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ObjectiveWe aimed to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE).MethodsWe conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16–75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomised to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6).ResultsOf 66 patients randomised, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4±18.1 with mepolizumab and 8.3±18.0 with placebo (p=0.14). Peak eosinophil counts decreased more with mepolizumab (113±77 to 36±43) than placebo (146±94 to 160±133) (p<0.001). With mepolizumab, 42% and 34% achieved histological responses of <15 and ≤6 eos/hpf compared with 3% and 3% with placebo (p<0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3±18.1 points for mepo/mepo and 18.6±19.2 for pbo/mepo (p=0.85). The most common adverse events were injection-site reactions.ConclusionsMepolizumab did not achieve the primary endpoint of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement.Trial registration numberNCT03656380.

ObjectiveAlcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking.DesignTwo large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed.ResultsAge and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism.ConclusionsDespite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR−/−T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4+T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T (pTreg) cells in the colon of recipients transplanted with AhR−/−T cells 14 days after transplant. Blockade of AhR using a clinically available AhR antagonist greatly enhanced the in vitro generation of inducible Treg(iTreg) cells from naïve CD4+human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR−/− T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4+ T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T (pTreg) cells in the colon of recipients transplanted with AhR−/− T cells 14 days after transplant. Blockade of AhR using a clinically available AhR antagonist greatly enhanced the in vitro generation of inducible Treg (iTreg) cells from naïve CD4+ human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD.

Objectives:Esophageal dilation is commonly performed in eosinophilic esophagitis (EoE), but there are few long-term data. The aims of this study were to assess the safety and long-term efficacy of esophageal dilation in a large cohort of EoE cases, and to determine the frequency and predictors of requiring multiple dilations.Methods:We conducted a retrospective cohort study in the University of North Carolina EoE Clinicopathological Database from 2002 to 2014. Included subjects met consensus diagnostic criteria for EoE. Clinical, endoscopic, and histologic features were extracted, as were dilation characteristics (dilator type, change in esophageal caliber, and total number of dilations) and complications. Patients with EoE who had undergone dilation were compared with those who did not and also stratified by whether they required single or multiple dilations.Results:Of 509 EoE patients, 164 were dilated a total of 486 times. Those who underwent dilation had a longer duration of symptoms before diagnosis (11.1 vs. 5.4 years, P<0.001). Ninety-five patients (58%) required >1 dilation (417 dilations total, mean of 4.4±4.3 per patient). The only predictor of requiring multiple dilations was a smaller baseline esophageal diameter. Dilation was tolerated well, with no major bleeds, perforations, or deaths. The overall complication rate was 5%, primarily due to post-procedural pain. Of 164 individuals dilated, a majority (58% or 95/164) required a second dilation. Of these individuals, 75% required repeat dilation within 1 year.Conclusions:Dilation in EoE is well-tolerated, with a very low risk of serious complications. Patients with long-standing symptoms before diagnosis are likely to require dilation. More than half of those dilated will require multiple dilations, often needing a second procedure within 1 year. These findings can be used to counsel patients with fibrostenotic complications of EoE.

The variability of eosinophilic infiltrates in eosinophilic esophagitis is not well described. This study aimed to determine the distribution of esophageal eosinophilia and the utility of histologic cut-points for eosinophilic esophagitis diagnosis in subjects undergoing endoscopy. We performed a prospective study of adults undergoing outpatient endoscopy. Research protocol esophageal biopsies were obtained from all subjects. Incident cases of eosinophilic esophagitis were diagnosed per consensus guidelines. Biopsies were interpreted following a validated protocol, and maximum eosinophil counts (eosinophils per high-power field; eos/hpf) were determined. Histologic analyses were performed on a per-patient, per-biopsy, and per-hpf basis. There were 213 patients, yielding 923 esophageal biopsies with 4588 hpfs. Overall, 48 patients (23%), 165 biopsy fragments (18%), and 449 hpfs (10%) had ≥15 eos/hpf; most subjects had no or low levels of eosinophils. In the eosinophilic esophagitis cases, 119 biopsy fragments (63%) and 332 hpfs (36%) had ≥15 eos/hpf. There was a mean 104-fold difference between the lowest and highest hpf eosinophil count for the eosinophilic esophagitis patients; 85% of the biopsies from eosinophilic esophagitis cases also had at least one hpf with <15 eos/hpf. The cut-point of 15 eos/hpf had a sensitivity of 100% and a specificity of 96% for diagnosis of eosinophilic esophagitis. In conclusion, most patients have little to no esophageal eosinophilia. In patients with eosinophilic esophagitis, there was marked variability in the eosinophil counts by biopsy and by hpf within a given biopsy. Additionally, the 15 eos/hpf cut-point was highly sensitive and specific for eosinophilic esophagitis. Multiple esophageal biopsies from different locations should be obtained to optimize eosinophilic esophagitis diagnosis.

