Near real-time retroflexion detection in colonoscopy.

Colonoscopy is the most popular screening tool for colorectal cancer. Recent studies reported that retroflexion during colonoscopy helped to detect more polyps. Retroflexion is an endoscope maneuver that enables visualization of internal mucosa along the shaft of the endoscope, enabling visualization of the mucosa area that is difficult to see with typical forward viewing. This paper describes our new method that detects the retroflexion during colonoscopy. We propose region shape and location (RSL) features and edgeless edge cross-section profile (ECSP) features that encapsulate important properties of endoscope appearance and edge information during retroflexion. Our experimental results on 50 colonoscopy test videos show that a simple ensemble classifier using both ECSP and RSL features can effectively identify retroflexion in terms of analysis time and detection rate.

World-Wide Web-based graphical user interfaces for laboratory data.

OBJECTIVES: Electronic medical record systems permit collection of large amounts of medical information. Usually, information is presented in a fixed format, either as text or tables. Health care providers have to navigate this fixed format in order to find information useful for a specific patient-provider interaction. The main objective of this work was to allow the provider immediate access to specific laboratory information through the development of a highly customizable, graphical user interface to the Mayo Clinic laboratory information system. RESULTS: Here we describe this platform-independent, World-Wide-Web-based graphical user interface that allows the provider to see all or a predetermined panel of essential laboratory data in graphical format. Advantages include availability at internet-based workstations, immediate recognition of trends over time, ability to zoom in and out of specific periods of time, and detailed analysis of patient values in relationship to normal values. CONCLUSIONS: Web browser-based user interface allowing graphical display of laboratory data using Java technology was described. The connection to the Mayo Clinic laboratory information system combines cross-platform support for use on virtually any networked machine, interaction through a Web browser for ease of use, and a combination of the Perl and Java languages for powerful data processing and interactivity.

The prognostic value of histology in the assessment of patients with Budd-Chiari syndrome.

BACKGROUND/AIMS: It is unclear whether treatment of patients with Budd-Chiari syndrome (BCS) should be based on liver histology, as large histopathological studies have not been performed. We investigated the relationship between the histopathological findings and survival. METHODS: We studied the clinical features and findings on biopsy specimens in 45 patients with BCS who were admitted to four tertiary referral medical centers. Histological findings, i.e. congestion, necrosis, inflammation and fibrosis, were graded. Survival was assessed in relation to histological findings and clinical features at the time of diagnosis as well as in relation to subsequent treatment with or without portosystemic shunting. RESULTS: Centrilobular congestion, centrilobular necrosis, lobular inflammation and portal inflammation were not significantly related to survival. In addition, there was no association between either pericentral or periportal fibrosis and survival. Univariate analysis revealed that the prothrombin time and Child-Pugh score were significantly related to survival (P = 0.005 and Ptrend = 0.02, respectively). Multivariate analysis yielded the Child-Pugh score, serum alanine aminotransferase (ALT) and treatment with portosystemic shunting as independent prognostic indicators. CONCLUSIONS: We found no evidence for a relationship between early liver pathology and survival. Child-Pugh score, serum ALT and portosystemic shunting appeared to be prognostic indicators for patients with BCS.

The mitotic checkpoint protein hBUB3 and the mRNA export factor hRAE1 interact with GLE2p-binding sequence (GLEBS)-containing proteins.

The mRNA export factor RAE1 (also called GLE2) and the mitotic checkpoint protein BUB3 share extensive sequence homology in yeast as well as higher eukaryotes, although the biological relevance of their similarity is unclear. Previous work in HeLa cells has shown that human (h)RAE1 binds the nuclear pore complex protein hNUP98 via a short NUP98 motif called GLEBS (for GLE2p-binding sequence). Here we report that the two known binding partners of hBUB3, the mitotic checkpoint proteins hBUB1 and hBUBR1, both carry a region with remarkable similarity to the GLEBS motif of hNUP98. We show that the GLEBS-like motifs of mouse (m)BUB1 and mBUBR1 are sufficient for mBUB3 binding. mBUB3 lacks affinity for the hNUP98 GLEBS, demonstrating its binding specificity for GLEBS motifs of mitotic checkpoint proteins. Interestingly, mRAE1 does not exclusively bind to the GLEBS motif of hNUP98 and can cross-interact with the mBUB1 GLEBS. We show that full-length RAE1 and BUB1 proteins interact in mammalian cells and accumulate both at the kinetochores of prometaphase chromosomes. Our findings demonstrate that GLEBS motifs reside in mammalian nucleoporins and mitotic checkpoint proteins and apparently serve as specific binding sites for either BUB3, RAE1, or both.

Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience.

OBJECTIVES: The aims of this retrospective study were to assess the frequency with which we used different treatment modalities for patients with primary sclerosing cholangitis (PSC) and cholangiocellular carcinoma (CCA). METHODS: A total of 41 patients with known CCA complicating PSC with a median age of 49 yr (range, 27-75 yr) were identified from a group of 1009 patients (4%) with PSC seen over 10 yr at the Mayo Clinic. RESULTS: These patients received mainly five forms of treatment: 10 patients were treated with radiation therapy (RT) with or without 5-fluorouracil (5-FU) (seven with palliative and three with curative intent), nine with stent placement for cholestasis, 12 with conservative treatment, four with surgical resection (one of four received RT and 5-FU), and three patients with orthotopic liver transplantation and RT, with or without 5-FU. One patient was treated with 5-FU alone, one with photodynamic therapy, and one patient with somatostatin analog. A total of 36 patients died, whereas four (10%) patients survived (two with surgical resection, one with orthotopic liver transplantation and RT, and one with stent placement) during a median follow-up of 5.5 months (range, 1-75 months). One patient was lost to follow-up. CONCLUSIONS: In highly selective cases, resective surgery seems to be of benefit in PSC patients with CCA. However, these therapies are rarely applied to these patients because of the advanced nature of the disease at the time of diagnosis. Efforts should be directed at earlier identification of potential surgical candidates.

Endoscopic application of photodynamic therapy for cholangiocarcinoma.

BACKGROUND: Previous studies indicate that photodynamic therapy provides effective relief from biliary obstruction in advanced cholangiocarcinoma. This report describes a method of applying photodynamic therapy in the biliary tract by using accessories available in the United States. METHODS: Endoscopic retrograde cholangiography was performed to define the proximal and distal extent of intraductal tumor. Patients were injected with 2 mg/kg of sodium porfimer. Forty-eight hours later a commercially available cylindrical diffusing laser fiber was inserted into an 8F biliary catheter equipped with a 0.038 inch side-hole at its distal tip. After positioning of a 0.035 inch guidewire proximal to the biliary stricture, the preloaded catheter was advanced over the guidewire by using the monorail technique. Laser light was applied at a power of 400 mW/cm fiber for a total energy of 180 J/cm.(2) RESULTS: Fourteen treatments were performed on 6 patients with tumors of Bismuth types IV (n = 2), III (n = 3), or II (n = 1). By using the preloaded biliary catheter, adequate positioning of the laser fiber was achieved in all patients. A fracture of the diffuser tip occurred during 1 of the treatments. Two patients developed acute cholangitis and 2 patients experienced skin phototoxicity. CONCLUSIONS: Photodynamic therapy for cholangiocarcinoma is safe and technically feasible with a preloaded biliary catheter and a monorail technique for catheter positioning.

Improved diagnostic yield of endoscopic biliary brush cytology by digital image analysis.

OBJECTIVE: To evaluate the accuracy of digital image analysis (DIA) for distinguishing between benign and malignant strictures of the biliary tract. PATIENTS AND METHODS: Our pathology databank was used to identify all biliary brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography between June 1997 and June 1999. Corresponding medical records were reviewed to determine whether patients had benign or malignant strictures. Strictures were further classified into benign strictures with negative routine cytology, malignant strictures with negative routine cytology, and malignant strictures with positive routine cytology. Papanicolaou-stained smears of available brush cytology specimens were destained and then restained with Feulgen dye. Nuclear images were quantified for DNA content without knowledge of stricture type. DNA histograms were generated and ploidy results compared with the class of stricture. RESULTS: We analyzed 27 specimens from 69 confirmed benign or malignant strictures. Assuming that the presence of any aneuploid cells indicated malignancy, the sensitivity of DIA was 85%. Furthermore, aneuploid cells were detected by DIA in 13 of 16 specimens in which routine cytology was unrevealing. CONCLUSION: Ploidy assessment by DIA has potential to enhance the sensitivity of diagnosing malignant strictures compared with routine cytology alone.

Hepatic lymphangiomatosis mimicking polycystic liver disease.

