Magnetic resonance imaging for the evaluation of acute abdominal pain in pregnancy.

The investigation of acute abdominal pain in pregnancy is challenging. The use of ultrasound may be limited due to the patient's change in body habitus and computed tomography is not desirable due to fetal irradiation. Magnetic resonance imaging (MRI) has thus become increasingly popular in the evaluation of such patients, due to its lack of ionizing radiation, multiplanar capability and high contrast resolution. This review will detail the MRI technique required to image the pregnant abdomen and describe the MRI features of common causes of acute abdominal pain in pregnancy.

Elevated tumour marker: an indication for imaging?

INTRODUCTION: The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication. MATERIALS AND METHODS: Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of 'elevated tumour marker' in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated. RESULTS: Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41-91] y), were imaged to evaluate: 'elevated tumour marker'. They underwent 29 imaging studies (mean [+/-standard deviation (SD)] per patient = 1.2 [+/-0.4]), and had 42 elevated tumour marker serology tests (mean [+/-SD] per patient = 1.7 [+/-0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker. CONCLUSION: The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of 'elevated tumour marker'. 'Elevated tumour marker', in the absence of a known underlying malignancy, should not be considered an independent indication for imaging.

Improved graft survival in highly sensitized patients undergoing renal transplantation after the introduction of a clinically validated flow cytometry crossmatch.

BACKGROUND: Flow cytometric techniques are increasingly used in pretransplant crossmatching, although there remains debate regarding the clinical significance and predictive value of donor-specific antibodies detected by flow cytometry. At least some of the discrepancies between published studies may arise from differences in cutoffs used and lack of standardization of the test. METHODS: We selected cut-off values for pretransplant flow cytometric crossmatching (FCXM) based on the correlation of retrospective results with the occurrence of antibody-mediated rejection. The impact on long-term renal graft survival of prospective FCXM was determined by comparing graft survival between patients crossmatched with complement-dependent cytotoxicity (CDC) only with those prospectively crossmatched with both CDC and FCXM. RESULTS: Chosen cut-off values gave a positive predictive value of FCXM for antibody-mediated rejection of 83%, and a negative predictive value of 90%. After the introduction of prospective B- and T-cell crossmatching by flow cytometry in addition to CDC in our center, there was a significant improvement in renal graft survival in highly sensitized patients (P=0.017). Four-year graft survival in highly sensitized patients after the introduction of FCXM was 89%, which did not differ significantly from that seen in nonsensitized patients (93%; P=0.638). CONCLUSIONS: Our data demonstrate that prospective FCXM improves renal transplant outcome in highly sensitized patients, provided that cut-off values are carefully validated and results interpreted in the context of sensitization history and antibody screening results.

The relationship of clinical and inflammatory markers to outcome in stable patients with cystic fibrosis.

Decreased survival in patients with cystic fibrosis has been related to FEV1, BMI, and infection with Burkholderia cepacia complex (BCC). We have assessed the relationship of blood, sputum, and urine inflammatory markers to lung function, BMI, colonization with B cenocepacia (Bc), and patient survival. Thirty-nine stable cystic fibrosis (CF) patients (10 with Bc) were enrolled in a study to determine the effect of alpha-1-antitrypsin on airways inflammation. Pre-treatment measurements were used in this study. Demographics, sputum microbiology, heart rate, oxygen saturation, lung function were recorded. Blood samples were obtained for white blood count (WBC), C-Reactive Protein (CRP), and plasma neutrophil elastase/AAT complexes (pNEC). Neutrophil elastase (NE), neutrophil elastase/AAT complexes (sNEC), interleukin-8 (IL-8), TNF-receptor 1 (sTNFr), and myeloperoxidase (MPO) were measured in sputum and urinary desmosine concentration determined. Patients with Bc had significantly higher levels of pNEC, 332 +/- 91.4 ng/ml (mean +/- SEM) versus 106 +/- 18.2 ng/ml (P = 0.0005) and sNEC, 369 +/- 76.6 ng/ml versus 197 +/- 36.0 ng/ml compared to those who were not. Five deaths were reported at the end of 1 year, (four with Bc) (P = 0.011). Patients who subsequently died had significantly lower lung function FEV1, 1.2 +/- 0.2 L versus 2.0 +/- 0.1 L (P = 0.03) and FVC, 2 +/- 0.3 L versus 3.1 +/- 0.2 L (P = 0.01), compared to those that survived. There was significantly higher NE activity, 3.6 +/- 1.6 U/ml versus 1.5 +/- 0.6 U/ml (P = 0.03), pNEC, 274 +/- 99 ng/ml versus 142 +/- 30 ng/ml (P = 0.05), MPO, 163 +/- 62 mcg/ml versus 54 +/- 6.9 mcg/ml (P = 0.03), and urinary desmosines 108 +/- 19.9 pM/mg creatinine versus 51.1 +/- 3.3 pM/mg creatinine (P = 0.001), in those patients who subsequently died compared to those that survived. These data suggest there is increased neutrophil degranulation in patients infected with Bc and these patients have a poor outcome.

