Comparison of LI-RADS with other non-invasive liver MRI criteria and radiological opinion for diagnosing hepatocellular carcinoma in cirrhotic livers using gadoxetic acid with histopathological explant correlation.

AIM: To establish the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) and compare its performance to that of international criteria from European Assofor the Study of the Liver (EASL), Japan Society of Hepatology (JSH), Asian Pacific Association for the Study of the Liver (APASL), and Organ Procurement and Transplantation Network (OPTN), and to the reporting radiologist's overall opinion regarding the probability of a nodule being a HCC by correlating with a histological diagnosis from whole liver explants. MATERIALS AND METHODS: The present single-centre, retrospective review selected participants based on the following criteria: adults (≥18 years) listed for liver transplantation in 2014/2015, with liver cirrhosis at the time of magnetic resonance imaging (MRI) with hepatocyte specific contrast agent, and at least one liver lesion ≥10 mm on MRI with histology from subsequent liver explant for comparison. Each lesion was assessed against international criteria and given a "radiologist opinion" score of 1-5 (1 = definitely benign, 5 = definitely HCC). RESULTS: Total 268 patient records were reviewed, with 105 eligible lesions identified from 47 patients. Median lesion size was 15.5 mm (range 10-68 mm). Sensitivity (%), specificity (%), and positive predictive value (PPV; %) for LI-RADS LR5 was 45, 89, and 89, for LI-RADS LR4+5 + TIV was 61, 80, and 86, for EASL was 44, 86 and 86, for JSH/APASL was 64, 81, and 87, for OPTN was 36, 90, and 88, and for "radiologist impression" of probably or definitely HCC was 79, 79, and 88 respectively. CONCLUSIONS: MRI has moderate sensitivity and good specificity for the diagnosis of HCC with considerable variation depending on criteria used. OPTN criteria have the best specificity, but low sensitivity. "Radiologist opinion" gives highest overall accuracy with increases in sensitivity and reduction in specificity when compared to the imaging criteria.

Liver histopathology in the Yorkshire region: a network model.

AIM: To investigate the volume and provision of local liver histopathology in the 11 hospitals of the Yorkshire region outside Leeds, as a potential model for a hepatopathology network. METHODS: Postal questionnaire to all histopathologists in 11 hospital trusts in Yorkshire. RESULTS: Liver biopsies represent about 0.5% histopathology requests in Yorkshire, with more medical than tumour biopsies. Pathologists often discuss these biopsies with each other and clinicians; a third had done liver continuing professional development (CPD) in the last 3 years, and 70% would like to do more. Overall, around 5% liver biopsies are reviewed in the hepatology centre, and most responders thought this about right. CONCLUSIONS: For primary reporting of liver biopsies, local pathologists need good communication with the responsible clinician, access to relevant CPD in liver pathology and a biopsy referral pathway for cases which are clinically or pathologically challenging.

Surgeon's awareness of the synchronous liver metastases during colorectal cancer resection may affect outcome.

AIM: There is conflicting evidence about the importance of synchronous metastases upon tumor outcome. The aim of this study is to identify the effect of finding synchronous colorectal liver metastases on the performance of the surgeon whilst operating on primary colorectal cancer. METHODS: Patients with completed colorectal cancer data who underwent liver resection for colorectal metastases between 1993 and 2001 were included. Two hundred seventy patients were categorised according to the site of the primary tumour (colon or rectum) and knowledge of the presence of liver metastases by the colorectal surgeon (SA=surgeon aware, n=112, SNA=surgeon not aware, n=158). The number of retrieved lymph nodes and colorectal resection margin involvement were used as surgical performance indicators. Survival and local recurrence rate were monitored. RESULTS: The SA group had a higher rate of colorectal circumferential resection margin involvement, the local and intra-abdominal recurrence rate was also significantly higher in this group (p<0.001). CONCLUSIONS: Awareness of the presence of liver metastases by the operating surgeon is an independent predictor of intra abdominal extra hepatic recurrence of colorectal cancer following potentially curative hepatic resection. This is related to an increased rate of primary colorectal resection margin involvement.