Hepatic lymphangiomatosis is a rare disorder characterized by cystic dilatation of the lymphatic vessels in the hepatic parenchyma. It can occur in the liver alone, in the liver and spleen, or in multiple organs. Clinically, diagnosis can be difficult because of the rarity and protean manifestations of this disorder. We describe a 53-year-old woman with hepatic lymphangiomatosis in whom polycystic liver disease had been previously diagnosed. In addition, we review 12 cases of hepatic, splenic, and hepatosplenic lymphangiomatosis with or without systemic lymphangiomatosis and discuss the differential diagnosis.

Characterization and growth regulation of a rat intrahepatic bile duct epithelial cell line under hormonally defined, serum-free conditions.

Bile duct epithelial cells, or cholangiocytes, proliferate in vivo under a number of pathologic (i.e., partial hepatectomy) and pathophysiologic (i.e., bile duct ligation, malignant transformation) conditions. However, little is known about the possible growth factors that modulate these proliferative responses, in part because an in vitro model to study proliferation of nontransformed, normal cholangiocytes is not available. We report here the development of a rat cholangiocyte cell line (MMRC, minimal media-requiring rat cholangiocytes) that grows under hormonally defined, serum-free conditions on plastic and maintains a cholangiocyte phenotype. Morphologic as well as functional studies indicate that the cell line is polarized and actively transports fluid and electrolytes in an apical to basolateral direction. MMRC, when cultured for 24 mo. and passaged 80 times, have not undergone malignant transformation, because the cell line failed to grow under anchorage-independent conditions or in nude mice. Cellular proliferation is accelerated 2-8-fold by insulin, insulin-like growth factor 1, epidermal growth factor, and hepatocyte growth factor, growth factors known to stimulate tyrosine kinase receptors, and inhibited 2-10-fold by TGFbeta and IL-2. Glyco-conjugates of primary (i.e., cholic and chenodeoxycholic acid) and secondary bile acids (i.e., deoxycholic and lithocholic acid) do not alter proliferation at low concentration (1 microM), but are toxic at higher concentration (10 microM). In summary, we have developed and characterized a cholangiocyte cell line derived from normal rat liver, which grows under hormonally defined, serum-free conditions, maintains a nonmalignant, cholangiocyte phenotype, displays morphologic and functional features of polarity, and alters its proliferation rate in response to a variety of growth factors.

Applying World Wide Web technology to the study of patients with rare diseases.

Randomized, controlled trials of sporadic diseases are rarely conducted. Recent developments in communication technology, particularly the World Wide Web, allow efficient dissemination and exchange of information. However, software for the identification of patients with a rare disease and subsequent data entry and analysis in a secure Web database are currently not available. To study cholangiocarcinoma, a rare cancer of the bile ducts, we developed a computerized disease tracing system coupled with a database accessible on the Web. The tracing system scans computerized information systems on a daily basis and forwards demographic information on patients with bile duct abnormalities to an electronic mailbox. If informed consent is given, the patient's demographic and preexisting medical information available in medical database servers are electronically forwarded to a UNIX research database. Information from further patient-physician interactions and procedures is also entered into this database. The database is equipped with a Web user interface that allows data entry from various platforms (PC-compatible, Macintosh, and UNIX workstations) anywhere inside or outside our institution. To ensure patient confidentiality and data security, the database includes all security measures required for electronic medical records. The combination of a Web-based disease tracing system and a database has broad applications, particularly for the integration of clinical research within clinical practice and for the coordination of multicenter trials.

Cholangiocyte-specific rat liver proteins identified by establishment of a two-dimensional gel protein database.

The liver is composed of a variety of cells that form a functional unit involved in uptake, synthesis, metabolism, and secretion. Until recently, most studies examining liver function did not analyze the specific proteins expressed or functions performed by the multiple individual cell types that constitute the hepatic mass. In the last decade, novel isolation methods have been developed that allow the purification of liver cell populations highly enriched in one type of liver cell. Here, we present a detailed two-dimensional (2-D) protein map of rat bile duct epithelial cells (i.e., cholangiocytes) using a recently developed isolation procedure. In addition, we identify 27 major cholangiocyte proteins either by comparison to maps of known rat liver proteins (based on pI and Mr) or by tryptic digestion and microsequencing. Finally, we compare the relative abundance of individual proteins present in cholangiocytes to whole liver as well as hepatocyte-specific proteins. Our results show that cholangiocytes express a unique array of individual proteins. The cholangiocyte 2-D protein pattern is markedly different from that of isolated rat hepatocytes or whole rat liver, with high levels of proteins previously known to be expressed by cholangiocytes (e.g., cytokeratins, actins) as well as protein not previously demonstrated to be expressed at high levels (e.g., annexin V, selenium binding protein). We conclude that this cholangiocyte-derived, 2-D protein map will be a crucial resource for studies directed at our understanding of cholangiocyte physiology and pathobiology.