The variability of eosinophilic infiltrates in eosinophilic esophagitis is not well described. This study aimed to determine the distribution of esophageal eosinophilia and the utility of histologic cut-points for eosinophilic esophagitis diagnosis in subjects undergoing endoscopy. We performed a prospective study of adults undergoing outpatient endoscopy. Research protocol esophageal biopsies were obtained from all subjects. Incident cases of eosinophilic esophagitis were diagnosed per consensus guidelines. Biopsies were interpreted following a validated protocol, and maximum eosinophil counts (eosinophils per high-power field; eos/hpf) were determined. Histologic analyses were performed on a per-patient, per-biopsy, and per-hpf basis. There were 213 patients, yielding 923 esophageal biopsies with 4588 hpfs. Overall, 48 patients (23%), 165 biopsy fragments (18%), and 449 hpfs (10%) had ≥15 eos/hpf; most subjects had no or low levels of eosinophils. In the eosinophilic esophagitis cases, 119 biopsy fragments (63%) and 332 hpfs (36%) had ≥15 eos/hpf. There was a mean 104-fold difference between the lowest and highest hpf eosinophil count for the eosinophilic esophagitis patients; 85% of the biopsies from eosinophilic esophagitis cases also had at least one hpf with <15 eos/hpf. The cut-point of 15 eos/hpf had a sensitivity of 100% and a specificity of 96% for diagnosis of eosinophilic esophagitis. In conclusion, most patients have little to no esophageal eosinophilia. In patients with eosinophilic esophagitis, there was marked variability in the eosinophil counts by biopsy and by hpf within a given biopsy. Additionally, the 15 eos/hpf cut-point was highly sensitive and specific for eosinophilic esophagitis. Multiple esophageal biopsies from different locations should be obtained to optimize eosinophilic esophagitis diagnosis.

In 1996, the Association of Directors of Anatomic and Surgical Pathology (ADASP) published recommendations for colon carcinoma reporting. Since this publication, no study has evaluated physician practice in relation to these recommendations. The objectives of the current study were to describe pathology reporting for colon carcinoma, evaluate potential variations in reporting, and identify areas for improvement. Data were obtained from a population-based study of incident colon carcinoma in 33 counties in North Carolina between 1997 and 2000. All subjects with surgically resected colon carcinoma of tumor stage T2–T4 with available surgical pathology reports were eligible for inclusion in the current analysis. The authors reviewed pathology reports for adherence to recommendations of the ADASP. Four hundred thirty-eight pathology reports were included for analysis. Adherence to ADASP recommendations was &lt; 90% for descriptions of how specimen was received (68%), how specimen was identified (71%), macroscopic depth of penetration (82%), appearance of serosa adjacent to tumor (50%), and status of residual bowel (73%). All other criteria were reported in > 90% of patients. Teaching hospital and contract pathology laboratories had greater adherence to recommendations, compared with community hospital laboratories. Hospitals with the highest colon carcinoma case volume demonstrated greater adherence to recommendations, compared with low-volume hospitals. Pathology reports were effective in communicating most pertinent findings from surgically resected colon carcinoma specimens. Omissions of some critical characteristics did occur, however, and significant variability in reporting existed based on laboratory affiliation and hospital case volume. Cancer 2004. © 2004 American Cancer Society.