Granulomatous infiltration with replacement of liver parenchyma: first case report.

A 76-year-old man presented with fever, weight loss and abnormal liver function tests. Imaging demonstrated a diffusely abnormal liver, and a liver biopsy revealed a fibrosing granulomatous process infiltrating and replacing liver parenchyma. There was no clinical, radiological or laboratory evidence of autoimmune liver disease, sarcoidosis, lymphoma or tuberculosis. Treatment with steroids resulted in a remarkable resolution of the clinical symptoms and radiology. This is the first case of granulomatous infiltration of the liver replacing normal hepatic parenchyma.

A case of Sister Mary Joseph nodule associated with primary gastric lymphoma.

The Sister Mary Joseph nodule is a peri-umbilical metastasis most commonly found with adenocarcinomas of the gastrointestinal tract and ovary. It was first described 140 years ago but has not previously been reported in association with primary gastric lymphoma.

Liver transplantation for a hilar inflammatory myofibroblastic tumor.

A 7-yr-old boy presented with obstructive jaundice secondary to an inflammatory myofibroblastic tumor centered on the hepatic hilum and extending into the liver. The tumor was further complicated by portal vein phlebitis and occlusion. Attempted resection of the tumor with portal vein reconstruction and bilioenteric drainage was unsuccessful and he required urgent orthotopic liver transplantation. In contrast to more peripheral inflammatory myofibroblastic tumors in the liver, hilar lesions are locally aggressive, causing occlusive portal phlebitis and biliary obstruction. Successful management may include the need for liver transplantation.

Systemic cytomegalovirus infection complicating ulcerative colitis: a case report and review of the literature.

Cytomegalovirus is a common infection worldwide and in the immunocompromised individual it can be a major cause of morbidity and mortality. In patients with inflammatory bowel disease cytomegalovirus infection has been described in both immunocompetent and immunocompromised individuals. A 34 year old man with an exacerbation of his colitis was diagnosed as having both cytomegalovirus colitis and hepatitis. The diagnosis was made on the classical appearance of "owl's eye" inclusion bodies on colonic and hepatic biopsies and, in addition, viral serology and polymerase chain reaction (PCR) analysis of the cytomegalovirus DNA copy number. Fourteen days of treatment with ganciclovir led to a prompt improvement in the symptoms of colitis, resolution of the pyrexia, normalisation of the liver function tests, and clearance of the virus, as measured by a negative cytomegalovirus DNA PCR. Cytomegalovirus infection is a potentially fatal complication of treatment induced immunosuppression in patients with inflammatory bowel disease. As in this case, infection may be systemic and not confined to the intestine. Prompt diagnosis using histology, serology, and PCR analysis allows prompt introduction of therapy and an improved prognosis.

The pathology of acute hepatic disintegration in hereditary haemorrhagic telangiectasia.

AIMS: Hereditary haemorrhagic telangiectasia is a rare inherited disease in which telangiectases affect skin, mucous membranes and the gastrointestinal tract. Hepatic involvement is common but usually asymptomatic. We report a case of acute hepatic disintegration in hereditary haemorrhagic telangiectasia, document the histopathological findings and present a hypothesis to explain them. METHODS AND RESULTS: The patient presented at the age of 34 years with abdominal pain, leading to the surgical removal of a severely inflamed gallbladder. Signs of liver damage became increasingly apparent over the next few weeks, with disruption of the intrahepatic biliary tree and marked vascular shunting, necessitating liver transplantation. Six months after the transplant a diagnosis of hepatic hereditary haemorrhagic telangiectasia was made. The principal features of hepatic hereditary haemorrhagic telangiectasia are periportal telangiectases and sinusoidal congestion and dilatation. Acute hepatic disintegration is characterized by disruption of liver structure, hepatocyte necrosis, haemorrhage and extravasation of bile. CONCLUSIONS: Periportal telangiectases in a liver biopsy are highly suggestive of hereditary haemorrhagic telangiectasia. Acute hepatic disintegration is likely to be a consequence of rupture of telangiectases and ischaemic necrosis of intrahepatic bile ducts. Patients with hereditary haemorrhagic telangiectasia are at risk of acute hepatic disintegration following intra-abdominal sepsis.