Kinetic and molecular identification of sodium-dependent glucose transporter in normal rat cholangiocytes.

While previous work has demonstrated that monosaccharides can be absorbed from bile, studies of sugar transport by the biliary, epithelia (i.e., cholangiocytes) are lacking. Using a novel model of polarized rat cholangiocytes in primary culture, designated normal rat cholangiocytes (NRC), we examined directly the uptake and transcellular transport of a nonmetabolizable monosaccharide, methyl alpha-D-glucopyranoside (AMG). When the apical or basolateral domain of cholangiocytes was exposed to radiolabeled AMG or sucrose (control), only apical absorption of AMG was evident. This apical uptake was time dependent, saturable, and significantly inhibited (> or = 90%) by removal of Na+ or in the presence of phlorizin (0.1 mM), a competitive inhibitor of the Na(+)-glucose cotransporter. The transcellular flux of AMG was also polar (i.e., apical to basolateral). Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of the transcript for the specific Na(+)-glucose cotransporter SGLT1 in NRC and in freshly isolated cholangiocytes but not in purified hepatocytes; in contrast, the transcript for SGLT2 was absent in all liver samples. In situ RT-PCR on frozen sections of normal rat liver showed that SGLT1 was expressed exclusively in cholangiocytes. Immunoblot analysis using a specific polyclonal antibody for the facilitative glucose transporter GLUT1 demonstrated it to be present in vesicles derived from NRC enriched in basolateral plasma membrane domains. Our data are consistent with the concept that SGLT1 is present on the apical domain of biliary epithelia and, in conjunction with GLUT1 on the basolateral domain, accounts for glucose absorption from bile.

Dysarthria and apraxia of speech associated with FK-506 (tacrolimus).

The immunosuppressive agent FK-506 (tacrolimus) is one of the agents most commonly used to prevent rejection after liver transplantation. Neurologic toxicity related to FK-506 has been reported, including speech disorders; however, a detailed analysis of the speech disorder associated with use of FK-506 has not been presented. Herein we describe a patient who exhibited mutism, then severe apraxia of speech with a concomitant hypokinetic, spastic, and ataxic dysarthria after administration of FK-506. His residual mixed dysarthria, without radiographic evidence of a structural lesion, suggests dysfunction of one or more neurochemical systems. The pathophysiologic mechanisms underlying this intriguing entity remain obscure.

Esophagitis associated with the use of alendronate.

BACKGROUND: Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone. Aminobiphosphonates can irritate the upper gastrointestinal mucosa. METHODS: We describe three patients who had severe esophagitis shortly after starting to take alendronate and also analyze adverse esophageal effects reported to Merck, the manufacturer, through postmarketing surveillance. RESULTS: As of March 5, 1996, alendronate had been prescribed for an estimated 475,000 patients worldwide, and 1213 reports of adverse effects had been received. A total of 199 patients had adverse effects related to the esophagus; in 51 of these patients (26 percent), including the 3 we describe in case reports, adverse effects were categorized as serious or severe. Thirty-two patients (16 percent) were hospitalized, and two were temporarily disabled. Endoscopic findings generally indicated chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Bleeding was rare, and stomach or duodenal involvement unusual. In patients for whom adequate information was available, esophagitis seemed to be associated with swallowing alendronate with little or no water, lying down during or after ingestion of the tablet, lying down during or after ingestion of the tablet, continuing to take alendronate after the onset of symptoms, and having preexisting esophageal disorders. CONCLUSIONS: Alendronate can cause chemical esophagitis, including severe ulcerations, in some patients. Recommendations to reduce the risk of esophagitis include swallowing alendronate with 180 to 240 ml (6 to 8 oz) of water on arising in the morning, remaining upright for at least 30 minutes after swallowing the tablet and until the first food of the day has been ingested, and discontinuing the drug promptly if esophageal symptoms develop.