Impact of smoking, alcohol consumption, and NSAID use on risk for and phenotypes of eosinophilic esophagitis.

There are few data exploring modifiable risk factors for eosinophilic esophagitis (EoE). We aimed to determine if smoking, alcohol consumption, and nonsteroidal anti-inflammatory drug (NSAID) use were risk factors for EoE, and to assess their impact on EoE phenotypes and treatment outcomes. We performed a case-control study analyzing data collected from a prospective cohort of adults undergoing upper endoscopy for symptoms of esophageal dysfunction. Incident EoE cases were diagnosed via consensus guidelines. Exposure data were collected via standardized patient questionnaire. Follow-up assessments for cases were made after treatment, with histologic response defined as <15 eosinophils per high-power field (eos/hpf). Exposures were compared between EoE cases and controls, among EoE cases with and without fibrostenosis, and among EoE responders and nonresponders. A total of 115 cases and 225 controls were analyzed. Cases were less likely to have ever smoked cigarettes (23% vs. 47%, P < 0.001) or currently use NSAIDs (17% vs. 40%, P < 0.001) compared to controls. These relations persisted after multivariate analysis. Although alcohol use was more common among cases (75% vs. 51%, P < 0.001), the effect was abrogated after multivariate analysis. Smoking, alcohol, and NSAID use were not associated with the fibrostenotic phenotype. There was a trend toward improved histologic response among EoE patients concomitantly using NSAIDs (87% vs. 63%, P = 0.08; aOR 6.97 (95% CI: 0.81-60.3). In conclusion, NSAID and smoking were inversely associated with EoE compared to endoscopy-based controls. Alcohol use was more prevalent in the EoE cases, although not an independent risk factor. Concomitant NSAID use may improve treatment response and is worthy of future study.

Control of inflammation decreases the need for subsequent esophageal dilation in patients with eosinophilic esophagitis.

It is unknown if successful control of esophageal inflammation in eosinophilic esophagitis (EoE) decreases the need for subsequent esophageal dilation. We aimed to determine whether histologic response to topical steroid treatment decreases the likelihood and frequency of subsequent esophageal dilation. We conducted a retrospective cohort study. Patients with an incident diagnosis of EoE were included if they had an initial esophageal dilation, received topical steroids, and had a subsequent endoscopy with biopsies. The number of dilations performed in each group was determined, and histologic responders (<15 eos/hpf) were compared to nonresponders. The 55 EoE patients included (27 responders and 28 nonresponders) underwent a mean of 3.0 dilations over a median follow-up of 19 months. Responders required fewer dilations than nonresponders (1.6 vs. 4.6, P = 0.03), after adjusting for potential confounders. Despite undergoing significantly fewer dilations, responders achieved a similar increase in esophageal diameter with dilation (4.9 vs. 5.0 mm; P = 0.92). In EoE patients undergoing esophageal dilation at baseline, control of inflammation with topical steroids was associated with a 65% decrease in the number of subsequent dilations to maintain the same esophageal caliber. This suggests that inflammation control is an important goal in patients with fibrostenotic changes of EoE.

Prospective assessment of serum periostin as a biomarker for diagnosis and monitoring of eosinophilic oesophagitis.

BACKGROUND: Periostin is highly expressed in eosinophilic oesophagitis (EoE), but has not been extensively studied as a non-invasive biomarker. AIM: To assess whether serum periostin distinguished EoE from controls at baseline, had utility for monitoring treatment response, or was associated with IL-13 levels. METHODS: This was a sub-analysis of a prospective cohort study of adults undergoing out-patient upper endoscopy. Incident cases of EoE were diagnosed per consensus guidelines. Controls were subjects with either GERD or dysphagia without EoE. EoE patients were treated with swallowed/topical steroids and had repeat endoscopy/biopsy. Serum periostin levels for cases and controls were compared at baseline, and pre/post-treatment levels were compared for cases. Serum IL-13 and tissue expression of periostin were also assessed. RESULTS: A total of 61 incident EoE cases and 87 controls were analysed. Despite a marked increase in tissue periostin expression in cases, the median baseline serum periostin level was only slightly higher in cases than controls (22.1 ng/mL vs. 20.7; P = 0.04); there was no change in post-treatment levels. There was also no difference in serum periostin for cases by histologic response or atopic status. There was a strong trend towards higher serum IL-13 levels in cases in the highest periostin quartile (57.1 pg/mL vs. 2.6; P = 0.07). CONCLUSIONS: Serum periostin levels were similar in cases and controls, and there were no changes post-treatment. Given elevated IL-13 levels in the EoE patients with the highest periostin levels, future studies could explore periostin as a biomarker in EoE, perhaps in the setting of anti-IL-13 therapy.

Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity.

BACKGROUND: Knowledge about determinants of quality of life (QoL) in eosinophilic oesophagitis (EoO) patients helps to identify patients at risk of experiencing poor QoL and to tailor therapeutic interventions accordingly. AIM: To evaluate the impact of symptom severity, endoscopic and histological activity on EoE-specific QoL in adult EoE patients. METHODS: Ninety-eight adult EoE patients were prospectively included (64% male, median age 39 years). Patients completed two validated instruments to assess EoE-specific QoL (EoO-QoL-A) and symptom severity (adult EoE activity index patient-reported outcome) and then underwent esophagogastroduodenoscopy with biopsy sampling. Physicians reported standardised information on EoE-associated endoscopic and histological alterations. The Spearman's rank correlation coefficient was calculated to determine the relationship between QoL and symptom severity. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms, endoscopic and histological findings explain variations in QoL. RESULTS: Quality of life strongly correlated with symptom severity (r = 0.610, P < 0.001). While the variation in severity of symptoms, endoscopic and histological findings alone explained 38%, 35% and 22% of the variability in EoE-related QoL, respectively, these together explained 60% of variation. Symptom severity explained 18-35% of the variation in each of the five QoL subscale scores. CONCLUSIONS: Eosinophilic oesophagitis symptom severity and biological disease activity determine QoL in adult patients with eosinophilic oesophagitis. Therefore, reduction in both eosinophilic oesophagitis symptoms as well as biological disease activity is essential for improvement of QoL in adult patients. Clinicaltrials.gov number, NCT00939263.

Markers of tyrosine kinase activity in eosinophilic esophagitis: a pilot study of the FIP1L1-PDGFRα fusion gene, pERK 1/2, and pSTAT5.

The pathogenesis of eosinophilic esophagitis (EoE) is incompletely understood. In certain eosinophilic diseases, activation of tyrosine kinase after fusion of the Fip1-like-1 and platelet-derived growth factor receptor-α genes (F-P fusion gene) mediates eosinophilia via downstream effectors such as extracellular-regulated kinase (ERK1/2) and signal transducers and activators of transcription (STAT5). This mechanism has not been examined in EoE. Our aim was to detect the F-P fusion gene, pERK1/2, and pSTAT5 in esophageal tissue from patients with EoE, gastroesophageal reflux disease (GERD), and normal controls. We performed a cross-sectional pilot study comparing patients with steroid-responsive and steroid-refractory EoE, to GERD patients and normal controls. EoE cases were defined by consensus guidelines. Fluorescence in situ hybridization (FISH) was performed to detect the F-P fusion gene and immunohistochemistry (IHC) was performed to detect pERK1/2 and pSTAT5 in esophageal biopsies. Twenty-nine subjects (median age 30 years [range 1-59]; 16 males; 24 Caucasians) were included: eight normal, six GERD, and 15 EoE (five steroid-refractory). On FISH, 98%, 99%, and 99% of the nuclei in the normal, GERD, and EoE groups, respectively, were normal (P= 0.42). On IHC, a median of 250, 277, and 479 nuclei/mm(2) stained for pERK 1/2 in the normal, GERD, and EoE groups, respectively (P= 0.07); the refractory EoE patients had the highest degree pERK 1/2 staining (846 nuclei/mm(2); P= 0.07). No trend was seen for pSTAT5. In conclusion, the F-P fusion gene was not detected with increased frequency in EoE. Patients with EoE had a trend toward higher levels of pERK 1/2, but not STAT5, in the esophageal epithelium, with highest levels in steroid-refractory EoE patients.