Treatment of metastatic breast cancer with liver transplantation.

Resection of liver metastases is accepted as an appropriate treatment for colorectal metastases in suitable patients. Liver transplant is not often used for malignant disease as there is a high incidence of undetectable micrometastases elsewhere and recurrence is likely. The effects of immunosuppression may also enhance the growth of malignant cells at other sites. We report a case where a young patient with undiagnosed breast cancer with axillary and liver metastases underwent liver transplantation and is effectively leading a normal life 33 months after transplant.

Is a raised intraepithelial lymphocyte count with normal duodenal villous architecture clinically relevant?

BACKGROUND: A raised intraepithelial lymphocyte (IEL) count with normal villous architecture is a recognised finding in latent coeliac disease. Little information is available in cases without gluten sensitive enteropathy in adults. AIMS: To assess the frequency of such a finding in routine practice and to determine whether it is clinically relevant. METHODS: Patients with subjectively increased IELs as the only abnormality were identified prospectively from a routine duodenal biopsy series over a 12 month period. The biopsy specimens in these index cases were re-examined together with two controls with normal histology for each case, and three counts of IEL/100 epithelial cells were made in all samples. The index cases were then contacted and interviewed to obtain clinical information, approximately 12 months from the initial biopsy. Further data were obtained from their clinical records. RESULTS: Fourteen of 626 (2.2%) patients who had duodenal biopsies over the 12 month period had a subjective increase in IELs with normal villous architecture. Fifteen patients with newly diagnosed gluten sensitive enteropathy were also identified during the study period. Formal counting of the index cases and controls revealed a significant difference in IELs/100 epithelial cell counts between the two (mean, 38 (SD, 6.2) v 12.4 (4.6); p < 0.0001). Three of the 14 index cases tested had a positive coeliac antibody test compared with 12 of 15 newly diagnosed patients with coeliac disease and 10 of 93 patients with normal histology. The major clinical diagnostic categories in raised IEL cases were those with positive coeliac serology (n = 3), unexplained anaemia (n = 3), and chronic liver disease (n = 3). Six of 10 patients who were interviewed had ongoing gastrointestinal symptoms one year later. Three patients had had follow up duodenal biopsies, at the discretion of their responsible clinicians, with no change in IEL counts despite the commencement of a gluten free diet in two patients. CONCLUSION: A raised IEL count with normal villous architecture is not uncommon. Six of the 14 patients may have had latent coeliac disease. The cause in at least half of cases is not obvious at present. The finding of a raised IEL count with normal villous architecture is of sufficient clinical importance to be highlighted in routine duodenal biopsy reports.

Variation in serum pepsinogens with severity and topography of Helicobacter pylori-associated chronic gastritis in dyspeptic patients referred for endoscopy.

