by sequencing of the leukemic cells in the bone marrow disclosed 1 frameshift-type mutation in exon 2 of the phosphatidylinositol glycan-class A (PIG-A) gene, which deductively produces truncated PIG-A protein. These findings provide direct evidence that the leukemic cells evolved from the affected PNH clone. Cytogenetic analysis in the bone marrow in each stage of AA-PNH, AML, and at relapse of AML showed normal, -7, and -7 plus -20, respectively, showing evidence of a clonal evolution. Because complete remission of AML was not achieved by intensive chemotherapies, allogeneic peripheral blood stem cell transplantation (PBSCT) from the patient's HLA-matched sister was performed successfully with recovery of CD59 antigen on bone marrow hematopoietic cells; however, leukemia relapsed 4 months after PBSCT. Leukemia derived from PNH may be resistant to intensive chemotherapy, and a highly myeloablative regimen may be required for stem cell transplantation to eradicate the PNH-derived leukemia clone.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Comparison of parametric FBP and OS-EM reconstruction algorithm images for PET dynamic study.

An ordered subsets expectation maximization (OS-EM) algorithm is used for image reconstruction to suppress image noise and to make non-negative value images. We have applied OS-EM to a digital brain phantom and to human brain 18F-FDG PET kinetic studies to generate parametric images. A 45 min dynamic scan was performed starting injection of FDG with a 2D PET scanner. The images were reconstructed with OS-EM (6 iterations, 16 subsets) and with filtered backprojection (FBP), and K1, k2 and k3 images were created by the Marquardt non-linear least squares method based on the 3-parameter kinetic model. Although the OS-EM activity images correlated fairly well with those obtained by FBP, the pixel correlations were poor for the k2 and k3 parametric images, but the plots were scattered along the line of identity and the mean values for K1, k2 and k3 obtained by OS-EM were almost equal to those by FBP. The kinetic fitting error for OS-EM was no smaller than that for FBP. The results suggest that OS-EM is not necessarily superior to FBP for creating parametric images.

Algorithms↗

PubMed2001

Use of 5-FU plus hyperbaric oxygen for treating malignant tumors: evaluation of antitumor effect and measurement of 5-FU in individual organs.

PURPOSE: Hyperbaric oxygen (HBO) has been shown to increase tumor radiosensitivity. Several reports indicate that it also increases sensitivity to alkylating agents, but other reports suggest that it may speed angiogenesis and tumor growth. To throw light on these questions, we investigated the effects of HBO and 5-fluorouracil (5-FU), individually and in combination, on Sarcoma 180 implants in mice. METHODS: We administered 5-FU at a dose of 0.75 mg/mouse six times per week and HBO at 2 atm absolute pressure for 90 min six times per week, both 17 times in total. In combination treatment, HBO was administered immediately after 5-FU injection. RESULTS: Over the treatment period, tumor diameter increased 277.8% in the untreated control group, 244.1% in the group receiving HBO monotherapy, 182.7% in the group receiving 5-FU monotherapy, and 138.5% in the group receiving combination therapy. Concomitant HBO increased accumulation of 5-FU in the tumors, liver, and kidneys, but not in the brain, of recipient animals. CONCLUSIONS: Based on the above results, we conclude that concomitant HBO enhances the effects of 5-FU.

Animals↗

PubMed2001

Visual function after foveal translocation with 360-degree retinotomy and simultaneous torsional muscle surgery in patients with myopic neovascular maculopathy.

PURPOSE: To assess functional and anatomical outcomes after foveal translocation with 360-degree retinotomy and simultaneous torsional muscle surgery in patients with myopic neovascular maculopathy. METHODS: Foveal translocation with 360-degree retinotomy was performed in 11 eyes of 11 patients with myopic neovascular maculopathy. Ten eyes had simultaneous torsional muscle surgery with recession of the superior oblique muscle and tucking of the inferior oblique muscle. Silicone oil removal with or without intraocular lens implantation was performed 2 to 8 weeks after the primary procedure. Visual acuity, binocular function, and degree of cyclotorsion were assessed preoperatively and postoperatively. Angles of retinal and globe rotation, distance of foveal shift, and surgical complications were also investigated. RESULTS: With a mean postoperative follow-up of 6.2 months (range, 3 to 13 months), vision improved (greater than 0.2 logarithm of minimal angle of resolution [logMAR] units) in eight eyes, was unchanged in two eyes, and worsened (greater than 0.2 logMAR units) in 1 eye. Seven of 11 eyes (64%) had a final visual acuity of 20/50 or better. Five patients developed or maintained binocular fusion, four patients continued to have suppression, and two patients developed diplopia that was managed by spectacles with Fresnel prisms. Subjective cyclotorsion was less than 8 degrees in 10 eyes. Mean retinal and globe rotations were 23.4 degrees and 19.8 degrees, respectively. Average size of the choroidal neovascular membrane was 0.8 disk diameter, whereas the average distance of foveal shift was 1.5 disk diameter. After the primary procedure, three eyes developed retinal detachment, one eye macular hole, and one eye proliferative vitreoretinopathy. These complications were successfully managed by additional surgery. CONCLUSION: Foveal translocation with 360-degree retinotomy is effective in restoring vision in some patients with myopic neovascular maculopathy. Although the development of torsional diplopia is generally obviated by simultaneous extraocular muscle surgery, a relatively high incidence of surgical complications should be taken into account with this procedure.

