Development of a PET/EPRI combined imaging system for assessing tumor hypoxia.

Precise quantitative delineation of tumor hypoxia is essential in radiation therapy treatment planning to improve the treatment efficacy by targeting hypoxic sub-volumes. We developed a combined imaging system of positron emission tomography (PET) and electron para-magnetic resonance imaging (EPRI) of molecular oxygen to investigate the accuracy of PET imaging in assessing tumor hypoxia. The PET/EPRI combined imaging system aims to use EPRI to precisely measure the oxygen partial pressure in tissues. This will evaluate the validity of PET hypoxic tumor imaging by (near) simultaneously acquired EPRI as ground truth. The combined imaging system was constructed by integrating a small animal PET scanner (inner ring diameter 62 mm and axial field of view 25.6 mm) and an EPRI subsystem (field strength 25 mT and resonant frequency 700 MHz). The compatibility between the PET and EPRI subsystems were tested with both phantom and animal imaging. Hypoxic imaging on a tumor mouse model using 18F-fluoromisonidazole radio-tracer was conducted with the developed PET/EPRI system. We report the development and initial imaging results obtained from the PET/EPRI combined imaging system.

Comparative study of percutaneous nephrostomy using catheters with and without locking strings.

BACKGROUND: Although it is generally felt that a catheter with a locking string can achieve better fixation and thus prevent catheter displacement, no formal study has ever substantiated this. METHODS: We retrospectively reviewed the charts from 80 patients (mean age of 64.6 ± 14.76 y) who underwent percutaneous nephrostomy (PCN) over a 1-year period. RESULTS: Most patients had catheters without locking strings and only 17 patients (21.3%) had catheters with locking strings. The median duration of catheter placement was 29 days (interquartile range 14 - 57 d). There were no significant differences in patients' characteristics or catheter outcomes between catheters with and catheters without locking strings (p > 0.05). In addition, no significant difference in the catheter 90-day survival between catheter types was found (log rank test, p = 0.638). On univariate analysis, tumor as an indication for PCN (p = 0.018), obstruction (p = 0.021) and displacement (p = 0.007) were associated with reduced catheter survival. The multivariate analysis indicated that tumor as an indication for PCN (HR: 0.28, 95% CI: 0.13 - 0.63, p = 0.002), obstruction (HR: 0.25, 95% CI: 0.08 - 0.77, p = 0.015) and catheter displacement (HR: 0.09, 95% CI: 0.03 - 0.31, p < 0.001) were independent hazard factors for reduced catheter 90-day survival. CONCLUSION: No significant difference in either complication rate or 90-day survival was found between catheters with or without locking strings. These findings may prove helpful to the clinician in deciding the type of catheter to use during PCN.

Hirschsprung's disease, a rare precipitating factor in neonatal perforated Meckel's diverticulum.

Perforation of Meckel's diverticulum (MD) during the neonatal period may occur in the presence of distal colon obstruction. Herein, we describe a unique case of a 2-day-old infant that presented with pneumoperitoneum, in which a perforated MD was induced by distal intestinal obstruction secondary to total colonic aganglionosis. In the setting of neonatal perforated MD found intraoperatively, the determination of the possible precipitating etiology is necessary. The clinical history of delayed passage of meconium is emphasized, and either a rectal or colon biopsy is recommended intraoperatively to avoid overlooking the associated presence of Hirschsprung's disease.

The role of transcatheter arterial embolization for patients with unresectable hepatocellular carcinoma: a nationwide, multicentre study evaluated by cancer stage.

