Effect of modulators on 5-fluorouracil metabolite patterns in murine colon carcinoma determined by in vitro 19F nuclear magnetic resonance spectroscopy.

High-resolution 19F nuclear magnetic resonance spectroscopy at 7 T was used to study the effect of modulators on the metabolism of 5-fluorouracil (5-FUra, 115 mg/kg i.p.) in C38 murine colon tumors grown in C57BL/6 mice. Distinct 5-FUra metabolite patterns were found in perchloric acid extracts of these tumors after treatment. The 19F nuclear magnetic resonance spectra exhibited resonances representing 5-FUra, the catabolites alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro-beta-alanine, as well as four distinct fluoronucleotide anabolites. Using this model system the effect of several modulators on 5-FUra tumor metabolite patterns was investigated: methotrexate (300 mg/kg); alpha-interferon (10(5) IU/animal); N-(phosphonacetyl)-L-aspartate (100 and 250 mg/kg); and leucovorin (300 and 750 mg/kg). A significant increase in the anabolite:catabolite ratio was observed for the groups treated with 5-FUra in combination with the modulators methotrexate (n = 8), alpha-interferon (n = 7), and high-dose leucovorin (n = 14), but not for low-dose leucovorin (n = 7). Cotreatment with high-dose N-(phosphonacetyl)-L-aspartate (n = 8) resulted in a significant decrease in the anabolite: catabolite ratio compared to treatment with 5-FUra alone (n = 16). Possible correlations of metabolite profiles with therapy response are discussed.

Postprandial gallbladder motility during long term treatment with the long-acting somatostatin analog SMS 201-995 in acromegaly.

The effects on gallbladder motility of long term treatment with the somatostatin analog SMS 201-995 (SMS) were studied in five patients with acromegaly treated for 6-32 months with 200-300 micrograms SMS daily. SMS (100 micrograms) or placebo was injected sc 45 min before a standard breakfast. Gallbladder volume (ultrasonography), plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured until 120 min after the meal. SMS completely suppressed the postprandial gallbladder contraction, despite a blunted, though still statistically significant, increase in plasma CCK from 1.6 +/- 0.2 pmol/L to an average of 3.7 +/- 1.7 pmol/L (P less than 0.01). The postprandial plasma PP peak after placebo was replaced by a slight but statistically significant decrease after SMS (P less than 0.05). A statistically significant correlation between the plasma CCK values and corresponding gallbladder volumes was seen only after placebo injection, not in the SMS study. We conclude that during long term treatment of acromegalics with SMS, an injection of 100 micrograms, sc, completely abolishes gallbladder contraction for at least 2 h after a standard breakfast, despite blunted, but still significant, CCK release. The data suggest a decreased sensitivity of the gallbladder to endogenous CCK during long term treatment with SMS. Careful control of patients with respect to the formation of gallstones is recommended.

Effect of equimolar amounts of long-chain triglycerides and medium-chain triglycerides on plasma cholecystokinin and gallbladder contraction.

The present study was undertaken to compare the effects of equimolar amounts of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) on plasma cholecystokinin (CCK) concentrations and gallbladder contraction in man. On separate mornings and in random order six healthy volunteers ingested either 60 mmol LCT or 60 mmol MCT. Plasma CCK concentrations were measured by a sensitive and specific radioimmunoassay and gallbladder contraction by ultrasonography. Ingestion of LCT induced significant increases in plasma CCK from 2.8 +/- 0.5 to 6.5 +/- 0.7 pmol/l (p less than 0.005) and decreases in gallbladder volume from 33.4 +/- 5.9 to 13.2 +/- 4.2 cm3 (p less than 0.005). On the other hand, no significant changes in plasma CCK and gallbladder volume were found after MCT. Ingestion of MCT was followed by abdominal cramps and diarrhea, while LCT were without side effects. It is concluded that, in contrast to LCT, MCT do not induce CCK release and gallbladder contraction.

Detection and differentiation of diffuse liver disease by quantitative echography. A retrospective assessment.