Aged↗

PubMed2001

Dynamic endorectal magnetic resonance imaging for local staging and detection of neurovascular bundle involvement of prostate cancer: correlation with histopathologic results.

OBJECTIVES: To assess the staging accuracy and detection of neurovascular bundle involvement by dynamic subtraction contrast-enhanced endorectal magnetic resonance imaging (MRI) in patients with localized prostate cancer. METHODS: In 38 patients with biopsy-proven prostate cancer, endorectal MRI was performed on a 1.5-Tesla magnetic resonance system using the dynamic technique with gadolinium-diethylenetriaminepentaacetic acid bolus enhancement. Two radiologists prospectively assessed the tumor involvement, localization, capsular penetration, seminal vesicle invasion, and neurovascular bundle involvement. All patients subsequently underwent radical prostatectomy, and the MRI findings were correlated with the histopathologic results. RESULTS: The overall accuracy of detecting cancer localization in the prostate was 72%. The detection of involvement in the peripheral zone had an 80% accuracy rate, but for lesions in the transition zone, the rate was 63%. The sensitivity and specificity of tumor detection was 81% and 79% for peripheral zone cancers and 37% and 97% for transition zone cancers, respectively. The accuracy rate, was 84%, 97%, and 97% for the detection of capsular penetration, seminal vesicle invasion, and neurovascular bundle involvement, respectively. CONCLUSIONS: Prostatic MRI with an endorectal surface coil using the dynamic technique more accurately detected tumor localization, capsular penetration, seminal vesicle invasion, and neurovascular bundle involvement than previously reported methods. The detection of tumor localization was more accurate in the peripheral zone than in the transition zone. This technique may be useful for the selection of patients for radical prostatectomy and, particularly, for identifying candidates for nerve-sparing surgery.

Aged↗

PubMed2001

Synthesis and structure-activity relationships of potent and orally active sulfonamide ETB selective antagonists.

The synthesis and structure activity relationships of a series of N-pyrimidinyl benzenesulfonamides as ETB selective antagonists are described. N-Isoxazolyl benzenesulfonamide 1a, previously reported, (1) was selected as a lead compound, and isosteric replacement of the isoxazole ring of 1a with a pyrimidine ring led to the discovery of the highly potent ETB selective antagonist 6e with oral bioavailability. Modification of the terminal aldehyde group at the 6-position of the pyrimidine ring was investigated, and malonate 15b and acylhydrazone 16f were found to be equipotent to aldehyde 6e. Compound 6e showed ETB antagonistic activity on in vivo evaluation.

Aldehydes↗

PubMed2001

Carboxyl proteinase from Pseudomonas defines a novel family of subtilisin-like enzymes.

The crystal structure of a pepstatin-insensitive carboxyl proteinase from Pseudomonas sp. 101 (PSCP) has been solved by single-wavelength anomalous diffraction using the absorption peak of bromide anions. Structures of the uninhibited enzyme and of complexes with an inhibitor that was either covalently or noncovalently bound were refined at 1.0-1.4 A resolution. The structure of PSCP comprises a single compact domain with a diameter of approximately 55 A, consisting of a seven-stranded parallel beta-sheet flanked on both sides by a number of helices. The fold of PSCP is a superset of the subtilisin fold, and the covalently bound inhibitor is linked to the enzyme through a serine residue. Thus, the structure of PSCP defines a novel family of serine-carboxyl proteinases (defined as MEROPS S53) with a unique catalytic triad consisting of Glu 80, Asp 84 and Ser 287.

Amino Acid Sequence↗

PubMed2001

Effects of pressure on the activity and spectroscopic properties of carboxyl proteinases. Apparent correlation of pepstatin-insensitivity and pressure response.

