Beate Haugk

Monitoring methotrexate-induced hepatic fibrosis in patients with psoriasis: are serial liver biopsies justified?

Background : Reports that up to 26% of subjects with psoriasis develop cirrhosis have led to a recommendation of serial liver biopsies after each cumulative dose of 1500 mg of methotrexate.

Metastatic lymph node ratio as an important prognostic factor in pancreatic ductal adenocarcinoma.

BACKGROUND Overall five year survival following pancreaticoduodenectomy for ductal adenocarcinoma is poor with typical reported rates in the literature of 8-27%. The aim of this study was to identify the histological variables best able to predict long-term survival in these patients. METHODS A prospective database of patients undergoing pancreaticoduodenectomy between April 2002 and June 2009 was analysed to identify patients with histologically proven pancreatic ductal adenocarcinoma. Patients with ampullary tumours, cholangiocarcinoma, duodenal adenocarcinoma and neuroendocrine tumours were excluded. The histology reports for these patients were reviewed. Uni-variate and multi-variate survival analysis was performed to identify variables useful in predicting long-term outcome. RESULTS 134 patients underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma during this period. 5 year survival in this series was 18.6%. Uni-variate analysis identified nodal status and the metastatic to resected lymph node ratio as predictors of survival. Using multi-variate Cox Regression analysis a metastatic to lymph node ratio of >15% (p < 0.01) and the presence of perineural invasion (p < 0.05) were identified as independent predictors of patient survival. Metastatic to resected lymph node ratio is better able to stratify prognosis than nodal status alone with 5 year survival of those with N0 disease being 55.6% and 12.9% for N1 disease. However for those with <15% of resected nodes positive, 5 year survival was 21.7% and in those with >15% nodes positive it was 5.2% (p = 0.0017). CONCLUSION The metastatic to resected lymph node ratio can provide significant prognostic information in those patients with node positive disease after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

Pancreatic intraepithelial neoplasia – can we detect early pancreatic cancer?

Haugk B
(2010) Histopathology 57, 503–514
Pancreatic intraepithelial neoplasia – can we detect early pancreatic cancer?

Single centre experience of haematopoietic SCT for patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

Single centre experience of haematopoietic SCT for patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

Reactive lymphoid hyperplasia of the liver and pancreas. A report of two cases and a comprehensive review of the literature.

BACKGROUND Reactive lymphoid hyperplasia (RLH) is a rare non-neoplastic extranodal pathology with exceedingly rare occurrence in the liver and pancreas. We present two cases of hepatic RLH, one which had coinciding pancreatic involvement. To the best of our knowledge, concomitant hepatic and pancreatic RLH has not been previously reported. We also present a comprehensive review of the literature on hepatic and pancreatic RLH. METHODS An extensive literature search for all published reports on hepatic or pancreatic RLH was conducted. Data on clinical, radiographic and histopathological features were extracted in addition to therapeutic options and outcomes. RESULTS Forty-two hepatic and three pancreatic cases of RLH were described in the literature. The mean age of hepatic cases was 58 years, with a male-to-female ratio of above 1:7. Almost 25% of cases were associated with internal malignancy. Four hepatic cases were managed through active observation. The remainder (84%) underwent surgical resection. Due to their small number, no meaningful analysis could be made on the pancreatic cases. No recurrences were identified in any of the reported cases. CONCLUSION RLH should be considered in the diagnosis of hepatic nodules where biopsies fail to demonstrate malignant cells. Confirmed RLH lesions should be managed by active observation. Investigation and treatment of any potential source of lymphoid reactivity should be undertaken. More reports on pancreatic RLH need to be studied prior to drawing any useful recommendations on its management.

Diagnostic Performance of Endoscopic Ultrasound (EUS)/ Endoscopic Ultrasound - Fine Needle Aspiration (EUS-FNA) Cytology in Solid and Cystic Pancreatic Neuroendocrine Tumours

BACKGROUND AND AIMS Our study aimed to assess the sensitivity of EUS and EUS-FNA for pancreatic neuro-endocrine tumors (pNETs) and compare performance over two consecutive 4 year 2 month periods, to investigate the comparative performance between solid and cystic pNETs and determine the incremental yield of EUS +/- FNA in individuals with a mass not diagnosed as a pNET after cross-sectional imaging. METHODS A retrospective review of a prospectively maintained database was carried out to identify all pNET patients who underwent EUS-FNA between April 2003 and September 2011. RESULTS A final diagnosis of solid and cystic pNETs was made in 43 and 10 patients, respectively. Overall, the yield of combined EUS imaging and cytology was significantly higher than that of CT and/or MRI (p< 0.05) across all groups [solid (83.7% vs. 41.8%), cystic (70% vs. 10%) and combined solid-cystic (81.1% vs. 35.8%)]. The yield of combined EUS imaging and cytology was significantly better than EUS imaging alone (p<0.05) in the solid (83.7% vs. 58%) and combined pNET cohort (81.1% vs. 52.8%) of patients. After a non-diagnostic CT and or MRI, EUS/EUS-FNA confirmed pNET in 19 out of 25 patients (76.0%) with solid pNETs and 6 out of 9 patients (66.7%) with cystic pNETs. CONCLUSION EUS and EUS-FNA had a significant clinical impact in the 25/34 of cases where pNET was not suspected after initial cross-sectional imaging.