BACKGROUND: It has long been recognised that specific patterns of gastritis are linked with different gastroduodenal diseases and that serum pepsinogens vary with the histological state of the gastric mucosa. With the discovery of the role of Helicobacter pylori in chronic gastritis and the availability of noninvasive tests for H. pylori infection, individuals with H. pylori gastritis can now be identified without endoscopic biopsy. However, without a knowledge of the pattern and severity of gastritis it is impossible to predict the likelihood of significant associated gastroduodenal pathology. AIMS: The aim of this study was to evaluate the diagnostic potential of serum pepsinogens I and II in predicting the topography and severity of gastritis in H. pylori-infected dyspeptic patients attending for endoscopy. METHODS: Fasting serum was obtained from consecutive dyspeptic patients attending for endoscopy, and pairs of gastric biopsies obtained from the mid-body and antrum. Gastritis was graded according to the Sydney System, and serum pepsinogen levels determined by radio-immunoassay. RESULTS: Sixty-nine dyspeptic patients were studied (mean age: 49.6 years) of whom 34 had H. pylori-associated chronic gastritis (Hp-gastritis) - antral predominant gastritis (APG) in 41.2%, pangastritis (PAN) in 52.9%, and corpus predominant (CPG) in 5.9%. Serum pepsinogen II levels were significantly higher, and the serum pepsinogen I : II ratio significantly lower, in the H. pylori positive group than in other groups. Within the Hp-gastritis group, there was a step-wise decrease in serum pepsinogen I levels with progression from APG through PAN to CPG pattern (a cut-off value of > or = 100 ng/ml would have identified APG with a positive predictive value of 77%, though with low sensitivity). Within the Hp-gastritis group, serum pepsinogen I and II levels were correlated with antral chronic inflammation score and serum pepsinogen II levels also with antral activity score. Serum pepsinogen I and the pepsinogen I : II ratio were lowest in severe gastric corpus atrophy. CONCLUSION: In dyspeptic patients known to be infected with H. pylori, serum pepsinogen values provide an assessment of the overall topography of gastritis, the severity of antral inflammation and the presence of severe corpus atrophy.

Interleukin 10 in Helicobacter pylori associated gastritis: immunohistochemical localisation and in vitro effects on cytokine secretion.

BACKGROUND/AIMS: Interleukin 10 (IL-10) is a counter-inflammatory peptide implicated in the downregulation of human intestinal immune responses. Enhanced secretion of IL-10 has been documented in gastric biopsy organ culture in Helicobacter pylori infection. This study aimed to define the cellular origins of IL-10 in H pylori associated gastritis, and to determine the effects of endogenous IL-10 on proinflammatory cytokine secretion in vitro. METHODS: Endoscopic biopsies were obtained from the gastric antrum at endoscopy from patients with dyspepsia. Two pairs of antral biopsies were cultured in vitro for 24 hours, one pair in the presence of neutralising anti-IL-10 monoclonal antibody, the other pair as controls. The cytokine content of culture supernatants (tumour necrosis factor alpha (TNF-alpha), IL-6, and IL-8) was determined by enzyme linked immunosorbent assay and corrected for biopsy weight. Helicobacter pylori status was established by histology and biopsy urease test, and histopathology graded by the Sydney system. In a subgroup of patients, western blotting was used to establish CagA serological status. Immunohistochemistry for IL-10 was performed on formalin fixed tissues using a combination of microwave antigen retrieval and the indirect avidin-biotin technique. Immunoreactivity was scored semiquantitatively. RESULTS: In vitro culture was performed in 41 patients: 31 with H pylori positive chronic gastritis and 10 H pylori negative. In vitro secretion of TNF-alpha, IL-6, and IL-8 for "control" biopsies was significantly higher in H pylori positive versus negative samples, with values of TNF-alpha and IL-6 correlating with the degree of active and chronic inflammation and being higher in CagA seropositive cases. No evidence for enhanced cytokine secretion was seen in biopsies cocultured in the presence of anti-IL-10 monoclonal antibody. Immunohistochemistry was performed in 29 patients, of whom 13 were H pylori positive. IL-10 immunoreactivity was observed in the surface epithelium in all H pylori positive cases and in 13 of 16 negative cases, especially in areas of surface epithelial degeneration. Lamina propria mononuclear cells (LPMNCs) were positively stained in all H pylori positive cases and in 12 of 16 negative cases, with a significantly greater proportion of positive LPMNCs in the positive group. CONCLUSIONS: This study localised IL-10 protein to the gastric epithelium and LPMNCs. In vitro proinflammatory cytokine secretion was increased in H pylori infection (especially CagA positive infection), but blocking endogenous IL-10 secretion did not significantly increase cytokine secretion. IL-10 is implicated in H pylori infection and might "damp down" local inflammation. The role of gastric IL-10 secretion in determining the clinicopathological outcome of infection merits further study.