Safety and efficacy of recombinant alpha(1)-antitrypsin therapy in cystic fibrosis.

Neutrophil elastase (NE) is thought to be the most important protease which damages the cystic fibrosis (CF) lung. Attempts have been made to suppress this activity using the plasma-derived inhibitor, alpha(1)-antitrypsin (AAT). In this pilot study, the safety and efficacy of inhaled recombinant human AAT (rAAT) as a treatment for CF were investigated. Thirty-nine patients participated in a prospective, double-blinded, randomized, placebo-controlled phase II trial to examine the effect of rAAT (500, 250, and 125 mg) on sputum NE activity. Sputum myeloperoxidase (MPO), interleukin-8, tumor necrosis factor receptors, sputum and plasma NE/AAT complexes, and safety parameters were also measured. Subjects were randomized to receive nebulized treatment once a day for 4 weeks, followed by 2-4 weeks with no study treatment, and then a 2-week rechallenge phase. Trends toward a reduction in NE activity were observed in patients treated with 500 mg and 250 mg of rAAT compared to placebo. Sputum NE/AAT complex and MPO levels were lower on rAAT compared to placebo. No major adverse events and, in particular, no allergic reactions to rAAT were observed. Although significant differences between rAAT and placebo for sputum NE activity were not observed, some improvements were found for secondary efficacy variables. This study demonstrated that nebulized rAAT is safe and well-tolerated, but has a limited effect on NE activity and other markers of inflammation.

Accuracy of breath-hold magnetic resonance imaging in preoperative staging of organ-confined renal cell carcinoma.

PURPOSE: To determine the accuracy of breath-hold magnetic resonance (MR) imaging for preoperative staging of patients with organ-confined (stage I) renal cell carcinoma. MATERIALS AND METHODS: Preoperative MR examinations of 43 patients (50 lesions) who underwent nephrectomy were reviewed. The MR examination consisted entirely of breath-hold sequences, and images were retrospectively evaluated by 2 blinded radiologists. Reviewers independently evaluated each case for findings that could affect the radiologic staging, particularly those that distinguish between organ-confined (stage I) and non-organ-confined (>stage II) disease. Each reviewer assigned a stage, and results were correlated with findings at surgery and pathologic examination. RESULTS: The difference between both reviewers and pathologic findings in evaluating an intact renal capsule (stage I) was statistically significant (P < 0.05) and resulted in a statistically significant difference between radiologic and pathologic staging (Wilcoxon test, P < 0.05). The kappa test demonstrated moderate agreement between radiologic and pathologic staging (82% and 80% for reviewers 1 and 2, kappa = 0.54 and 0.80, respectively) and substantial agreement (90%, kappa = 0.80) between the 2 reviewers in assigning a radiologic stage. CONCLUSION: Breath-hold MR imaging has an accuracy ranging between 80% and 82% in staging patients with organ-confined renal cell carcinoma, with substantial (90%) agreement between readers.

Reproducibility of linear tumor measurements using PACS: comparison of caliper method with edge-tracing method.

The aim of this study was to evaluate inter- and intra-observer reproducibility when making electronic caliper linear tumor measurements on picture archiving and communications systems (PACS) and compare them with linear measurements obtained from circumferential tracing of tumor perimeter. Three radiologists measured 64 masses from 30 patients on body CT scans in two separate settings. Long axis and perpendicular short axis were measured using electronic calipers. The edge of each tumor was traced electronically and the long and short axes were calculated by computer software. The reproducibility of a measurement was evaluated by computing and comparing the absolute value of the mean difference between initial and subsequent measurements. The mean differences +/-95% confidence interval (CI) between two measurements of the long by short axis were 3.8+/-2.6x3.1+/-1.8 mm when the caliper method was used and 3.5+/-2.0x3.2+/-1.5 mm when the tumor tracing method was used. There was no statistically significant difference in individual intra-observer reproducibility of tumor axes measurements. Neither long- nor short-axis single-dimension measurements resulted in significantly greater or lesser intra-observer reproducibility. When comparing caliper and tracing measurements, the overall mean difference (3.42+/-1.8 vs 3.38+/-1.4 mm) was not statistically significant. There was close correlation between the individual measurements made by each observer whether these were made by electronic calipers and when these were calculated from electronic tracings (Pearson correlations between 0.79 and 0.949). Current PACS systems allow reproducible linear, long or short axis, tumor measurements. There is no significant difference in reproducibility of measurements whether these are made directly with electronic calipers or calculated from tumor edge tracings.

