Usefulness of endoscopic retrograde biliary biopsy using large-capacity forceps for extrahepatic biliary strictures: a prospective randomized study.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde biliary biopsy samples are frequently too small and inadequate, which makes histological interpretation difficult. We therefore evaluated the diagnostic usefulness of forceps with a larger-sized cup and compared this with standard forceps for biliary biopsy. PATIENTS AND METHODS: This prospective study included consecutive patients with extrahepatic biliary strictures who underwent retrograde biliary biopsy between March 2005 and March 2006 at the Toho University Ohashi Medical Center. The standard forceps used were 1.8-mm forceps (FB-39Q, Olympus, Tokyo, Japan) and the large-capacity forceps were 2.2-mm forceps (Radial jaw3, Boston Scientific Inc., Natick, Massachusetts, USA). Four randomized biopsy specimens were taken from each patient, two using each type of forceps. RESULTS: A total of 32 patients (30 with malignant biliary strictures and 2 with benign biliary strictures) were enrolled. The median size of the biopsy samples taken using the standard forceps was 0.68 mm (2) and that using the large-capacity forceps was 1.98 mm (2) ( P < 0.0001). Significant differences between the standard forceps and large-capacity forceps were observed in sensitivity (43 % vs. 70 %), adequacy of the specimens, and submucosal tissue sampling rate. CONCLUSIONS: Large-capacity forceps performed better than standard forceps in terms of size, adequacy of the sample, submucosal sampling rate, and detection of neoplasia.

Intradural microsurgery and extradural gamma knife surgery for hypoglossal schwannoma: case report and review of the literature.

There have been only 26 cases of hypoglossal schwannomas reported to originate intradurally and extend extradurally into the hypoglossal canal. This 31-year-old mother of two children presented with a 5-day history of progressive headache, nausea, vomiting and vertigo. Her neurological exam was significant for nystagmus and left tongue deviation with marked atrophy. An initial head CT revealed extensive left hypoglossal canal erosion with 4th ventricle compression. T1-weighted MR images with contrast revealed a 4x3 cm left cerebellopontine angle non-homogeneously enhancing mass with an intracranial cystic component and prominent extension into the eroded hypoglossal canal. A left lateral suboccipital craniotomy was performed for subtotal microsurgical resection of the intradural posterior fossa mass. A schwannoma was diagnosed after resection and gamma knife surgery (GKS) was performed three months later for the extradural residual tumor without further deficits. This is a rare report of a hypoglossal schwannoma in a young patient who was treated with a multimodality approach in order to minimize risks. A review of the literature and discussion of the respective benefits of microsurgery versus GKS and long-term follow-up issues are presented.

Usefulness of FDG-PET to diagnose intravascular lymphomatosis presenting as fever of unknown origin.

Intravascular lymphomatosis (IVL) is a rare systemic disease characterized by proliferation of lymphoid cells within the lumina of small arteries, veins, and capillaries. Diagnosis requires skin, liver, lung, bone marrow, renal, meningeal, or brain vessel biopsy but is often made only when the illness has progressed or post mortem because early involvement of organs was not evident. We report a case of IVL presenting as fever of unknown origin (FUO). In this case, gallium scintigraphy and computed tomography (CT) showed no evidence of malignancy, whereas (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased FDG uptake in the sternum, left and right vertebra, humerus, femur, and especially ilium. The diagnosis was made on iliac bone marrow biopsy examination. FDG-PET was useful for the detection of spread of disease in a patient with IVL suffering from FUO.

Comparison of duodenal stent placement with surgical gastrojejunostomy for palliation in patients with duodenal obstructions caused by pancreaticobiliary malignancies.