Background & Aims:Observational studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal neoplasia. The mechanism of this effect could be via modification of apoptotic activity in colonic mucosa. We examined grossly normal rectal mucosa in patients with adenomas and adenoma-free controls to assess the associations between NSAID use, adenomatous polyps, and apoptosis. Methods:Study participants were drawn from consecutive patients who underwent colonoscopy between August, 1998, and February, 2000. Biopsy specimens were taken from normal-appearing rectal mucosa 10 cm from the anal verge. Apoptosis was scored from coded, H&E-stained sections using morphologic methods. Proliferation was scored using whole crypt mitotic counts. Univariate and multivariate regression analyses were conducted to estimate crude and adjusted odds ratios (ORs). Results:There were 226 patients with adenomas and 493 adenoma-free controls. After adjusting for sex, age, race, and body mass index (BMI), individuals in the highest tertile of regular NSAID use were substantially less likely to have adenomas (OR 0.4; 95% CI: 0.2–0.7) compared with occasional or nonusers. Similarly, compared with the lowest tertile, persons in the highest tertile of rectal mucosal apoptotic activity were much less likely to have adenomas (OR 0.12; 95% CI: 0.07–0.20). NSAID use and apoptotic activity were not correlated (r= 0.10). Mucosal proliferation was not related to adenomas or NSAID use. Conclusions:Our observations suggest that NSAID use and higher levels of mucosal apoptosis are independently associated with a lower prevalence of adenomas. The study shows a strong field effect for apoptosis.

The purpose of this study was to evaluate the spectrum of appearances of gastrointestinal carcinoid tumors at magnetic resonance imaging (MRI) and to elucidate patterns of appearances of carcinoid liver metastases on precontrast and postgadolinium images. The MR examinations of 29 patients (11 men, 18 women; age range, 33–87 years) with histologically confirmed gastrointestinal carcinoid tumors, representing our complete 9.5 years of experience with this entity, were retrospectively reviewed. Twelve patients had MR examinations prior to resection or biopsy of the primary tumor (preoperative group); 17 patients were imaged postsurgically (postoperative group). All MR studies were performed at 1.5 T and comprised T1‐weighted spoiled gradient echo (SGE), T2‐weighted fat‐suppressed turbo spin echo, HASTE, and serial postgadolinium T1‐weighted SGE sequences without and with fat suppression. Morphology, signal intensity, and contrast enhancement of primary tumors and of metastases to the mesentery, peritoneum, and liver were evaluated. Primary tumors were visualized in 8 of 12 patients and best demonstrated on postgadolinium T1‐weighted fat‐suppressed images. The appearance of primary tumors was a nodular mass originating from the bowel wall (4 of 12 patients) or regional uniform bowel wall thickening (4 of 12 patients) with moderate intense enhancement on postgadolinium images. In 4 of 12 patients the primary tumor was prospectively not seen. Mesenteric metastases, seen in eight patients, presented as nodular masses and were associated with mesenteric stranding in seven patients. A total of 156 liver metastases were evaluated in 16 patients. On precontrast T1‐ and T2‐weighted images, 117 metastases (75%) were hypointense and hyperintense, respectively. A total of 146 metastases (94%) were hypervascular, showing moderate intense enhancement during the hepatic arterial phase, and 9 metastases (6%) were hypovascular. Twenty‐three metastases (15%) were visible only on immediate postgadolinium images. MRI is able to demonstrate findings in carcinoid tumors, including the primary tumor, mesenteric metastases, and liver metastases. Liver metastases are commonly hypervascular and may be demonstrable only on immediate postgadolinium images. J. Magn. Reson. Imaging 2001;14:261–269. © 2001 Wiley‐Liss, Inc.