BACKGROUND: Transcatheter arterial embolization is a major palliative treatment for unresectable hepatocellular carcinoma, but the survival benefit of transcatheter arterial embolization is controversial. AIM: To evaluate the role of transcatheter arterial embolization in different stage of unresectable hepatocellular carcinoma and to select patients who can get the best benefit from the treatment. METHODS: From 1991 to 1995, 476 patients who had unresectable hepatocellular carcinoma from four medical centres in Taiwan were enrolled. Among them, 425 underwent transcatheter arterial embolization, and 51 received supportive treatment alone. The survivals between the two groups were compared. RESULTS: Among the 476 patients, transcatheter arterial embolization can significantly prolong survival. The 1-, 2-, and 5-year survival rates for patients who underwent transcatheter arterial embolization were 60.2%, 39.3%, and 11.5%; and the rates for patients who underwent supportive treatment were 37.3%, 17.6%, and 2%, respectively (P = 0.0002). The survival benefit of transcatheter arterial embolization was observed in patients between Cancer and the Liver Italian Program 0 and Cancer and the Liver Italian Program 4. In multivariate analysis, transcatheter arterial embolization, tumour size <5 cm and earlier Cancer and the Liver Italian Program stage were independent factors associated with a better survival. CONCLUSIONS: For patients who fulfilled the criteria of transcatheter arterial embolization, embolization can serve as a primary treatment for patients with unresectable hepatocellular carcinoma. The survival benefit of transcatheter arterial embolization is regardless of tumour stages.

Sclerosant extravasation as a complication of sclerosing endotherapy for bleeding gastric varices.

We report here the case of a 65-year-old woman who suffered intraperitoneal sclerosant leakage after endoscopic injection sclerotherapy for bleeding gastric varices. In total, 3 ml of N-butyl-2-cyanoacrylate and Lipiodol mixture was injected. The patient developed mild fever and pain over the left upper quadrant and flank after the procedure. In addition to a Lipiodol-filled gastric varix, the imaging studies disclosed a wide spread of Lipiodol over the left peritoneal cavity. The patient was kept fasting with parenteral antibiotics and nutrition. She responded well to the treatment, and all of the symptoms had subsided 6 days later.

Meckel's diverticulum associated with ileal volvulus in a neonate.

A symptomatic Meckel's diverticulum (MD) may manifest as an intestinal obstruction secondary to a volvulus. We describe a case of a meconium-impacted MD associated with inflammatory adhesions to adjacent viscera that presented as an intestinal obstruction in a 4-h-old infant secondary to an ileal volvulus with resultant infarction of the diverticulum and ileal segment.

Hepatic angiomyolipoma with concomitant hepatocellular carcinomas.

Angiomyolipoma is a rare lipomatous tumor in the liver. Definitive preoperative diagnosis is becoming easier by the use of ultrasonography, computed tomography, and magnetic resonance imaging techniques. Nonsurgical treatment has been advocated for its benign nature. However, recently we encountered one case of hepatic angiomyolipoma with two concomitant hepatocellular carcinomas on a hepatitis B carrier. Although his serum alpha-fetoprotein was normal, under the above impression these lesions were resected. The pathologic findings showed a typical angiomyolipoma and two well-differentiated hepatocellular carcinomas with marked fatty metamorphosis. This is the first report of angiomyolipoma with concomitant hepatocellular carcinomas in the literature. Nonsurgical treatment of angiomyolipoma in an endemic area for hepatocellular carcinoma should proceed with caution because cases of fat-rich minute hepatocellular carcinomas will make the diagnosis difficult.

Von Willebrand factor-cleaving protease activity and proteolysis of von Willebrand factor in bone marrow transplant-associated thrombotic microangiopathy.