Isolated donor specific alloantibody-mediated rejection after ABO compatible liver transplantation.

Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d.

MRI of carcinoid tumors: spectrum of appearances in the gastrointestinal tract and liver.

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.

Chronic hepatitis: correlation of early patchy and late linear enhancement patterns on gadolinium-enhanced MR images with histopathology initial experience.

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.

Neuroendocrine tumors of the pancreas: spectrum of appearances on MRI.

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 histologically 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.

Perilesional enhancement of hepatic metastases: correlation between MR imaging and histopathologic findings-initial observations.

PURPOSE: To correlate perilesional enhancement on gadolinium-enhanced magnetic resonance (MR) images with histopathologic findings in patients with hepatic metastases. MATERIALS AND METHODS: In seven patients with histopathologically proved hepatic metastases, MR images obtained before and early and late after the administration of gadopentetate dimeglumine were retrospectively evaluated for perilesional enhancement. The thickness of hepatic parenchyma with intense perilesional enhancement was calculated. The thickness of the histologic tumor border (the zone separating the outermost border of the tumor nodule from the surrounding hepatic parenchyma) also was measured. RESULTS: In three patients, early gadolinium-enhanced images showed prominent perilesional enhancement, which correlated with a thick tumor border containing peritumoral desmoplastic reaction, peritumoral inflammation, and vascular proliferation at histopathologic examination. In one patient, mild perilesional enhancement was shown. At histopathologic examination, the lesion periphery showed moderate peritumoral changes. In the remaining three patients, no perilesional enhancement was observed, and at histopathologic examination there was a thin tumor border that contained minimal to mild perilesional changes. The thickness of hepatic parenchyma with intense perilesional enhancement on early gadolinium-enhanced images showed a strong positive correlation with tumor border thickness at histopathologic examination (r = 0.99). CONCLUSION: Intense perilesional enhancement of metastases on early gadolinium-enhanced MR images correlates with histopathologic hepatic parenchymal changes, which include peritumoral desmoplastic reaction, inflammatory cell infiltration, and vascular proliferation.

Islet cell tumor of the pancreas associated with tumor thrombus in the portal vein.

We report the MR findings of a 70-year-old man with an islet cell tumor that diffusely involved the body of the pancreas associated with enhancing portal vein tumor thrombus and cavernous transformation. The diffusely infiltrative tumor mass was best shown on early post gadolinium spoiled gradient echo. The tumor thrombus enhanced intensely on early post gadolinium images and was also well shown on true FISP (Fast Imaging with Steady State Precession) images. The extent of liver metastases was best shown on fat suppressed T2-weighted images. The most unusual finding was tumor thrombus involving the SMV and portal vein.

Biliary hamartomas: solitary and multiple lesions shown on current MR techniques including gadolinium enhancement.

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.

Chemotherapy-treated liver metastases mimicking hemangiomas on MR images.

BACKGROUND: To report the observation that chemotherapy-treated liver metastases may mimic the appearance of hemangiomas on T2-weighted and serial postgadolinium gradient-echo magnetic resonance (MR) images. METHODS: T2-weighted and serial postgadolinium spoiled gradient-echo images were prospectively and retrospectively analyzed in six patients. All patients had been treated with chemotherapy for a duration of 2-12 months. Histopathologic evaluation of liver lesions was performed in three patients. RESULTS: Twelve lesions that resembled hemangiomas were identified. Lesions were 0.8-5.5 cm in diameter. All were well defined, oval or lobulated, and demonstrated decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. On immediate postgadolinium images, all lesions demonstrated peripheral nodular enhancement, which coalesced on delayed imaging. Final histopathologic diagnoses were as follows: hepatic metastases from colon cancer (two patients), ovarian cancer (two patients), pancreatic islet cell tumor (one patient), and breast cancer (one patient). CONCLUSIONS: Metastases treated by chemotherapy may mimic the appearance of hemangiomas on a variety of commonly employed MR techniques. In patients undergoing MR imaging for the evaluation of liver metastases, a history of prior chemotherapy administration and duration should be sought to prevent inaccurate staging and inappropriate therapeutic decision making.