The purposes of our study were to describe the early and late enhancement patterns of the liver on gadolinium‐enhanced dynamic magnetic resonance (MR) images in patients with chronic hepatitis and to correlate these findings with histopathology. Patients were entered into the study based on the presence of chronic hepatitis, imaging evaluation with MR imaging (MRI), including early and late postgadolinium images, and histopathologic correlation. Early and late dynamic postgadolinium MR images of 29 consecutive patients with a pathologically proven diagnosis of chronic hepatitis were retrospectively evaluated for the presence of three types of enhancement, i.e., homogeneous, linear, and patchy. Correlation was made between the enhancement patterns on MR images and blinded retrospective interpretation of the histopathologic specimens, which were obtained within 3 months of the MR examination. Of the 29 patients, 16 (55.2%) patients showed patchy enhancement on the early gadolinium‐enhanced MR images. In 11 (68.8%) of these 16 patients, histopathology demonstrated numerous macrophages, variable hepatocyte necrosis, and increased steatosis. The remaining 13 (44.8%) patients showed homogeneous enhancement on the early gadolinium‐enhanced MR images. In 11 (84.6%) of these 13 patients, histopathology demonstrated few or no macrophages, little or no hepatocellular necrosis, and little or no steatosis. The correlation between patchy enhancement and acute liver inflammation was significant (P= 0.005). On the late gadolinium‐enhanced MR images, 20 (69.0%) of 29 patients showed prominent linear enhancement. In 19 (95.0%) of these 20 patients, histopathology revealed hepatic fibrosis. We concluded that in patients with chronic hepatitis, the presence of early patchy enhancement indicates either concurrent or recent hepatocellular damage, whereas the presence of late linear enhancement indicates the presence of fibrosis, with a high degree of correlation with histopathologic findings. J. Magn. Reson. Imaging 2001;13:385–391. © 2001 Wiley‐Liss, Inc.

We reviewed our 8.5 year experience with magnetic resonance imaging (MRI) in the demonstration of neuroendocrine tumors of the pancreas using precontrast fat-suppressed T1-weighted, fat-suppressed T2-weighted, and serial post-gadolinium T1-weighted images, to describe the spectrum of appearances of these tumors. All MR examinations of patients with histogically proven neuroendocrine tumors were retrospectively reviewed. Histological type, tumor location, tumor diameter, signal intensity on precontrast images, enhancement patterns, and presence and appearance of metastases were determined. Twenty-two patients had histologically proved neuroendocrine tumors detected by MRI over the 8.5 year period. Histological types were gastrinoma (n = 8), insulinoma (n = 3), glucagonoma (n = 2), somatostatinoma (n = 1), VIPoma (n = 1), ACTHoma (n = 1), carcinoid (n = 1), and five untyped tumors. Primary tumors ranged in diameter from 1 to 6.2 cm. There was one histopathology-proven false-positive neuroendocrine tumor. The positive predictive value for MRI in the detection of these tumors was 96%. The most common appearance on precontrast images was low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, which was observed in tumors in 18 of 22 patients. Moderate or intense early enhancement of all or portions of the primary tumors was observed in tumors in 19 of 22 patients either as uniform homogeneous, ring, or diffuse heterogeneous enhancement. Enhancement was minimal on these images in the other three patients. Gastrinomas enhanced in a ring pattern in 7 of 8 patients whereas the majority (9 of 11 patients) of noninsulinoma-nongastrinoma and untyped tumors enhanced in a diffuse heterogeneous fashion. Liver metastases were present in 13/22 patients including 3/8 with gastrinoma and 9/11 with noninsulinoma-nongastrinoma tumors. Most neuroendocrine tumors of the pancreas are low signal intensity on fat-suppressed T1-weighted images and moderately high in signal intensity on fat-suppressed T2-weighted images, although variations do exist. Tumors most often enhance in an early moderately intense fashion. Gastrinomas are often different in appearance than other neuroendocrine tumors in that they usually enhance in a ring fashion whereas nongastrinoma-noninsulinoma tumors usually enhance in a heterogeneous fashion. J. Magn. Reson. Imaging 2000;11:141–148. © 2000 Wiley-Liss, Inc.