BACKGROUND AND STUDY AIMS: Palliative treatment for duodenal stenosis with an enteral stent is effective in enhancing the quality of life of patients with duodenal obstruction. There have been no thorough comparisons of duodenal stent placement with standard surgical gastrojejunostomy. The present study evaluated the outcome of duodenal stent placement and surgical gastrojejunostomy for palliation of duodenal stenosis caused by pancreaticobiliary malignancies. PATIENTS AND METHODS: Medical records for patients who underwent palliative enteral stenting during the past 9 years were retrospectively reviewed, and the patients' clinical outcome was compared with that in patients who underwent open surgical gastrojejunostomy during the same period. Patients who underwent prophylactic gastrojejunostomy were excluded from the study. RESULTS: Twenty patients (11 men, nine women; mean age 71.8 years) with pancreaticobiliary malignancy underwent palliative enteral stenting (stent group). Nineteen patients (12 men, seven women; mean age 68.7 years) with pancreaticobiliary malignancies underwent surgical gastrojejunostomy (bypass group). In the stent group, the diagnoses were 12 pancreatic cancers, six gallbladder cancers, one bile duct cancer, and one ampullary cancer. In the bypass group, the diagnoses were 14 pancreatic cancers and five gallbladder cancers. There were no significant differences between the two groups with regard to clinical background. Both procedures were successful. There were no differences between the two groups with regard to the technical or clinical success rates, patient survival, possibility of discharge, need for parenteral nutrition, or incidence of complications. However, the time from the procedure to resumption of food intake was shorter in the stent group than in the bypass group (1 day vs. 9 days; P < 0.0001). Improvement in the performance score after the procedure was observed more frequently in the stent group (65 % vs. 26.3 %; P < 0.05). In terms of the median hospital stay from the time of the procedure to the time of initial discharge home (12 patients vs. nine patients), there was no statistical difference (15 days vs. 30 days) due to the small size of the sample. There was no procedure-related mortality in either group. CONCLUSIONS: Palliative stent placement was more beneficial than surgical gastrojejunostomy in enhancing the quality of life of patients with duodenal obstruction due to pancreaticobiliary malignancies.

A new cannula with a flexible tip (Swing Tip) may improve the success rate of endoscopic retrograde cholangiopancreatography.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is sometimes unsuccessful because the anatomy of the papilla of Vater precludes cannulation by routine means. The efficacy of a new flexible tip cannula (the Swing Tip) was studied in patients in whom routine ERCP was unsuccessful. PATIENTS AND METHODS: The Swing Tip cholangiographic catheter has an articulation at its tip which allows the tip to be flexed from 90 degrees to 30 degrees. Routine cholangiography was successful in 175 of 195 patients in whom it was attempted between September 2000 and November 2001. ERCP with the Swing Tip catheter was attempted in the 20 patients in whom ERCP had failed. RESULTS: In 17 of 20 patients, we attempted to insert the Swing Tip catheter into the common bile duct to perform cholangiography. Insertion was successful in 11 patients and unsuccessful in six. There were no complications related to the procedure. CONCLUSION: The Swing Tip catheter is a useful adjunct to standard ERCP catheters for patient in whom standard techniques are unsuccessful.

Technical modifications and strategies for stenting gastric outlet strictures using esophageal endoprostheses.

BACKGROUND AND STUDY AIMS: The outcome of stenting gastric outlet stricture is favorable compared with a bypass operation which has significant morbidity and mortality. In Japan, this procedure is particularly complicated by a lack of enteral stents. We report some technical stratagems for stent placement for gastric outlet strictures. PATIENTS AND METHODS: Between February 1993 and July 2001, 23 patients with gastric outlet strictures (14 men, nine women; mean age 72 years) underwent stent placement using an esophageal stent system. The Ultraflex or Z-stents were used in 18 or five patients, respectively. With the Ultraflex, we increased the length of the delivery system. Some patients underwent stent placement with the help of endoscopic assistance with a grasping forceps or a home-made sheath. RESULTS: The metal stent was successfully inserted in all patients. There were no complications during the procedure. Migration occurred in two out of five patients treated with the Z-stent, whereas there was no migration in patients treated with the Ultraflex stent. In two patients, curable pancreatitis was caused by pressure on the duodenal papilla. One of these patients also experienced bile stasis which required biliary decompression. There were three cases of obstruction, caused by tumor ingrowth (1), hyperplasia (1) and stent fracture (1); recanalization by an additional stent placement and/or cutting stent filaments was successful. All the patients died, with a median survival period of 52 days. There was no procedure-related mortality. CONCLUSIONS: With some technical modification, stent placement for gastric outlet stricture, even using an esophageal stent, is feasible. This procedure offers good palliation with no major complications.

Successful repair of a damaged duodenal stent by cutting stent wires and placement of a second stent.

Duodenal stenting has been gradually established in recent years because it is less invasive than standard surgical procedures and produces a rapid therapeutic response. For palliation of both duodenal and biliary stenoses, double stenting may be performed. Duodenal stents offer a great advantage in allowing endoscopic retrograde cholangiopancreatography (ERCP) without the need for balloon dilation. When biliary stent dysfunction occurs, the patient undergoes diagnostic and/or therapeutic ERCP across the duodenal stent. We encountered a duodenal stent fracture in a patient who required repeated ERCPs for stent dysfunction. Duodenal stent fractures have not previously been reported. The damaged stent was successfully repaired by using a cutting wire filament and placing another duodenal stent coaxially with the first. Clinicians should be aware of the possibility of stent fracture following endoscopic procedures, such as an ERCP, that require passage through the stent. The procedure described in this report would be of significant benefit if a gastrointestinal stent is fractured and occluded by a broken part.