RATIONALE AND OBJECTIVES: The detectability of diffuse liver diseases by quantitative echography was retrospectively investigated using scans of patients with known pathologic findings (n = 103) and of normal subjects (n = 129). The authors determined the best set of quantitative parameters for this task. METHODS: Quantitative echography was comprised of acoustospectrographic parameters (frequency dependence of attenuation and backscattering) and image texture parameters. The disease processes studied included: acute hepatitis, hepatitis/cirrhosis, alcoholic hepatitis/cirrhosis, primary biliary cirrhosis, and steatosis. RESULTS: Correct differentiation of these diseases ranged from 88% to 97%. Correlations between histologic grading and echographic parameters were poor. With only one exception, the differentiation between any two of the diseases could be made in 60% to 99% of cases. Different parameters better differentiated abnormal from normal scans than among diseases. CONCLUSIONS: The detection of diffuse liver diseases can be based on echographic parameters, related to a diffuse scattering model, whereas the differentiation among diseases needs additional parameters derived from a structural scattering model. Further studies are indicated to assess the prospective potential of the devised methods.

Preoperative and postoperative assessment of laparoscopic inguinal hernia repair by dynamic MRI.

RATIONALE AND OBJECTIVES: To determine the value of dynamic MRI for seroma detection, hernia recurrence, and mesh placement in patients after laparoscopic inguinal hernia repair. METHODS: Thirteen inguinal hernias in 10 consecutive patients were evaluated before and after surgery by using an MRI protocol consisting of coronal T1-weighted (fast field echo) and T2-weighted (turbo spin-echo) images and two sequences obtained during straining (turbo field echo gradient technique). All patients underwent a transabdominal preperitoneal laparoscopic inguinal hernia repair. MRI scans were reviewed for the presence of postoperative fluid collections, recurrent hernia, and mesh localization. RESULTS: In all patients, an inguinal hernia was identified on the preoperative MRI and was absent on the postoperative MRI. In all patients treated laparoscopically, the mesh and its position were clearly identified. Three small fluid collections were found on the postoperative MRI scans. CONCLUSIONS: Dynamic MRI can demonstrate small, postoperative fluid collections and a sufficient hernioplasty by showing the proper position of the mesh and the absence of a hernia.

Dynamic magnetic resonance imaging in the diagnosis of groin hernia.

RATIONALE AND OBJECTIVES: The authors determine the feasibility of dynamic magnetic resonance (MR) imaging in the diagnosis of groin hernia. METHODS: Ten volunteers and 10 patients with clinically evident and surgically proven herniations were evaluated using T1-, and T2-weighted sequences and two dynamic sequences. The visibility of anatomic structures that are crucial for the assessment and the differentiation of inguinofemoral herniations was evaluated. RESULTS: The inguinal rings could be identified in all subjects. The inferior epigastric vessels could be identified in 85%. In 10 patients, 11 hernias were found at MR imaging, whereas at surgery and physical examination 13 herniations were diagnosed (84.6%). The two hernias that were missed initially could be identified retrospectively on MR imaging. One volunteer showed a small bilateral inguinal hernia on MR imaging that could be confirmed on physical examination. CONCLUSIONS: The anatomic structures that are crucial for the assessment and the differentiation of inguinofemoral herniations can be identified prospectively with MR imaging.

Detection of groin hernia with physical examination, ultrasound, and MRI compared with laparoscopic findings.

OBJECTIVE: To determine the diagnostic accuracy of physical examination, ultrasound, and dynamic MRI in patients with inguinal hernia. METHODS: In 41 patients with clinically evident herniations, 82 groins were evaluated using a standard ultrasound and MRI protocol, the latter including T1- and T2-weighted sequences as well as two dynamic sequences. All ultrasound examinations and MRI scans were reviewed without knowledge of clinical findings. In all cases, correlation with findings at laparoscopic surgery was made. RESULTS: At surgery, 55 inguinal herniations were found. Physical examination revealed 42 herniations (one false-positive finding), whereas ultrasound made the diagnosis of a hernia in 56 cases (five false-positive and four false-negative findings). MRI diagnosed 53 herniations (one false-positive and three false-negative findings). Thus, sensitivity and specificity figures were 74.5% and 96.3% for physical examination, 92.7% and 81.5% for ultrasound, and 94.5% and 96.3% for MRI. CONCLUSIONS: In patients with clinically uncertain herniations, MRI is a valid diagnostic tool with a high positive predictive value.

The effect of caffeine on renal vein renin concentration in patients with renal arterial disease.

The aim of this study was to investigate whether caffeine stimulates selectively renal vein renin levels at the side of unilateral stenosis in patients with renovascular hypertension. In this study seven of the involved patients had renal arterial stenosis and four had no stenosis. Four of the seven patients with a stenosis had retrospectively-proven renovascular hypertension. Renal vein renin sampling was performed before and after intravenous administration of caffeine. Caffeine did not induce any consistent effect on plasma renin activity in the renal veins, either on the stenotic side or on the contralateral side in patients with renovascular hypertension. There were no consistent caffeine mediated changes in systemic plasma renin activity.