We reviewed our 8.5 year experience with magnetic resonance imaging (MRI) in the demonstration of neuroendocrine tumors of the pancreas using precontrast fat‐suppressed T1‐weighted, fat‐suppressed T2‐weighted, and serial post‐gadolinium T1‐weighted images, to describe the spectrum of appearances of these tumors. All MR examinations of patients with histogically proven neuroendocrine tumors were retrospectively reviewed. Histological type, tumor location, tumor diameter, signal intensity on precontrast images, enhancement patterns, and presence and appearance of metastases were determined. Twenty‐two patients had histologically proved neuroendocrine tumors detected by MRI over the 8.5 year period. Histological types were gastrinoma (n= 8), insulinoma (n= 3), glucagonoma (n= 2), somatostatinoma (n= 1), VIPoma (n= 1), ACTHoma (n= 1), carcinoid (n= 1), and five untyped tumors. Primary tumors ranged in diameter from 1 to 6.2 cm. There was one histopathology‐proven false‐positive neuroendocrine tumor. The positive predictive value for MRI in the detection of these tumors was 96%. The most common appearance on precontrast images was low signal intensity on T1‐weighted images and high signal intensity on T2‐weighted images, which was observed in tumors in 18 of 22 patients. Moderate or intense early enhancement of all or portions of the primary tumors was observed in tumors in 19 of 22 patients either as uniform homogeneous, ring, or diffuse heterogeneous enhancement. Enhancement was minimal on these images in the other three patients. Gastrinomas enhanced in a ring pattern in 7 of 8 patients whereas the majority (9 of 11 patients) of noninsulinoma‐nongastrinoma and untyped tumors enhanced in a diffuse heterogeneous fashion. Liver metastases were present in 13/22 patients including 3/8 with gastrinoma and 9/11 with noninsulinoma‐nongastrinoma tumors. Most neuroendocrine tumors of the pancreas are low signal intensity on fat‐suppressed T1‐weighted images and moderately high in signal intensity on fat‐suppressed T2‐weighted images, although variations do exist. Tumors most often enhance in an early moderately intense fashion. Gastrinomas are often different in appearance than other neuroendocrine tumors in that they usually enhance in a ring fashion whereas nongastrinoma‐noninsulinoma tumors usually enhance in a heterogeneous fashion. J. Magn. Reson. Imaging 2000;11:141–148. © 2000 Wiley‐Liss, Inc.

The purpose of this study was to describe the magnetic resonance (MR) imaging features of biliary hamartomas on T1- and T2-weighted and gadolinium-enhanced sequences, and to correlate these findings with histopathology. MR imaging findings in four patients with pathologically proved biliary hamartomas are described. In all patients, MR imaging sequences, including T1- and T2-weighted and early and late gadolinium-enhanced images, were retrospectively evaluated for the size, morphology, signal intensity, and enhancement pattern of the lesions. Correlation was made between the MR imaging findings and histopathology. Biliary hamartomas ranged in diameter from 0.5 to 1.5 cm. Lesions were solitary in one patient and numerous in three patients. In all patients, the lesions were low signal on T1-weighted images and high signal and well-defined on T2-weighted images and demonstrated thin rim enhancement on early post-gadolinium images that persisted on late post-gadolinium images. No appreciable central enhancement of the lesions was observed. At histopathology, the lesions were composed of cystic spaces and fibrous stroma. Lesions showed compressed liver parenchyma surrounding the lesions (three cases) and inflammatory cell infiltrate (one case), which correlated with the rim enhancement on the gadolinium-enhanced MR images. Most of the biliary hamartomas in our small series were less than 1 cm in diameter and of high signal intensity on T2-weighted images, and had a thin rim of enhancement on early and late post-gadolinium images. The imaging features were explainable by the underlying histopathology. In patients with known malignancy, caution should be exercised not to misinterpret these lesions as metastases due to the presence of thin rim enhancement. J. Magn. Reson Imaging 1999;10:196–201, 1999. © 1999 Wiley-Liss, Inc.

The purpose of this study was to describe the magnetic resonance (MR) imaging features of biliary hamartomas on T1‐ and T2‐weighted and gadolinium‐enhanced sequences, and to correlate these findings with histopathology. MR imaging findings in four patients with pathologically proved biliary hamartomas are described. In all patients, MR imaging sequences, including T1‐ and T2‐weighted and early and late gadolinium‐enhanced images, were retrospectively evaluated for the size, morphology, signal intensity, and enhancement pattern of the lesions. Correlation was made between the MR imaging findings and histopathology. Biliary hamartomas ranged in diameter from 0.5 to 1.5 cm. Lesions were solitary in one patient and numerous in three patients. In all patients, the lesions were low signal on T1‐weighted images and high signal and well‐defined on T2‐weighted images and demonstrated thin rim enhancement on early post‐gadolinium images that persisted on late post‐gadolinium images. No appreciable central enhancement of the lesions was observed. At histopathology, the lesions were composed of cystic spaces and fibrous stroma. Lesions showed compressed liver parenchyma surrounding the lesions (three cases) and inflammatory cell infiltrate (one case), which correlated with the rim enhancement on the gadolinium‐enhanced MR images. Most of the biliary hamartomas in our small series were less than 1 cm in diameter and of high signal intensity on T2‐weighted images, and had a thin rim of enhancement on early and late post‐gadolinium images. The imaging features were explainable by the underlying histopathology. In patients with known malignancy, caution should be exercised not to misinterpret these lesions as metastases due to the presence of thin rim enhancement. J. Magn. Reson Imaging 1999;10:196–201, 1999. © 1999 Wiley‐Liss, Inc.