Expression of topoisomerase IIIalpha in normal and neoplastic tissues determined by immunohistochemistry using a novel monoclonal antibody.

Topoisomerases are nuclear enzymes that modulate the topological structure of DNA in order to facilitate cellular events such as replication and transcription. These enzymes are also the cellular targets of certain classes of chemotherapeutic agents termed topoisomerase poisons. A new human topoisomerase isoform, IIIa, was discovered in 1996, which is thought to have roles in genome stability and possibly chromosome separation during mitosis. It is possible that novel or existing anti-topoisomerase agents target topoisomerase IIIa, suggesting that this enzyme may have potential as a prognostic marker and chemotherapeutic target. In order to study expression patterns of topoisomerase IIIa we have produced a novel monoclonal antibody to human topoisomerase IIIa (TOPO3a-1A4), and used it to assess topoisomerase IIIa expression in a wide range of normal and neoplastic tissues. We have found that topoisomerase IIIa is expressed in a wide range of tissue types, with especially high concentrations in endothelial cells and stromal fibroblasts. No general relationship was observed between expression of topoisomerase IIIa and proliferation. Expression in neoplastic tissues often paralleled their normal counterparts, although certain tumours showed either increased (e.g. colonic adenoma) or reduced (e.g. gastric carcinoma, small cell carcinoma of bronchus) expression. If topoisomerase IIIa is found to be a target for chemotherapeutic agents, clinical response in different tumour types may be related to topoisomerase IIIa expression, which may be assessed using TOPO3a-1A4.

Cytogenetically confirmed primary Ewing’s sarcoma of the pancreas

Ewing’s sarcoma is a highly aggressive malignant tumour most commonly affecting long bones in children and adolescents. It is part of the Ewing’s sarcoma family of tumours (ESFTs) that also include peripheral primitive neuroectodermal tumour and Askin’s tumours. ESFTs share common cytogenetic aberrations, antigenic profiles and proto-oncogene expression with an overall similar clinical course. In 99% of ESFTs, genetic translocation with molecular fusion involves the EWSR1 gene on 22q12. Approximately 30% of ESFTs are extraosseous, most commonly occurring in the soft tissues of extremities, pelvis, retroperitoneum and chest wall. Primary presentation in solid organs is very rare but has been described in multiple sites including the pancreas. Accurate diagnosis of a Ewing’s sarcoma in a solid organ is critical in facilitating correct treatment. We report the case of a 17-year-old girl with cytogenetically confirmed primary pancreatic Ewing’s sarcoma and provide a brief review of the published literature.

Obstetric Liver Disease

Up to 3 % of all gestations are complicated by various liver diseases. Some of these are unique to pregnancy, whereas others are either coincidental with pregnancy or associated with preexisting chronic liver diseases. Severe liver diseases in pregnancy are rare but may lead to significant morbidities and even mortality for both mother and fetus/infant. The major pregnancy-related liver diseases comprise intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, toxaemia of pregnancy, HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet count), hepatic infarction and rupture, and hyperemesis gravidarum.

Fatty Liver Disease

Steatosis is very common and is associated with numerous conditions, the most common of which are alcoholism and the metabolic syndrome. Others include drugs, viruses, disorders of nutrition, and endocrine, metabolic, and systemic diseases. Steatosis manifests histologically as the accumulation of droplets of triglycerides inside the cytoplasm of hepatocytes. The size of these droplets varies from a single large one (macrovesicular steatosis) occupying the cytoplasm almost completely and pushing the nucleus to the periphery, to one or more of medium size (mediovesicular steatosis). The term microvesicular should be used when steatosis manifests as an accumulation of very fine vesicular material, without nuclear displacement, which cannot be differentiated from other accumulations (e.g., glycogen) or cytoplasmic changes (e.g., hydropic degeneration) without the use of special techniques. Microvesicular steatosis usually is associated with a congenital or acquired defect in β-oxidation and severe hepatic dysfunction.