INTRODUCTION: Thrombotic microangiopathy (TM) of the fulminant type occurring in patients following bone marrow transplant (BMT) has clinical manifestations that are similar to thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome, but the outcome is generally fatal despite conventional therapy. Idiopathic acquired TTP has been associated with IgG inhibitors to the cleaving protease of von Willebrand factor (vWF) in plasma. In this study, we investigated the role of the vWF protease and vWF proteolysis in the pathogenesis of BMT-associated TM of the fulminant type. METHODS: vWF antigen level, vWF multimeric pattern, and vWF metalloprotease activity were investigated in the plasma samples of six consecutive patients with acute BMT-associated TM. Histologic and immunohistochemical studies were also performed on autopsy kidney specimens from four of the patients. All six patients had the fulminant type of the disorder with a fatal outcome and none of the patients responded to plasma infusion. RESULTS: The vWF-cleaving protease activity in plasma was normal in all patients. However, analysis of the vWF multimeric pattern showed a decrease of high molecular weight multimers. The decrease of large multimers may be caused by vWF-platelet binding as well as shear enhanced proteolysis of vWF. In the four patients who had an autopsy, a pattern of arteriolar thrombosis, distinct from that of TTP, was detected in the kidneys. CONCLUSION: These findings suggest that BMT-associated TM of the fulminant type is a heterogeneous process and distinct from TTP in pathogenesis. Analysis of vWF protease and vWF multimeric distribution are valuable tools in making the distinction between BMT-associated TM and TTP.

Defective von willebrand factor activity detected by the filterometer in three clinical conditions.

When exposed to high levels of shear in a filterometer, platelets bind to von Willebrand factor (vWF) via receptors Ib and IIb/IIIa, forming aggregates that block the filteromer. In this study we used the filterometer to explore the mechanisms by which abnormal vWF-platelet interaction might occur. In the first phase of the study, the global vWF-platelet interaction in native blood was investigated. In the second phase, to eliminate the difference that platelets might contribute, samples of platelet-poor plasma from test individuals were added to normal control blood and the mixtures were investigated by the filterometer. The filterometer results were adjusted for the antigen concentrations to obtain vWF potency ratios. Sodium dodecyl sulphate (SDS) agarose gel electrophoresis and SDS-Polyacylamide gel electrophoresis (PAGE) were used to analyze multimeric size and proteolytic profiles of vWF. Pregnancy was associated with high platelet retention, high vWF antigen concentration, normal multimeric size distribution, but decreased vWF potency ratios. The plasma samples of pregnancy contained one 183-kDa fragment not detected in normal plasma. These results suggested that in pregnancy, platelets were highly active. However, presumably due to abnormal proteolytic cleavage, vWF potency was decreased. This decrease in vWF potency might minimize the risk of thrombosis in association with highly active platelets. Renal transplant patients had normal platelet retention but high vWF levels. The plasma vWF contained normal multimers. A decrease in vWF potency, presumably caused by toxic inhibitors in the plasma, was detected. Aortic valve stenosis patients had decreased platelet retention, normal or slightly increased vWF antigen concentration and a decrease in large multimers. As a result, the vWF potency was markedly decreased. However, the results obtained with the filterometer became normal when the studies were repeated 3 months postpartum, when renal function had improved after transplantation, and when the aortic valves were corrected by surgery. These results indicate that the filterometer is a useful tool for elucidating the mechanisms by which vWF-platelet interaction might be impaired in various clinical conditions.

Liver, spleen and tumor volume measured by personal computer.

BACKGROUND/AIMS: Computed tomography (CT) scans are common examinations for patients with chronic liver diseases. To quantitate the organ or tumor volume from the scans and to accomplish the task in an efficient way with the most economic equipment, we developed a system based on a personal computer. METHODOLOGY: We used color-markers and transparency to sketch the edges of liver, hepatoma, and spleen. Each organ or tumor of interest is marked out by fine-point markers on pieces of transparency. The sketch was scanned into a digitized image format on a personal computer (Pentium 133). The calculation involves edge detection, three-dimensional reconstruction, and voxel counting. By using summation-of-the-area and trapezoid approximation technique, the voxels of each structure are counted. In this study, we illustrate the potential application in the management of a hepatic cancer patient. RESULTS: After digitalization, the data size of CT images is about 1 to 1.5 megabytes. It takes less than 5 min to complete volume calculation. CONCLUSIONS: By this method, tumor load before and after chemotherapy can be estimated easily and accurately. This would be helpful in clinical practice.