Background:The present study was designed to further assess the reported association between cigarette smoking, alcohol, and colorectal adenomas. Methods:A number of environmental and life-style risk factors were examined in 236 patients with histologically proven adenomas and 409 controls with no adenomas. Results:Age, sex, race, and indication for procedure were similar in cases and controls. Those who had ever smoked were not at increased risk for adenomas compared with those who had never smoked. Years of smoking, cigarettes per day, and total packyears showed no dose-response effect. Results for men and women were similar. Alcohol was a significant risk factor for men but not for women. Men in the highest quartile of daily caloric intake from alcohol were more than four times more likely than nondrinkers to develop adenomas, with a statistically significant trend in risk from the lowest to the highest quartile. These findings persisted after controlling for other potential risk factors for adenomas. The risk for colon and rectal polyps were similar. Men in the highest tertile of beer consumption were nearly six times more likely to develop adenomas than nondrinkers. Conclusions:Beer drinking is a risk factor for colorectal adenomas in this population.

This study compares liver lesion detection, characterization, and effect on patient management between single‐phase spiral CT and MRI using spoiled gradient echo (SGE), T2‐weighted fat‐suppressed spin echo, and serial post gadolinium SGE. All patients with suspected liver lesions who underwent spiral CT and MRI within a 1‐month period between January 1993 and September 1996 were included in the study. Spiral CT and MRI were interpreted prospectively in a blinded fashion by separate individual experienced investigators, and lesion detection and characterization were determined. Confirmation was obtained by surgery (6 patients), biopsy (18 patients), imaging follow‐up (36 patients), or combined reading of all imaging studies and clinical follow‐up (29 patients). Effect on patient management was determined by combined chart review and interview of the patients' physicians and by retrospective clinical assessment performed by a surgical oncologist and medical oncologist separately. Eighty‐nine patients were included in the study. Regarding true positive lesion detection, 295 and 519 lesions were detected on spiral CT and MR images, respectively, which was significantly different on a patient‐by‐patient basis (P< .001). More lesions were detected on MR than on spiral CT in 44 of 89 patients (49.4%), and 11 of these 44 patients had lesions shown on MRI in whom no lesions were apparent on CT images. No patients had true positive lesions shown on spiral CT that were not shown on MRI. Regarding lesion characterization, 129 and 466 lesions were characterized on spiral CT and MRI images, respectively, which was significantly different on a patient‐by‐patient basis (P< .001). More lesions were characterized on MR than CT images in 67 patients (75.3%). Regarding effect on patient management, chart review with physician interview demonstrated that findings on MRI provided information that altered patient management as compared with findings on spiral CT in 57 patients. Retrospective clinical evaluation by the surgical and medical oncologist showed that MRI was considered to have a greater effect on patient management than spiral CT in 58 and 55 patients, respectively. Comparing current MRI technique to single‐phase spiral CT, MRI detected more lesions in 49.4% and characterized more lesions in 75.3% of patients investigated for focal liver disease. MRI had a greater effect on patient management in each of the three methods than singlephase spiral CT in more than 61% of patients.

This study describes the occurrence of hemorrhage in renal cancer in patients with chronic renal insufficiency as shown on MR images. Thirteen consecutive patients with chronic renal insufficiency who had his tologically proven renal cancer and underwent MRI at 1.5 T were entered in the study. MR examinations included spoiled gradient echo (SGE) and T1‐weighted fat‐suppressed imaging pre‐ and postgadolinium administration. All renal cancers were well shown on MR images and were most clearly depicted on postgadolinium T1‐weighted fat‐suppressed images. Tumors in 12 of 13 patients had regions of high signal intensity on precontrast T1‐weighted images. Histology demonstrated intratumoral hemorrhage in all 12 of these patients. Four hemorrhagic tumors were largely cystic on imaging studies. One of these cancers altered in appearance from largely cystic with extensive hemorrhage to largely solid with substantial enhancement after a 2.5‐year interval. Renal cancers demonstrated minimal enhancement (11 patients) on early postgadolinium images and were minimally enhanced on delayed images in 10 of 13 tumors. Two renal cancers demonstrated intense enhancement. Renal cancers are well shown on MR images in patients with chronic renal insufficiency. Because of the common occurrence of hemorrhage into renal cancers in patients with renal insufficiency, caution should be exercised when evaluating hemorrhagic cystic lesions in these patients.