MRI of normal and abnormal duodenum using Half-Fourier Single-Shot RARE and gadolinium-enhanced spoiled gradient echo sequences.

The objective of this research was two-fold: First, to describe the normal and abnormal MR appearances of the duodenum using combined Half-Fourier Acquisition Single Shot RARE (HASTE) and gadolinium-enhanced standard and fat suppressed spoiled gradient echo (SGE) sequences. The second objective was to assess the ability of these combined sequences to detect and characterize duodenal diseases. MR examinations were performed on fifty consecutive patients with no clinical history of duodenal diseases, who were 1) imaged with HASTE and gadolinium-enhanced standard and fat suppressed SGE sequences and 2) referred to MR examination for reasons other than duodenal diseases, and were reviewed retrospectively to determine the normal MR appearances of the duodenum. A second population of patients with abnormal duodenum who were imaged with the same MR sequences were included in the second part of this study. This population was composed of 20 consecutive patients with subsequently proven duodenal abnormalities, including: malrotation (2), diverticula (4), intussusception (1), sprue (1), polyps (2), neurofibroma (1), lymphoma (1), Zollinger Ellison syndrome (1), metastatic disease (1), Crohn's disease (1), and wall thickening and duodenitis (5). Normal measurements of the duodenum are described. Abnormalities of wall thickness and duodenal masses required combined HASTE and gadolinium-enhanced SGE images to evaluate well. Abnormalities of the bowel lumen (e.g., diverticula and intussusception), and developmental variants (e.g., malrotation), were sufficiently visualized on HASTE images alone. Bowel inflammation was best shown on gadolinium-enhanced fat suppressed SGE images. HASTE and gadolinium-enhanced fat suppressed SGE sequences are complementary techniques for the demonstration of normal and abnormal duodenum. The combined use of both sequences allows evaluation of different aspects of bowel diseases; abnormalities of position, lumen, and contents are well shown on HASTE, while inflammation is best shown on gadolinium enhanced fat suppressed SGE, and wall thickening and masses are best evaluated with the combined use of both techniques.

Complex renal cysts: findings on MR imaging.

OBJECTIVE: We retrospectively evaluated our experience with complex cystic renal masses on MR imaging, using T1-weighted, T2-weighted, and gadolinium-enhanced images, to determine whether imaging features could permit distinction between benign and malignant lesions. MATERIALS AND METHODS: Thirty-seven patients with complex cystic renal lesions were included in this retrospective study. The patients selected had undergone T1-weighted, T2-weighted, and gadolinium-enhanced MR imaging examinations using 1.5-T scanners, with at least one of the following findings: cyst fluid of heterogeneous signal intensity, mural irregularity, septa, mural masses or nodules, increased mural thickness, or intense mural enhancement. The diagnosis was established by histology in 19 patients and by follow-up studies in the remaining 18 patients. RESULTS: Fifty-five complex renal cystic lesions were present in the 37 patients. Among the 55 lesions, of 37 that contained fluid of a heterogeneous signal intensity, eight were malignant (22%); of 16 with irregular walls, 10 were malignant (63%); of four with septa, two were malignant (50%); of four with mural masses or nodules, three were malignant (75%); of 14 with a thick wall (>2 mm), 10 were malignant (71%); and of 32 with intense mural enhancement, 14 were malignant (44%). As independent variables, mural irregularity, mural masses or nodules, increased mural thickness, and intense mural enhancement each were highly associated with malignancy (p = .0003-.0022). The combination of mural irregularity and intense mural enhancement had the highest correlation with malignancy (p = .0002). CONCLUSION: The combination of mural irregularity and intense mural enhancement is a strong predictor of malignancy in renal cystic lesions. However, the appearance of benign and malignant lesions may overlap, suggesting that distinct separation of these entities is not currently possible in all cases with MR imaging.

Cholangiocarcinoma: spectrum of appearances on MR images using current techniques.