Plasmapheresis as rescue therapy in accelerated acute humoral rejection.

Accelerated acute humoral rejection (AHR) continues to occur in renal transplantation despite improved crossmatching, with potentially devastating consequences. Between 1 June 1998 and 31 December 2000, 440 renal transplants were performed in our center. AHR was diagnosed by the demonstration of typical pathological features on renal histology and positive direct immunofluorescence or detection of anti-HLA antibodies in serum. AHR developed in 20 (4.5%) of our renal transplant recipients, nine male and eleven female at an average of 16.3 days post transplantation. All of these patients had a negative current cytotoxic crossmatch prior to transplantation. The median serum creatinine at diagnosis was 5.96 mg/dL, and 83% of these individuals developed oliguric renal failure requiring dialysis after having initially attained good graft function (median of best serum creatinine before AHR was 2.64 mg/dL). The 18 recipients who had not infarcted their grafts at the time of diagnosis of AHR received plasmapheresis in conjunction with intensification of their immunosuppressive regimen. This regimen was successful in reversing AHR in 78% of those treated with apheresis. In the 14 responders, graft survival at 6 months was 100% and at 12 months was 91%. Median serum creatinine at 6 and 12 months was 1.26 and 1.33 mg/dL, respectively. Patients received an average of 8.1 plasma exchanges. However, responders received a significantly higher frequency of plasmapheresis (P =.0053), despite undergoing a similar number of exchanges overall. Plasmapheresis appears to be an effective modality for reversing AHR and maintaining graft function.

Do patients with primary sclerosing cholangitis have a greater frequency of pancreatic abnormalities at MRI than patients with other liver diseases?

PURPOSE: It has been proposed that there is an increased frequency of pancreatic abnormalities in patients with primary sclerosing cholangitis (PSC). Our purpose is to compare the frequency of pancreatic abnormalities detected at MRI in patients with PSC and to compare these findings with those found in a matched cohort with other liver diseases. METHOD: We identified 29 patients who had either a histologic or an endoscopic retrograde cholangiopancreatography diagnosis of PSC and 29 age- and gender-matched patients with liver disease without PSC who underwent MRI at 1.5 T. The protocol included breath-hold T1-weighted gradient echo, echo train, fast spin echo, T2-weighted images and dynamic gadolinium-enhanced MRI. Two blinded readers retrospectively evaluated the MR images for abnormalities of pancreatic size and morphology, T1 and T2 signal intensity, duct size and irregularities, arterial-phase contrast enhancement, focal pancreatic masses, cystic lesions, peripancreatic fluid/edema, ascites, and capsular-like rim surrounding the pancreas. RESULTS: The prevalence of pancreatic and peripancreatic abnormalities was 10 of 29 (35%) in PSC patients and 14 of 29 (48%) in control patients. MR findings included ascites (9 PSC, 12 controls), peripancreatic edema (7 PSC, 11 controls), atrophy (4 PSC, 3 control), increased T2 signal (3 PSC, 4 controls), cystic lesions (2 PSC, 3 controls), abnormal T1 signal (1 PSC, 2 controls), and dilated pancreatic ducts (3 PSC, 2 controls). Quantitative parameters were not significantly different between PSC patients and the control subjects with pancreatic findings. CONCLUSION: There is no significant difference in pancreatic abnormalities detected on MRI between patients with PSC and those with other liver diseases.

Phase I clinical trial of recombinant human endostatin administered as a short intravenous infusion repeated daily.