PurposeCalciphylaxis is a rare devastating condition of cutaneous necrosis resulting from calcification of small blood vessels in patients with end stage renal failure and secondary hyperparathyroidism. We describe 5 patients with penile calciphylaxis at a single institution.Materials and MethodsFrom 1992 to 1996, 5 patients had penile calciphylaxis. The charts of these patients were reviewed to determine the nature of the lesions, association with hyperparathyroidism and treatment outcomes.ResultsAll 5 patients had chronic renal failure, secondary hyperparathyroidism and painful necrotic lesions at multiple sites. Radiographs showed stippled calcification of small vessels, which was confirmed histologically. Three patients had undergone parathyroidectomy with a significant decrease in mean calcium x phosphorus ion products from 86.01 to 45.37 mg.2/dl.2 (p <0.001), and in 1 calciphylaxis resolved postoperatively. The penile lesions were treated with debridement and aggressive wound care.ConclusionsThe increase in the number of patients with chronic renal failure on dialysis may make penile calciphylaxis more prevalent in the future. Lowering of serum calcium and phosphorus levels, and debridement of these necrotic lesions help to diminish this aggressively destructive process.

This report describes the sonographic and MR appearances of acute Budd-Chiari syndrome (BCS) in a 30-year-old woman. Current imaging techniques including duplex Doppler sonography and dynamic gadolinium-enhanced MRI were employed, and direct histopathologic correlation was made. Duplex Doppler sonography revealed a heterogeneous enlarged liver, no flow in the left and middle hepatic veins, and only trace abnormal flow in the distal-most right hepatic vein. Dynamic serial gadolinium-enhanced, spoiled gradient echo imaging demonstrated early homogeneous enhancement of an enlarged caudate lobe, as well as heterogeneously decreased enhancement of the remainder of the hepatic parenchyma. This differential enhancement pattern persisted on delayed imaging. Patent hepatic veins were not demonstrated on any sequence. Associated findings included hepatomegaly, ascites, and patent portal vasculature. These imaging findings were interpreted as consistent with acute BCS. Within 10 days, the patient underwent orthotopic liver transplantation. Histopathology demonstrated hepatic necrosis and hepatic venous thrombosis consistent with acute BCS.

= 6 for each size). The dilated PTFE segments were evaluated for leakage, further dilation, structural changes (with electron microscopy), and changes in wall thickness occurring after 24 hours of perfusion at pressures of 300–350 mmHg. Both 3- and 4-mm thinwalled PTFE could be dilated to five times their initial diameter before rupture occurred. Three-millimeter grafts dilated to 12- and 4-mm grafts dilated to 14 mm remained resistant to leakage at perfusion pressures up to 350 mmHg. When 3-mm grafts were dilated to 15 mm, the PTFE leaked saline at a rate of 20.3 ± 9.3 cc per hour at 300 mmHg. pressure. Four-millimeter grafts dilated to 16- and 20-mm diameters leaked saline at 8.4 ± 7.8 and 52.8 ± 22 cc per minute, respectively, at the same pressure. No grafts were found to increase in diameter after 24 hours of pressure perfusion. Electron microscopy revealed that PTFE node size was significantly smaller in dilated grafts than in undilated grafts, but there was no significant change in internodal distance. This data suggests that thinwalled PTFE can be dilated to large diameters and retain sufficient strength to resist supraphysiologic pressures. Long-term studies are needed to determine the late structural integrity of dilated PTFE.

No abstract.

Focal nodular hyperplasia (FNH) is a benign liver condition, which generally does not contain fat. In this report we describe an unusual case in which multiple areas of FNH were surrounded by prominent peripheral fatty infiltration.