Magnetic resonance angiography has a high reliability in the detection of renal artery stenosis.

In this prospective study we examined the value of magnetic resonance angiography (MRA) in the imaging of the proximal renal arteries, with the main aim of detecting renal arterial stenosis, as compared with intraarterial digital subtraction angiography. The study was done among a group of 38 hypertensive patients seen in the outpatient department of the department of medicine of our university hospital. In all patients a magnetic resonance angiography and an intraarterial subtraction angiography of the renal arteries was made, and the outcomes of the investigations were compared. Clinical and biochemical data of the patients also were analyzed in relation to the presence or absence of a stenosis. In one patient, MRA resulted in technical failure because of unsuspected claustrophobia. Of the remaining 37 patients, 14 had renal artery stenosis. Of 12 patients in whom the stenoses were >50% of luminal surface on intraarterial digital subtraction angiography, eight were unilateral and four bilateral. All these stenoses were recognized by magnetic resonance angiography. There was also one false positive result by magnetic resonance. Thus, for the identification of stenoses >50%, magnetic resonance has a sensitivity of 100% and a specificity of 96%. Of the 12 accessory renal arteries seen on digital subtraction angiography, only three were identified by magnetic resonance angiography. We conclude that magnetic resonance angiography has great accuracy in depicting the main renal arteries and detecting clinically significant renal artery stenosis; however, the identification of accessory renal arteries is suboptimal and should be improved.

Plasma cholecystokinin levels and gallbladder volumes after proctocolectomy with ileal pouch-anal anastomosis.

BACKGROUND: The colon and rectum contain regulatory peptides in mucosal endocrine cells, which suggests a hormonal role. In animal studies colectomy leads to increased plasma levels of cholecystokinin. Little is known about the effects of proctocolectomy with ileal pouch-anal anastomosis on the release of cholecystokinin in human beings. Therefore we studied the effects of this procedure on fasting, postprandial, and bombesin-stimulated plasma cholecystokinin levels and gallbladder volumes. METHODS: Ten patients who had undergone proctocolectomy with ileal pouch-anal anastomosis and 12 healthy volunteers participated in the study. Fasting and postprandial plasma cholecystokinin levels and gallbladder volumes were studied for 3 hours at 15-minute intervals. In a second experiment plasma cholecystokinin levels were measured before and during intravenous administration of bombesin in six patients with ileal pouch and five healthy volunteers. RESULTS: Fasting plasma cholecystokinin levels were higher (p < 0.05) in patients with ileal pouch-anal anastomosis (2.6 +/- 0.3 pmol/L) compared with controls (1.7 +/- 0.2 pmol/L). Integrated postprandial plasma cholecystokinin levels were also distinctly higher (p < 0.01) in patients (978 +/- 126 pmol/L.180 min) than in controls (588 +/- 60 pmol/L.180 min). Mean fasting gallbladder volume was significantly (p < 0.01) decreased in patients with ileal pouch-anal anastomosis (18 +/- 2 ml) compared with controls (28 +/- 2 ml). Postprandial gallbladder emptying as measured by percentage change was similar in both groups. After infusion of bombesin, integrated plasma cholecystokinin responses were higher (p < 0.05) in patients (161 +/- 20 pmol/L.20 min) than in controls (90 +/- 12 pmol/L.20 min). CONCLUSIONS: Fasting, postprandial, and bombesin-stimulated plasma cholecystokinin levels are elevated in patients with ileal pouch-anal anastomosis compared with controls. Fasting gallbladder volume is decreased after ileal pouch-anal anastomosis. These findings suggest that the colon contains a factor that inhibits the release of cholecystokinin.

Pancreatic mass due to Strongyloides stercoralis infection: an unusual manifestation.

A 30-year-old man returning from a trip through India complained of epigastric pain, diarrhea, loss of weight, and jaundice. Stool examination was positive for Strongyloides stercoralis. On ultrasonographic investigation, intravenous cholangiography, and endoscopic retrograde cholangiopancreaticography, stenosis of the distal common bile duct and enlargement of the pancreatic head were observed. The patient was treated for the Strongyloides infection. The jaundice disappeared within days, the laboratory finding normalized, and the patient recovered rapidly. However, the ultrasonographic examination showed a complete recovery in the course of about 2 years. From this report we conclude that in patients with obstructive jaundice and Strongyloides stercoralis infection, serious abnormalities resembling pancreatic tumour or pancreatitis can be found on ultrasonographic and radiological investigations, and this should be considered in the differential diagnosis of pancreatic mass in patients living in or returning from endemic areas.