Disseminated Mycobacterium genavense infection in a patient with acquired immunodeficiency syndrome: first case report in Taiwan.

Mycobacterium genavense is a recently described fastidious mycobacterium identified as a pathogen causing disseminated infection in patients with advanced human immunodeficiency virus (HIV) disease. In this report, we describe the first reported case of disseminated M. genavense infection in a patient with acquired immunodeficiency syndrome (AIDS) in Taiwan. A 22-year-old Chinese man was found to be seropositive for HIV at age 18, in 1993. In 1997, he presented with abdominal pain, weight loss, low CD4 lymphocyte count, hepatomegaly, and generalized lymphadenopathy. Microscopic examination of a biopsy specimen from an inguinal lymph node showed both ill- and well-formed noncaseating granulomas. Numerous acid-fast bacilli were present in the histiocyte cytoplasm. Although the organism did not grow on conventional solid media used in our laboratory, two molecular biology techniques, including polymerase chain reaction (PCR) followed by sequencing of 16S rRNA, and PCR together with restriction enzyme fragment polymorphism analysis, confirmed the M. genavense infection. The patient's abdominal symptoms responded well to a chemotherapy regimen that included ethambutol, ciprofloxacin, and clarithromycin, and he survived more than 6 months after diagnosis. However, the lymphadenopathy was still present at his final follow-up. Our report indicates that disseminated infection with M. genavense should be added to the list of differential diagnoses of secondary infections in advanced AIDS patients in Taiwan.

An automatic diagnostic system for CT liver image classification.

Computed tomography (CT) images have been widely used for liver disease diagnosis. Designing and developing computer-assisted image processing techniques to help doctors improve their diagnosis has received considerable interests over the past years. In this paper, a CT liver image diagnostic classification system is presented which will automatically find, extract the CT liver boundary and further classify liver diseases. The system comprises a detect-before-extract (DBE) system which automatically finds the liver boundary and a neural network liver classifier which uses specially designed feature descriptors to distinguish normal liver, two types of liver tumors, hepatoma and hemageoma. The DBE system applies the concept of the normalized fractional Brownian motion model to find an initial liver boundary and then uses a deformable contour model to precisely delineate the liver boundary. The neural network is included to classify liver tumors into hepatoma and hemageoma. It is implemented by a modified probabilistic neural network (PNN) [MPNN] in conjunction with feature descriptors which are generated by fractal feature information and the gray-level co-occurrence matrix. The proposed system was evaluated by 30 liver cases and shown to be efficient and very effective.

Infantile hemangioendothelioma with a highly elevated serum alpha-fetoprotein level.

Infantile hemangioendothelioma is the most common vascular tumor in infancy. A three-month-old infant was admitted to the hospital for hepatomegaly. Abdominal ultrasonography, a CT-scan, and MRI studies demonstrated bilateral diffuse hepatic nodules, which were characteristic of hepatic hemangioendothelioma. A highly elevated alpha-fetoprotein (AFP) level misled us to an impression of hepatoblastoma, but the pathology report through an open biopsy disclosed a liver hemangioendothelioma. The patient responded to methylprednisolone therapy. A follow-up sonogram revealed regression of the hepatic masses. This case emphasizes that an elevated AFP level of up to 400 ng/ml is normally found in some neonates until two months of age. Careful interpretation of this value is very important, especially when it is associated with a hepatic tumor. Herein, we present a case of infantile hemangioendothelioma in a three-month-old boy with a highly elevated serum AFP.

Proteolytic cleavage of recombinant type 2A von Willebrand factor mutants R834W and R834Q: inhibition by doxycycline and by monoclonal antibody VP-1.