Hepatocellular carcinoma in the cirrhotic liver: double-contrast MR imaging for diagnosis.

PURPOSE: To measure the sensitivity and accuracy of double-contrast magnetic resonance (MR) imaging for the diagnosis of hepatocellular carcinoma (HCC) in the cirrhotic liver. MATERIALS AND METHODS: Twenty-seven patients with MR features of dysplastic nodules and/or HCC were examined. T2-weighted spin-echo and T1-weighted gradient-echo imaging was performed before and after superparamagnetic iron oxide (SPIO) administration and immediately followed by T1-weighted gradient-echo imaging at 10, 40, and 120 seconds after bolus injection of a gadolinium-based contrast material. Nonenhanced, nonenhanced plus SPIO-enhanced, and nonenhanced plus SPIO-enhanced plus gadolinium-enhanced images were reviewed. Alternative-free response receiver operating characteristic (ROC) methodology was used to analyze the results, which were correlated with histopathologic findings after transplantation in 15 patients and at biopsy in 12. Lesions visualized with all three techniques were characterized as a dysplastic nodule or HCC, and ROC analysis was performed. RESULTS: For all observers, SPIO-enhanced MR imaging (mean accuracy, 0.76) was more accurate than nonenhanced MR imaging (mean accuracy, 0.64) (P <.04), and double-contrast MR imaging (mean accuracy, 0.86) was more accurate than SPIO-enhanced imaging (P <.05). Both types of lesions were correctly characterized with all three techniques, although observer confidence for lesion characterization was greatest with double-contrast MR imaging. CONCLUSION: Double-contrast MR imaging significantly improves the diagnosis of HCC compared with SPIO-enhanced and nonenhanced imaging (P <.01).

A new cause of 'non-responsiveness' in coeliac disease?

A 42 year old man presented with gluten-responsive coeliac disease and secondary pancreatic insufficiency. Subsequently his symptoms relapsed and repeat small intestinal biopsy showed villous atrophy and infiltration by leukaemic cells, despite continuation of a gluten-free diet. Serious causes of relapse and non-responsiveness in coeliac disease include enteropathy-associated T-cell lymphoma, ulcerative jejunitis and an end-stage hypoplastic mucosa. This is the first report of non-responsiveness due to infiltration by leukaemia.

Triple therapy for Helicobacter pylori eradication: a comparison of pantoprazole once versus twice daily.

BACKGROUND: Proton pump inhibitor-based triple therapy is recommended as treatment for Helicobacter pylori eradication. The proton pump inhibitor may be given once or twice daily. However, little information is available on how these two treatment strategies compare. METHODS: H. pylori-positive patients (two positive test results) with endoscopy-proven healed duodenal ulcer or non-ulcer dyspesia were randomly allocated to 1 week of double-blind treatment with pantoprazole 40 mg once or twice daily, plus clarithromycin 250 mg and metronidazole 400 mg twice daily. Eradication was defined as a negative 13C-urea breath test (13C-UBT) and histology, 4-5 weeks post-treatment. The follow-up phase comprised 12 months off therapy, with 13C-UBT at 6 and 12 months. RESULTS: Two hundred and four patients received treatment: pantoprazole once daily (x1), n=104; twice daily (x2), n=100. Eradication rates were 84% in both the pantoprazole x1 and pantoprazole x2 groups by modified intention-to-treat analysis and 89% and 87%, respectively, by per protocol analysis. Metronidazole resistance was found in 44% of pre-treatment cultures of H. pylori. Eradication rates were similar in susceptible (72%) and resistant (75%) strains. During follow-up, recrudescence of infection occurred in 3/118 patients. CONCLUSION: When using pantoprazole plus clarithromycin and metronidazole, the proton pump inhibitor can be used once daily without loss of efficacy.

Hepatic lesion detection after superparamagnetic iron oxide enhancement: comparison of five T2-weighted sequences at 1.0 T by using alternative-free response receiver operating characteristic analysis.