Fetal DNA diagnosis from maternal blood: PEP-TaqMan PCR analysis of a single nucleated erythrocyte (NRBC).

Development of a real-time quantitative TaqMan PCR assay permits the high-quality analysis of DNA or RNA. This study demonstrates the successful detection of single locus genes from single NRBCs, retrieved by micromanipulation of cells on a blood smear slide. Quantitative data in relation to the concentration of a single locus DNA amplified by PEP from a single NRBC are also provided. In summary, a PEP-TaqMan system can potentially be a powerful tool for noninvasive fetal DNA diagnosis through the use of maternal blood.

Microwave coagulation versus insertion of a second stent for occluded biliary metal stent.

BACKGROUND/AIMS: There is no consensus regarding optimal management of self-expandable metallic stent occlusion. We investigated the efficacy of microwave coagulation therapy for recanalization as compared to second stent placement. METHODOLOGY: Sixty patients with malignant obstruction of the common bile duct were treated with metal stent placement from January 1992 to July 1999. Of these, 13 patients subsequently developed stent occlusion due to tumor ingrowth. We compared stent patency and patient survival rates after microwave coagulation to those after insertion of a second stent. The influence of the duration of patency of the first stent on the second stent patency was also evaluated. RESULTS: Of the 13 patients with stent occlusion, 7 were treated with microwave coagulation therapy, and 6 with insertion of a second metal stent. In all cases, occluded stents were successfully recanalized without any complications. There was no significant difference in duration of first stent patency between the two groups. The median duration of second stent patency was prolonged in microwave-treated patients (152 days vs. 104 days, P > 0.05). The median duration of patient survival after last recanalizing procedure was also prolonged in microwave-treated patients (131 days vs. 78 days, P > 0.05). Microwave energy did not induce destruction of the stent filament. CONCLUSIONS: Microwave coagulation did not offer significantly longer duration of stent patency and patient survival compared to insertion of a second metal stent. However, this procedure is safe, feasible, and certainly as good as a second stent placement. It may be an alternative to insertion of a second stent within the occluded stent.

Transpapillary microwave coagulation therapy for recanalizing self-expandable metallic stents occluded by tumor ingrowth: initial experience.

Percutaneous microwave coagulation for recanalizing stents occluded by tumor ingrowth has been reported. With this technique, however, the percutaneous drain diminishes the quality of life in patients with unresectable tumors and a limited prognosis. Transpapillary microwave ablation was attempted in three patients with occluded stents. After a sheath had been inserted into the proximal hepatic duct across the occluded region, a microwave electrode was introduced into the intrahepatic duct via the sheath. We used microwave therapy with an output power of 40 W, based on our previous in vitro study. Except in one patient, the stents were successfully recanalized with one or two attempts. In one patient who underwent ablation in the intrahepatic duct, a 1.8-mm electrode enabled recanalization of the stent. In another who underwent ablation in the extrahepatic duct, however, a larger electrode was required. There were no procedure-related complications. Transpapillary microwave coagulation of occluded stents appears to be an alternative to percutaneous microwave coagulation with an electrode fitting the stent size. The technique might be easier with the use of a redesigned electrode with a guide wire lumen.

Knitted nitinol stent insertion for various intestinal stenoses with a modified delivery system.

BACKGROUND: Insertion of metallic stents for esophageal stenoses is well established, but these stents are technically difficult to place elsewhere in the GI tract. Moreover, major complications have occurred when metal stents with sharp ends have been placed in these locations. The currently available flexible, blunt-ended, knitted nitinol stent is intended for use only in the esophagus. Because its short delivery system cannot reach segments of the gut distal to the esophagus, the delivery device was modified to facilitate intestinal access, and its performance was evaluated in the treatment of malignant intestinal obstructions. METHODS: The Ultraflex delivery system was modified by connecting an additional plastic tube and a suture cord; the length was increased from 95 cm to 150 cm or more. Stents used were 18 to 23 mm in diameter, and 10 to 15 cm in length. A knitted metal stent was inserted by using the modified delivery system in 10 patients (7 men, 3 women, mean age 68 years); 8 with gastric outlet, 1 with jejunal, and 1 with proximal colonic obstruction. RESULTS: Metal stent insertion was successful in all patients with significant relief of symptoms and restoration of the ability to eat. The patient with a jejunal stent required placement of a second stent because of bending of the initial stent. No major complications (migration or perforation) occurred. CONCLUSION: This technique appears to facilitate placement of a metal stent with blunt ends in the duodenum, small intestine, and proximal colon. Manufacturers should offer blunt-ended stents with long delivery devices.

Novel, potent, and selective phosphodiesterase 5 inhibitors: synthesis and biological activities of a series of 4-aryl-1-isoquinolinone derivatives.