This study describes the spectrum of appearances of cholangiocarcinoma on magnetic resonance (MR) sequences, including gadolinium-enhanced, fat-suppressed spoiled gradient echo images and MR cholangiography. Fifteen patients were included in the study. Histologic diagnosis was established in 11 patients by surgical resection (6 patients), percutaneous biopsy (4 patients), and open liver biopsy (1 patient). The final diagnosis was determined by correlation of the MR findings with cholangiographic studies and laboratory studies in 4 patients. MR studies were performed at 1.5 T, and the following sequences were obtained: T1-weighted spoiled gradient echo (SGE), T1-weighted fat-suppressed spin echo or SGE, T2-weighted fat-suppressed conventional or turbo spin echo, MR cholangiography, and gadolinium-enhanced T1-weighted fat-suppressed SGE images. The following determinations were made: tumor location, tumor extent, ductal dilatation, ductal wall thickness, signal intensity, enhancement pattern, and associated findings. Mass-like neoplasms were peripheral (6 patients), hilar (1 patient), and extrahepatic (2 patients). Circumferential tumors were hilar (2 patients) and extrahepatic (4 patients). All peripheral tumors were multifocal. Mass-like tumors were well-defined, rounded, and ranged from 1 to 14 cm in diameter. Circumferential tumors had less well-defined margins and measured from 3 to 15 mm in thickness. All mass-like tumors were moderately hypointense on T1-weighted images and mildly to moderately hyperintense on T2-weighted images. The circumferential tumors were iso- to moderately hypointense on T1-weighted images and iso- to mildly hyperintense on T2-weighted images. Mass-like tumors were generally well shown on non-contrast and immediate gadolinium-enhanced images, whereas circumferential tumors were poorly seen on non-contrast images and best shown on gadolinium-enhanced T1-weighted fat-suppressed images. The degree of enhancement ranged from minimal to intense on immediate gadolinium-enhanced images, with all tumors becoming more homogeneous in signal intensity on images obtained between 1 and 5 min following contrast administration. Tumor-containing lymph nodes greater than or equal to 1 cm in diameter were demonstrated in 11 out of 15 patients (73.3%). These were best shown on T2-weighted fat-suppressed images and gadolinium-enhanced fat-suppressed SGE images. MR cholangiography demonstrated the level of obstruction and degree of dilatation of the proximal biliary system in 5 out of 6 patients who underwent MR cholangiography. The spectrum of appearances of cholangiocarcinoma is demonstrable on MR images. Mass-like tumors are well shown on both pre- and post-gadolinium sequences. Circumferential tumors may cause minimally increased duct wall thickness and are most clearly shown on gadolinium-enhanced fat-suppressed SGE images obtained 1 to 5 min following gadolinium administration.

Rectal mucosal proliferation, dietary factors, and the risk of colorectal adenomas.

Colorectal cancer arises from a series of precursor stages, the so called adenoma-carcinoma sequence. Increased rectal mucosal proliferation may be an early step in this sequence. Because dietary factors are implicated in the etiology of colorectal cancer, one might predict that diet would also be associated with proliferation. We conducted this study to examine the association of diet with rectal mucosal proliferation. Rectal mucosal proliferation was measured in endoscopic biopsy specimens by proliferating cell nuclear antigen (PCNA) immunohistochemistry and whole crypt mitotic counts (WCMCs). Diet was evaluated using a validated quantitative food frequency questionnaire. The correlation between PCNA labeling index (LI) and WCMCs was determined using Kendall's tau, a nonparametric measure of correlation. Logistic regression was used to examine the effect of proliferation on adenoma status, controlling for confounders. The relationship between proliferation and dietary and demographic factors was examined using linear regression. There were 308 patients who had one or both measures of proliferation. There was no significant correlation between PCNA LI and WCMCs (Kendall's tau = 0.04; P = 0.35). Neither measure of proliferation was predictive of adenoma status, even after adjusting for potential confounders. Body mass index and calories per day were significant predictors of WCMC (P = 0.01 and P = 0.03, respectively). PCNA labeling index was not associated with any dietary variables, although its association with dietary fat nearly reached statistical significance (P = 0.09). The association between proliferation and diet were generally inconsistent. There appears to be no simple relationship between colorectal cancer risk factors, colorectal adenomas, and these two measures of rectal mucosal proliferation. We need simpler, more reliable intermediate markers for use in etiological and intervention studies.