PURPOSE: To compare the accuracy of five T2-weighted sequences in the detection of liver lesion at magnetic resonance (MR) imaging after superparamagnetic iron oxide (SPIO) enhancement. MATERIALS AND METHODS: Forty-nine candidates for hepatic resection with known coloretal metastases were examined. Before SPIO enhancement, fast spin-echo (SE) images were obtained. After enhancement, the same fast SE sequence and long; TR/short TE, short TE, long TR/TE, and T2-weighted fast low-angle shot (FLASH) sequences were used. All images were viewed independently by four observers who were blinded to the results of the other imaging sequences, the results of the other observers, and the findings at surgery and histopathologic examination. Four weeks after the initial reading, the combined long TR/short TE and long TR/TE dual-echo images were also viewed as an additional set. The alternative free response receiver operating characteristic (ROC) method was used to analyze the results, which were correlated with findings at surgery, intraoperative ultrasonography, and histopathologic examination. RESULTS: Irrespective of lesion size, the accuracy of all sequences after enhancement was significantly greater than that of the nonenhanced fast SE sequence (P < .01). Dual-echo and FLASH sequences were significantly more accurate than the enhanced fast SE sequence (P < .03 or P < .02, respectively). For all lesions, lesions smaller than 1 cm, and lesions 1 cm or larger, mean accuracies were as follows: dual-echo, 0.75, 0.54, and 0.93; FLASH, 0.75, 0.54, and 0.95; and enhanced fast SE, 0.72, 0.49, and 0.92. CONCLUSION: At 1.0 T, dual-echo and FLASH sequences are the most accurate pulse sequences after SPIO enhancement.

Serologic screening before endoscopy: the value of Helicobacter pylori serology, serum recognition of the CagA and VacA proteins, and serum pepsinogen I.

BACKGROUND: We wanted to assess the diagnostic value of pre-endoscopy screening by Helicobacter pylori serology, serum recognition of the CagA and VacA proteins, and serum pepsinogen I levels (sPGI) in patients up to 55 years of age with uncomplicated simple dyspepsia. METHODS: Consecutive dyspeptic patients referred for open-access endoscopy, excluding patients with alarm symptoms, recent intake of acid suppressants, or ingestion of non-steroidal anti-inflammatory drugs. H. pylori status was determined by histology and urease testing. H. pylori serologic status was determined with the enzyme-linked immunosorbent assay (ELISA) and Western blotting, serum recognition of CagA and VacA with Western blot, and sPGI levels by radioimmunoassay. RESULTS: One hundred and fifteen patients were studied (mean age, 40 years: range, 20-55 years), of whom 58 were H. pylori-positive in biopsy-based tests. Twenty-one patients (18%) had significant gastroduodenal lesions (erosions, ulcers, or cancer). The sensitivity (specificity) of the ELISA (optimized) and Western blot in determining H. pylori status was 94.8% (89.5%) and 100% (96.4%), respectively. Screening strategies based on the ELISA or Western blot for determining H. pylori serologic status would have detected 95% or 100% of significant lesions, respectively, and each 'saved' 47% of endoscopies for simple dyspepsia. Serum recognition of the CagA protein would have detected 95% of significant lesions and 'saved' 55% of endoscopies, whereas recognition of the VacA protein would have detected only 81% of the lesions. Screening by H. pylori serology plus a 'low' (<55 ng/ml) or 'high' sPGI (>125 ng/ml) would detect only 57% of significant lesions, although the only case of cancer was included in the hypopepsinogenaemic subgroup of just 11 patients. CONCLUSIONS: In patients with uncomplicated, simple dyspepsia up to 55 years of age, screening by H. pylori serology identified 95%-100% of patients with significant gastroduodenal lesions while potentially saving 46.9% of endoscopies. Serum recognition of the CagA protein identified 95% of lesions and would have saved an additional number of endoscopies (7.9%) compared with basic serology. Measurement of sPGI was of limited diagnostic value.