The susceptibility of recombinant type 2A von Willebrand factor (vWF) to a recently identified plasma metalloproteinase and the potential application of proteolysis inhibition in the treatment of the disease were investigated. Two recombinant type 2A vWF mutants, R834W and R834Q, were spontaneously cleaved by the partially purified plasma proteinase to smaller forms. When treated with guanidine HCI, both the wild-type and the R834W mutant vWF exhibited a biphasic change in proteolytic susceptibility, reaching the same maximum cleavage at 1.25 mol/L guanidine HCI. Proteolysis of the recombinant vWF generated the same 350-kD and 200-kD species (dimers of the 176-kD and 140-kD fragments, respectively) as those found in normal plasma. The proteinase activity was inhibited by doxycycline, with an IC50 of approximately 0.25 mmol/L. The inhibitory activity of doxycycline was related to its metallic cation binding activity. Susceptibility of the recombinant vWF to the proteinase was inhibited by monoclonal antibody VP-1 (directed against residues 828-842 of the vWF polypeptide), but not by two other monoclonal antibodies M13 and M31. The spontaneous susceptibility to proteolytic cleavage may account for the lack of large multimers in type 2A von Willebrand disease (vWD), and the results with tetracyclines and monoclonal antibody VP-1 offer new strategies for developing specific treatment of type 2A vWD.

Self-expandable metallic stents in the management of malignant biliary obstruction.

To overcome problems with conventional plastic endoprostheses, a study was conducted to determine the clinical efficacy of self-expandable metallic stents in the palliative treatment of malignant biliary obstruction. From May 1994 to March 1995, 19 self-expandable metallic stents were implanted in 13 consecutive patients with malignant obstructive jaundice due to cholangiocarcinoma (four patients), ampullary carcinoma (six), pancreatic carcinoma (one), and hepatic hilar lymph node metastasis (two). All patients underwent percutaneous transhepatic biliary drainage followed by stent insertion, except for two patients where the T-tube tract was used as access and another with previous placement of a polyethylene internal-external drainage catheter for more than 6 months. When both lobes of the biliary system were to be drained, stents were placed either side by side through punctured, separate hepatic ducts or, using a T configuration, through a single transhepatic tract. Percutaneous transhepatic stent placement was technically successful in all patients. After a mean follow-up of 5.9 months (range, 1-10 mo), 10 of 13 patients were still alive while three had died of nonprocedure-related causes. In 10 patients, total serum bilirubin levels decreased significantly (from 136.8 +/- 157 mumol/L to 34.2 +/- 22.2 mumol/L), while it increased in three patients. Two patients had stent occlusions at 2 and 3 months after stent placement, which required intervention. The overall patency period ranged from 1 to 9 months (mean, 5.1 mo). Our results confirm that the use of metallic stents is effective in the palliative treatment of malignant jaundice.

Suprahepatic gallbladder and right lobe anomaly of the liver in patients with biliary cancers.

The suprahepatic region is a rare ectopic location of the gallbladder. It usually combines with right lobe anomaly of the liver. Here we report two unusual cases of suprahepatic gallbladder with agenesis or hypogenesis of the right lobe of the liver and biliary cancer. A patient with a gallbladder tumor was admitted to our emergency room with acute cholecystitis and liver abscess. Imagining examinations and operation confirmed the suprahepatic position of gallbladder, agenesis of the right lobe, and dissemination of gallbladder cancer. In the patient with cholangiocarcinoma, CT scans and percutaneous transhepatic cholangiography documented the presence of a hilar tumor and hypogenesis of the right lobe. Both of these patients died from biliary tract cancer soon after operation.

Simple, effective procedure with few complications for esophageal varices.