PURPOSE: To perform a phase I trial of recombinant human endostatin (rhEndostatin; EntreMed, Rockville, MD) given as a daily 20-minute intravenous (IV) injection in adult patients with refractory solid tumors. PATIENTS AND METHODS: The daily dose was increased from 15 to 240 mg/m(2) by a factor of 100% in cohorts of three patients. In the absence of dose-limiting toxicity, uninterrupted treatment was continued until the tumor burden increased by more than 50% from baseline. Correlative studies included dynamic contrast-enhanced magnetic resonance imaging of tumor blood flow, urinary vascular endothelial growth factor and basic fibroblast growth factor levels, rhEndostatin serum pharmacokinetics, and monitoring of circulating antibodies to rhEndostatin. RESULTS: There were no notable treatment related toxicities among 15 patients receiving a total of 50 monthly cycles of rhEndostatin. One patient with a pancreatic neuroendocrine tumor had a minor response and two patients showed disease stabilization. Linearity in the pharmacokinetics of rhEndostatin was indicated by dose-proportionate increases in the area under the curve for the first dose and the peak serum concentration at steady state. Daily systemic exposure to rhEndostatin in patients receiving 240 mg/m(2)/d was approximately 50% lower than that provided by the therapeutically optimal dose in preclinical studies. CONCLUSION: rhEndostatin administered as a 20-minute daily IV injection at doses up to 240 mg/m(2) showed no significant toxicities. Evidence of clinical benefit was observed in three patients. Due to high variability between the peak and trough serum concentrations associated with the repeated short IV infusion schedule, daily serum drug levels only briefly exceeded concentrations necessary for in vitro antiangiogenic effects.

Polymers of alpha(1)-antitrypsin are chemotactic for human neutrophils: a new paradigm for the pathogenesis of emphysema.

Plasma deficiency of alpha(1)-antitrypsin is most commonly due to the Z mutation ((342)Glu--> Lys) and is associated with early-onset panlobular emphysema. The lung disease in these patients is attributed to the relative deficiency of circulating alpha(1)-antitrypsin resulting in uncontrolled neutrophil-derived proteolytic activity. We have previously demonstrated that the local deficiency of Z alpha(1)-antitrypsin is exacerbated by the formation of polymers within the lung and now show that this polymerization not only inactivates alpha(1)-antitrypsin but also converts the molecule to a chemoattractant for human neutrophils. The chemotactic action of polymeric alpha(1)-antitrypsin was substantially greater than that seen with other conformers, was of similar magnitude to C5a, and was apparent over a range of physiologically relevant concentrations (EC(50) 0.0045 +/- 0.002 mg/ml). The biologic activity of polymeric alpha(1)-antitrypsin was confirmed by the demonstration that polymers, but not native alpha(1)-antitrypsin, induced neutrophil shape change and stimulated myeloperoxidase release and neutrophil adhesion. Polymeric alpha(1)-antitrypsin had no effect on basal or N-formyl-Met-Leu-Phe- stimulated superoxide anion release or constitutive apoptosis. The chemotactic properties of polymeric alpha(1)-antitrypsin may provide an explanation for the excessive neutrophils found in the lungs of Z alpha(1)-antitrypsin homozygotes and suggests a new paradigm for the pathogenesis of emphysema in these patients.

Outcome analysis of patients with acute pancreatitis by using an artificial neural network.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the ability of an artificial neural network (ANN) that uses radiologic and laboratory data to predict the outcome in patients with acute pancreatitis. MATERIALS AND METHODS: An ANN was constructed with data from 92 patients with acute pancreatitis who underwent computed tomography (CT). Input nodes included clinical, laboratory, and CT data. The ANN was trained and tested by using a round-robin technique, and the performance of the ANN was compared with that of linear discriminant analysis and Ranson and Balthazar grading systems by using receiver operating characteristic analysis. The length of hospital stay was used as an outcome measure. RESULTS: Hospital stay ranged from 0 to 45 days, with a mean of 8.4 days. The hospital stay was shorter than the mean for 62 patients and longer than the mean for 30. The 23 input features were reduced by using stepwise linear discriminant analysis, and an ANN was developed with the six most statistically significant parameters (blood pressure, extent of inflammation, fluid aspiration, serum creatinine level, serum calcium level, and the presence of concurrent severe illness). With these features, the ANN successfully predicted whether the patient would exceed the mean length of stay (Az = 0.83 +/- 0.05). Although the Az performance of the ANN was statistically significantly better than that of the Ranson (Az = 0.68 +/- 0.06, P < .02) and Balthazar (Az = 0.62 +/- 0.06, P < .003) grades, it was not significantly better than that of linear discriminant analysis (Az = 0.82 +/- 0.05, P = .53). CONCLUSION: An ANN may be useful for predicting outcome in patients with acute pancreatitis.

CT colonography: colonic distention improved by dual positioning but not intravenous glucagon.