Pattern recognition of loss of early systolic peak by Doppler ultrasound has a low sensitivity for the detection of renal artery stenosis.

In a group of 57 hypertensive patients seen in the out-patient department, the authors did a prospective study to the value of pattern recognition of changes in early systolic peak by Doppler ultrasound (DU) in the examination of renal arteries, as compared with intra-arterial digital subtraction angiography. In five patients (8.7%) DU resulted in technical failure, in one because of the inability to hold breath long enough, in one because the Doppler signals from one part of the kidney were unclear and in three because overlying adipose tissue hindered the examination. Among the remaining 52 patients, 13 had unilateral and six bilateral stenoses greater than 50% of the luminal surface on angiography. By DU 10 patients with a stenosis were identified, one of which was a false positive result. Of the remaining nine, six patients had a unilateral stenosis and three a bilateral stenosis that was identified as unilateral by ultrasound. Therefore, none of the bilateral stenosis was identified as such by DU. Thus, for the detection of renal artery stenoses greater than 50% visual waveform analysis of DU signals has a sensitivity of 47% and a specificity of 97%. The conclusion is therefore that the DU procedure employed in this study has a limited value in the examination of the renal arteries of hypertensive patients with the aim to detect renal arterial stenosis.

Ultrasound attenuation and texture analysis of diffuse liver disease: methods and preliminary results.

A study was performed to find and test quantitative methods of analysing echographic signals for the differentiation of diffuse liver diseases. An on-line data acquisition system was used to acquire radiofrequency (RF) echo signals from volunteers and patients. Several methods to estimate the frequency-dependent attenuation coefficient were evaluated, in which a correction for the frequency and depth-dependent diffraction and focusing effects caused by the sound beam was applied. Using the estimated value of the attenuation coefficient the RF signals themselves were corrected to remove the depth dependencies caused by the sound beam and by the frequency-dependent attenuation. After this preprocessing the envelope of the corrected RF signals was calculated and B-mode images were reconstructed. The texture was analysed in the axial direction by first- and second-order statistical methods. The accuracy and precision of the attenuation methods were assessed by using computer simulated RF signals and RF data obtained from a tissue-mimicking phantom. The phantom measurements were also used to test the performance of the methods to correct for the depth dependencies. The echograms of 163 persons, both volunteers and patients suffering from a diffuse liver disease (cirrhosis, hepatitis, haemochromatosis), were recorded. The mutual correlations between the estimated parameters were used to preselect parameters contributing independent information, and which can subsequently be used in a discriminant analysis to differentiate between the various diseased conditions.

Variability of quantitative echographic parameters of the liver: intra- and interindividual spread, temporal- and age-related effects.

The values of acoustic and image texture parameters were estimated from liver scans of healthy subjects. The values were obtained after appropriate preprocessing of the radio frequency echograms by an on-line computerized system. The preprocessing comprised a correction for the Time Gain Compensation (TGC), the beam diffraction and the frequency dependent attenuation in the Region of Interest (ROI). The intra- and interindividual variability of the parameter values appeared to be of the same order of magnitude, but significantly larger than the variability assessed by measurements of a homogeneously scattering tissue mimicking phantom. Significant temporal effects were found for all the parameters, which consistently occurred during the morning. These results are discussed in relation to the circadian rhythm of the glycogen content and of the hepatic circulation. All the parameters appeared to be significantly correlated to age. The slope of the regression ranged from 3.6% per decade (attenuation coefficient) to 7.6% per decade (mean echo-level). A tentative explanation to these results is presented: the increased stiffness of hepatic vasculature with age.

Correlations between acoustic and texture parameters from RF and B-mode liver echograms.

Radio frequency (RF) echograms were acquired from human subjects without liver pathology (n = 126), who were in the range of 20 to 84 years of age. After appropriate correction for the equipment settings and performance characteristics, acoustospectrographic parameters were estimated. The data were corrected for the frequency-dependent attenuation and then software demodulated. Image texture parameters were calculated based on the assumption of a particular tissue model, and purely statistical parameters were also estimated. The data thus obtained from each subject were corrected for the age trend that was assessed in an earlier publication by the authors. A total of 18 parameters was considered and the correlations were analyzed. It is concluded that nine parameters could be identified which did not strongly correlate with each other. This conclusion is supported by analysis of correlation data from patients. In a companion paper, a discriminant analysis is reported, based on the selected parameters (nine) and applied to the differentiation between normals and various classes of diffuse liver disease.