The surgical morbidity, mortality, and effectiveness of a modified nonshunting operation that includes splenic artery division instead of splenectomy, devascularization, and esophageal transection (SAD group) were evaluated. Eighteen cirrhotic patients with varices who underwent this modified procedure were compared with 54 patients treated with a conventional nonshunting operation (splenectomy group). Results show that immediate effects on portal pressure and preservation of portal perfusion between the two groups were similar. The operative time is shorter (p < 0.05), and the bleeding amount is less (p < 0.005) in the SAD group than in the splenectomy group. No surgical mortality and no major complications were noted in the SAD group. A surgical mortality of 2.3% and 30% was noted for the elective and emergency operations of the splenectomy group, respectively. There was no encephalopathy in the SAD group but one in the splenectomy group. Recurrent bleeding occurred in three patients of the splenectomy group 1 year after surgery but none in the SAD group. These data indicate that this modified procedure is a simple and effective operation with few complications for esophageal varices.

Shear stress enhances the proteolysis of von Willebrand factor in normal plasma.

While von Willebrand factor (vWF) is secreted from endothelial cells as a very large polymer, it circulates as a series of multimers that are reducible to a 225-kD polypeptide and three proteolytic fragments of 189, 176, and 140 kD. Cleavage at the Tyr-842/Met-843 bond of the vWF polypeptide creates the 140- and 176-kD fragments. In the process of understanding vWF multimer formation, the role of shear stress in vWF proteolysis was investigated in this study. A shear-rate-dependent loss of the largest multimers was observed when normal plasma was perfused through long capillary tubings achieving shear rates normally encountered in the circulation. The shear-dependent vWF change was not observed when purified vWF or normal plasma containing calcium chelator EGTA or EDTA was perfused. As the large multimers decreased, an increase in the smaller multimers, including 200- and 350-kD bands, was detected. Elution and immunoblotting studies with peptide-specific antibodies LJ-7745 and VP-1 showed that the 200-kD band was a dimer of the 140-kD fragment, whereas the 350-kD band was a dimer of the 176-kD fragment. When analyzed after disulfide bonds were reduced, sheared plasma showed an increase in the 176- and 140-kD fragments, but not the 189-kD fragment. Finally, shearing of purified vWF enhanced its proteolytic cleavage when it was subsequently incubated with the cryosupernatant fraction of normal plasma or with cathepsin G, a leukocyte granule serine protease. These results show that shear stress is capable of enhancing the susceptibility of vWF to proteolytic cleavage. It promotes vWF proteolysis in normal plasma at a site that generates the 140-kD/176-kD fragments, leading to a decrease in multimer size. Shear stress might be involved in modulating the size of vWF in the circulation.

Influence of paraesophageal venous collaterals on efficacy of endoscopic sclerotherapy for esophageal varices.

To determine the diagnostic accuracy of computer tomography in the detection of venous collaterals surrounding the esophagus in patients with portal hypertension, preoperative computer tomography interpretations of these veins in 15 patients who were candidates for the Sugiura procedure for treatment of esophageal varices were correlated with those of the intraoperative assessment. Laparotomy revealed severe paraesophageal varices in five patients; four of them were found to have paraesophageal varices in computer tomography films. The sensitivity and specificity of computer tomography in diagnosing severe paraesophageal varices were 80% and 100%, respectively. A second assessment was performed in 59 additional patients with esophageal variceal hemorrhage to investigate the influence of paraesophageal varices on the efficacy of endoscopic sclerotherapy in the treatment of varices. The patients were divided into two groups: Group A included 17 patients with and group B 42 patients without paraesophageal varices on presclerotherapy computer tomography. All patients underwent elective sclerotherapy after being deemed hemodynamically stable. Patients in group A required more treatment sessions, more sclerosant and longer periods to obliterate varices completely than did group B patients. Eight patients in group A and six in group B (57% vs. 16%, p < 0.05) had variceal recurrence after obliteration during mean follow-ups of 20.8 and 19.9 mo, respectively. The mean time elapsed before variceal reappearance was shorter for group A than for group B (4.1 +/- 3.3 vs. 11.8 +/- 2.7 mo, p < 0.05). Among patients who developed new varices, five patients in group A and one in group B experienced repeat bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)