A novel class of potent and selective phosphodiesterase 5 (PDE5) inhibitors, 4-aryl-1-isoquinolinone derivatives, which have been designed by the comparison of the structure of cGMP and a previously reported 1-arylnaphthalene lignan, was disclosed. Among these compounds, methyl 2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-3-isoquinoline carboxylate dihydrochloride (36a) exhibited potent PDE5 inhibitory activity (IC(50) = 1.0 nM) with high isozyme selectivities (IC(50) ratio: PDE1/PDE5 = 1300, PDE2/PDE5 > 10 000, PDE3/PDE5 > 10 000, PDE4/PDE5 = 4700, PDE6/PDE5 = 28). Compound 36a also showed the most potent relaxant effect on isolated rabbit corpus cavernosum (EC(30) = 7.9 nM). Compound 63 (T-1032), the sulfate form of 36a, was selected for further biological and pharmacological evaluation of erectile dysfunction.

An efficient synthesis of the anti-asthmatic agent T-440: a selective N-alkylation of 2-pyridone.

6,7-Diethoxy-1-[1-(2-methoxyethyl)-2-oxo-1,2-dihydropyridin- 4-yl]naphthalene-2,3-dimethanol [T-440, (1)] is a potential anti-asthmatic agent based on selective phosphodiesterase 4 inhibition. It was necessary for the further evaluation of 1 to develop an efficient synthetic route for 1, especially the construction of the 1-(2-methoxyethyl)-2-pyridone moiety. We examined an N-selective alkylation of pyridone derivative (2) in basic media. 2-Methoxyethylation of 2 with 2-methoxyethyl iodide utilizing LiH as the base gave predominantly an N-alkyl pyridone derivative (3a) in 82% yield (N/O-alkylation=92/8), which is compatible with an ab initio calculation of transition-state structures for the methylation of 2-pyridone. Single crystallization of a crude mixture of 3a and 4a furnished pure 3a, which is a key synthetic intermediate of 1.

1-Arylnaphthalene lignan: a novel scaffold for type 5 phosphodiesterase inhibitor.

1-Arylnaphthalene lignan, which had been reported as a PDE4 inhibitor by Iwasaki, was disclosed as a new structural class of PDE5 inhibitors. The structural requirements for potent and specific PDE5 inhibition were revealed in a 1-arylnaphthalene lignan series, in which 1-(3-bromo-4, 5-dimethoxyphenyl)-5-chloro-3-[4-(2-hydroxyethyl)-1-piperazinylcarbon yl]-2-(methoxycarbonyl)naphthalene hydrochloride (27q) showed the most potent and specific inhibition (PDE5 inhibition IC50 = 6.2 nM, selectivity for PDE5 against PDE1, -2, -3, and -4 >16 000). It is noteworthy that 27q has the best selectivities against PDE isoforms among PDE5 inhibitors so far reported. Compound 27q exhibited almost the same relaxant effects on rat aortic rings as sodium 1-[6-chloro-4-[(3, 4-methylenedioxybenzyl)amino]quinazolin-2-yl]piperidine-4-ca rboxylate (35) (27q, EC50 = 0.10 microM; 35, EC50 = 0.20 microM) and was selected for further biological evaluation.

Novel, potent, and selective phosphodiesterase-4 inhibitors as antiasthmatic agents: synthesis and biological activities of a series of 1-pyridylnaphthalene derivatives.

The structural requirements for potent and selective PDE4 inhibition were revealed in a 1-pyridylnaphthalene series, and the best compound (3kg, T-2585.HCl) was chosen for further biological evaluation (PDE4 inhibition IC50 = 0.13 nM, selectivity PDE3/4 ratio = 14 000). Compound 3kg showed potent antispasmogenic activities (ED50 = 0.063 mg/kg for reduction of antigen-induced bronchoconstriction, intravenously; ED50 = 0.033 mg/kg for reduction of histamine-induced bronchoconstriction, intraduodenally) in guinea pigs with little cardiovascular effects. Furthermore, 3kg induced significantly weaker emetic effects than RP73401 after oral administration in ferrets and intravenous administration in dogs (3kg, none of 4 ferrets vomited at a dose of 10 mg/kg, po and none of 8 dogs vomited at a dose of 0.3 mg/kg, iv; RP73401, 4 of 8 ferrets vomited at a dose of 3 mg/kg, po and 6 of 8 dogs vomited at a dose of 0.3 mg/kg, iv); that is compatible with the lower affinity for the high-affinity rolipram binding site (3kg, 2.6 nM; RP73401, 0. 85 nM). This may imply that 3kg has an improved therapeutic ratio because of a broad margin between the Ki value of binding affinity and the IC50 value of PDE4 inhibition (ratio = 0.050).