The pressure dependence of the activity and spectroscopic properties of four carboxyl proteinases were investigated. Two were pepstatin-sensitive carboxyl proteinases (porcine pepsin and proteinase A from baker's yeast) and two were pepstatin-insensitive carboxyl proteinases (from Pseudomonas sp. 101 (pseudomonapepsin; PCP) and Xanthomonas sp. T-22 (xanthomonapepsin; XCP)). The specificity constant [k(cat)/K(m(app))] of PCP and XCP for a synthetic peptide substrate showed only a slight decrease with increasing pressure, whereas pepsin and proteinase A showed substantial disactivation at higher pressures. The calculated apparent activation volume (Delta V((k(cat)/(K(m)) was about 1, 3, 13, and 14 mL.mol(-1) for PCP, XCP, pepsin, and proteinase A, respectively. The hydrolysis of acid-denatured myoglobin by the four carboxyl proteinases was only slightly affected by high pressure (except for proteinase A at 400 MPa), in contrast to the results for the peptide hydrolysis. In fact, PCP, XCP, and proteinase A actually showed slightly higher degradations of acid-denatured myoglobin at higher pressures. The residual activities of these enzymes after the incubation at high pressures implied a pressure-induced stabilization towards autolysis. The changes in the fourth derivative near-UV absorbance spectrum of the four enzymes in aqueous solution were measured at various pressures from 0.1 to 400 MPa. Upon an increase in pressure, the peaks from PCP and XCP red-shifted slightly, whereas pepsin and proteinase A blue-shifted substantially, thus indicating a more polar environment. The intrinsic fluorescence also decreased upon increasing pressure. However, the change for XCP was rather small, but the change for the other three was very large. The changes in the peak wavelength for pepsin and proteinase A were characteristic, and also indicated a more polar environment under high pressure. An analysis by the center of spectra mass (CSM) gave the Delta G and Delta V of transition as 9.8 kJ x mol(-1) and -24 mL x mol(-1) (pepsin) and 11.7 kJ x mol(-1) and -43 mL x mol(-1) (proteinase A), respectively, by assuming a simple two-state transition. The circular dichroism (CD) showed relatively small changes after 1-h incubations at 400 MPa, indicating that the secondary structures were largely maintained.

Animals↗

PubMed2001

Etiologic significance of defects in cholesterol, phospholipid, and bile acid metabolism in the liver of patients with intrahepatic calculi.

Intrahepatic calculi, highly prevalent in the Far East, including Japan, are characterized clinically by chronic proliferative cholangitis with frequent stone recurrences. Intrahepatic calculi consist of 2 groups, i.e., brown pigment stones, including a high cholesterol content, and cholesterol stones, with the former predominating. To gain insights into the pathogenesis of intrahepatic calculi, cholesterol and bile acid biosynthesis, as well as alterations in intracellular transport and/or canalicular secretion of phospholipid and bile acid were investigated in liver of patients with intrahepatic calculi. Enzyme activities of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase were increased (12.8 +/- 1.9 pmol/min/mg protein, mean +/- SEM vs. 5.5 +/- 0.4 in controls; P < .01) and cholesterol 7 alpha-hydroxylase activities were decreased (1.3 +/- 0.4 vs. 4.9 +/- 0.6; P < .01) in liver specimens of patients with brown pigment stones. In addition, messenger RNA (mRNA) levels of multidrug resistance P-glycoprotein 3 (MDR3 Pgp) and phosphatidylcholine transfer protein (PCTP) were markedly low in the liver specimens compared with the levels in specimens of control subjects, gallbladder stone patients, and patients with obstructive cholestasis. The protein levels and the immunohistochemical staining were decreased for MDR3 Pgp and PCTP in the liver. Consistently, the concentrations of phospholipid were markedly reduced in the hepatic bile from both affected and unaffected hepatic segments. In patients with intrahepatic calculi, biliary cholesterol supersaturation and the formation of cholesterol-rich brown pigment as well as cholesterol stones may be attributed to decreased hepatic transport and biliary secretion of phospholipids, in the setting of increased cholesterogenesis and decreased bile acid synthesis.

Adult↗

PubMed2001

Intraductal papillary neoplasia of the liver associated with hepatolithiasis.

Intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk (intraductal papillary neoplasia of liver [IPN-L]) resembling intraductal papillary mucinous neoplasm of pancreas is occasionally associated with hepatolithiasis. In this study, 136 cases of hepatolithiasis in Taiwan, between January 1998 and March 2000, and an additional 21 cases of IPN-L before December 1998, were examined histologically. IPN-L was found in 41 of 136 hepatolithiasis cases (30.1%). Sixty-two IPN-L cases (42 women and 20 men; age range, 59.8 +/- 10 years) were divided into 4 types (type 1, IPN-L with low-grade dysplasia, 23 cases; type 2, IPN-L with high grade dysplasia, 11 cases; type 3, IPN-L with in situ and microinvasive carcinoma, 13 cases; and type 4, IPN-L of types 2 and 3 with distinct invasive carcinoma, 15 cases). Intraductal spreading and glandular involvement were commonly observed in all types. About half of types 3 and 4 cases had mucobilia, and mucinous carcinoma was variably found in two thirds of group 4 patients. IPN-L frequently showed variable gastroenteric differentiation such as goblet cells and foveolar and colon-like metaplasia. IPN-L with goblet cells and colon-like metaplasia was frequently associated with overproduction of mucin and mucobilia (P <.01). In Japan, IPN-L was not frequent in hepatolithiasis (12 of 135 cases). In conclusion, IPN-L forms a spectrum of biliary neoplasm in hepatolithiasis. It often displays variable gastroenteric metaplasia and significant intraductal spread. IPN-L tends to progress to mucinous carcinoma. Formerly reported "mucin-producing intrahepatic cholangiocarcinoma" with a favorable prognosis is included in IPN-L.

Adult↗