Detection of diffuse liver disease by quantitative echography: dependence on a Priori choice of parameters.

Quantitative acoustic parameters and image texture parameters were used in a linear discriminant analysis. This analysis was applied to detect retrospectively the classes of diffuse liver disease against a population of normal livers. Three different sets of parameters were employed. The first set was selected by the authors, and the other two were taken from the literature. The area under the Receiver Operating Characteristic (ROC) (or percentage correct classification) obtained with the first set ranged from 88% to 97%, depending on the disease class. It is concluded that the first-order statistical parameters of the image texture (diffuse scattering model) together with the slope of the attenuation coefficient are the most important parameters. As an alternative to the texture parameters, the backscattering parameters (second set of parameters) also yielded a comparably high score. The texture analysis involving structural scattering (third set of parameters) produced a lower percentage of correct classification. The overall conclusion is that the methods devised might be used for prospective diagnosis.

Quantitative ultrasonic analysis of liver metastases.

The performance of five features of ultrasonic tissue characterization (UTC) of metastases in vivo in liver was investigated. We acquired serial radiofrequency data sets of 12 patients with metastases in the liver from adenocarcinoma of the colon. Parenchyma and metastases UTC features were estimated in semiautomatically segmented regions. Over 200 metastases were measured in patients and 43 dummy metastases in healthy volunteers. Two attenuation features could be estimated in only 15% of the metastases, and these were not different from those in parenchyma. The texture features signal-to-noise ratio (SNR) could not discriminate real from dummy metastases. Average backscatter intensity, b0, is an established discriminative echographic image feature. However, the metastases that were hypoechoic relative to surrounding parenchyma appeared to be isoechoic relative to normal liver parenchyma. They were visible because of an increased b0 in the surrounding liver parenchyma. Finally, we found an increased backscatter coefficient slope vs. frequency in hypoechoic metastases that may predict a deterioration of lesion contrast at higher transducer frequencies. We conclude that the backscatter coefficient slope can improve detection of metastases, and that b0 measured relative to normal liver parenchyma should be used to correctly correlate metastasis echography with histology.

Doppler ultrasound scanning in the detection of renal artery stenosis in hypertensive patients.

The diagnostic accuracy of Doppler ultrasound in the detection of renal arterial disease has been assessed in a prospective study of 61 hypertensive patients. The findings of Doppler ultrasound were compared with the results of renal angiography. In 15 patients (24.5%) no accurate Doppler signs could be obtained and the Doppler ultrasound examination was considered a technical failure. Of the remaining 46 patients, 24 had renal artery stenosis. Nine of the stenoses were not detected by Doppler ultrasound and in three patients a false positive diagnosis of renal artery stenosis was made. The sensitivity of Doppler ultrasound was 62.5%, the specificity 86.4% and the overall diagnostic accuracy was 73.9%. By comparing the 15 patients in whom Doppler ultrasound failed with the 46 in whom it was successful, age appeared to be higher and creatinine clearance lower in the failure group. By comparing the 34 patients with true positive and true negative results with the 12 patients with false results, no significant differences were found. In a multivariate analysis, higher age showed a significant relation to failure of Doppler ultrasound. Doppler ultrasound has limited value in the screening of hypertensive patients for renal artery stenosis.

Ischaemic colitis associated with carcinoma of the colon.

In a retrospective study of one hundred and seventy patients with ischaemic colitis, we found eight patients with partially obstructive carcinoma of the colon located distally, seven located in the sigmoid and one in the splenic flexure. The frequency of this association (1-4.7% in the literature and 5.3% in our series) requires careful examination by radiologist and surgeon. The radiologist should be alert to the association of ischaemic damage proximal to an obstructive colorectal cancer. The surgeon must examine any colonic segment removed for carcinoma in order to exclude an ischaemic process in the area of the anastomosis and prevent leakage at the anastomosis or stricture formation.

A pheochromocytoma of the urinary bladder.

This case report describes a patient with a pheochromocytoma of the urinary bladder. The patient demonstrated an excessive increase of blood pressure and plasma catecholamines immediately after micturition. Ultrasound and CT-scanning confirmed the localisation of the tumour in the urinary bladder.