The aim of this study was to determine whether intravenous (IV) glucagon and dual positioning administered prior to CT colonography enhances colonic distention. We assessed the effect of dual positioning and IV glucagon on colonic distention in 96 patients who underwent CT colonography examinations. The CT colonography was performed in both supine and prone positions. Seventy-four patients received glucagon (1 mg i.v.) immediately prior to CT scanning and 22 patients did not. The bowel was divided into ten segments and colonic distention was scored by two radiologists in the supine, prone, and combined supine/prone positions using a five-point scale: 1=collapsed; 2=poorly visualized; > or = 3=adequate distention; 4=entire segment visualized and well distended; 5=excellent distention). A combined segmental and overall supine/prone distention score was calculated based on the sum of the mean score for each position. There was no significant difference in the degree of colonic distention between patients who received glucagon and those who did not [supine/prone distention score (mean +/- SE): 3.63 +/- 0.2 vs 3.85 +/- 0.2; p=n.s.]. The degree of colonic distention was greater in the prone position in both the glucagon (3.87 +/- 0.2 vs 3.38 +/- 0.2; p<0.05) and non-glucagon groups (4.01 +/- 0.2 vs 3.69 +/- 0.2; p=N.S.) particularly in the proximal colon. There was almost perfect agreement between both radiologists in their scoring of colonic distention on a per-patient basis ( k=0.9; p<0.001). Of 1480 bowel segments, 1261 (85.2%) were adequately distended in the glucagon group compared with 370 of 440 bowel segments (84%) in the non-glucagon group ( p=n.s.) Colonic distention at CT colonography is improved by dual positioning but not by the administration of intravenous glucagon. While our results suggest that other smooth muscle relaxants, including butyl scopolamine, may only have a limited role in improving colonic distention in CT colonography, further studies are required.

Comparison of MR cholangiopancreatographic techniques with contrast-enhanced cholangiography in the evaluation of sclerosing cholangitis.

OBJECTIVE: The purpose of our study was to compare MR cholangiopancreatography and contrast-enhanced cholangiography in patients with sclerosing cholangitis. MATERIALS AND METHODS: Twenty patients with sclerosing cholangitis were evaluated on MR cholangiopancreatography using the single-shot fast spin-echo technique at 1.5 T. A group of 19 healthy volunteers underwent MR cholangiopancreatography as controls. Thick-slab (2-cm sections) coronal oblique and thin-slab (5-mm sections) interleaved straight coronal MR images were obtained. All patients with sclerosing cholangitis had an MR cholangiopancreatogram within 12 months of a contrast-enhanced cholangiogram (mean, 3.8 months). Seventy-five percent of patients had an MR cholangiopancreatogram within 3 months of the contrast-enhanced cholangiogram. The MR cholangiopancreatograms and contrast-enhanced cholangiograms were reviewed independently in a random fashion by two radiologists who were unaware of clinical history for the degree of ductal visualization and for the presence and location of strictures of the intrahepatic and extrahepatic bile ducts. All discrepancies were resolved by a consensus, and the contrast-enhanced cholangiograms were regarded as the gold standard. Statistically significant data were calculated using the signed rank test (p < 0.01), and agreement analysis was calculated using Cohen's kappa. RESULTS: All findings on MR cholangiopancreatograms in healthy subjects were interpreted as normal, and all findings on MR cholangiopancreatograms in patients with sclerosing cholangitis were interpreted as abnormal. When compared with the control group, scans of patients with sclerosing cholangitis usually showed good visualization (>50%) of the intrasegmental (86% vs 9%) and peripheral (67% vs 0%) intrahepatic ducts on thick-slab MR cholangiopancreatography. Thick-slab MR cholangiopancreatography showed good visualization in more ducts than contrast cholangiography (84% vs 70%; p = 0.10) and showed more strictured ducts than contrast cholangiography (47% vs 36%; p = 0.22). When comparing those ducts with good visualization on both MR cholangiopancreatography and contrast cholangiography, we found that disagreement occurred regarding 32% of ducts. Most of the discrepancies (60%) resulted when a stricture was noted on MR cholangiopancreatography but not on contrast-enhanced cholangiography. Good interobserver agreement (kappa > 0.4) was noted for detecting strictures of the extrahepatic, left hepatic, left medial, and right posterior ducts, with the greatest agreement for extrahepatic ductal strictures (kappa = 0.8). CONCLUSION: Thick-slab MR cholangiopancreatography is the best technique for depicting normal and strictured bile ducts and allows the differentiation of healthy patients from patients with sclerosing cholangitis. Although endoscopic retrograde cholangiopancreatography was considered the standard, MR cholangiopancreatography was superior for intrahepatic biliary ductal visualization. Therefore, this technique is of value in the diagnosis and follow-up of patients with sclerosing cholangitis.