Prospective assessment of resection margin status following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma after standardisation of margin definitions.

BACKGROUND: Surgical resection remains the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). The prognostic value of resection margin status following pancreatoduodenectomy (PD) remains controversial. Standardised pathological assessment increases positive margins but limited data is available on the significance of involved margins. We investigated the impact of resection margin status in PDAC on patient outcome. METHOD: We identified all patients with PD for PDAC at one pancreatic cancer centre between August 2008 and December 2014. Demographic, operative, adjuvant therapeutic and survival data was obtained. Pathology data including resection margin status of specific anatomic margins was collected and analysed. RESULTS: 107 patients were included, all pathologically staged as T3 with 102 N1. 87.9% of patients were R1 of which 53.3% showed direct extension to the resection margin. Median survival for R0 patients versus R1<1 mm and R1 = 0 mm was 28.4 versus 15.4 and 25.1 versus 13.4 months. R1 = 0 mm status remained a predictor of poor outcome on multivariate analysis. Evaluation of individual margins (R1<1 mm) showed the SMV and SMA margins were associated with poorer overall survival. Multiple involved margins impacted negatively on outcome. SMA margin patient outcome with R1 = 1-1.9 mm was similar to R1=>2 mm. CONCLUSION: Using an R1 definition of <1 mm and standardised pathology we demonstrate that R1 rates in PDAC can approach 90%. R1 = 0 mm remained an independent prognostic factor for overall survival. Using R1<1 mm we have shown that involvement of medial margins and multiple margins has significant negative impact on overall survival. We conclude that not all margin positivity has the same prognostic significance.

Simultaneous liver resection and double cardiac valve replacement. A case report.

INTRODUCTION: We present a rare case in which both a double cardiac valve replacement was performed as well as a hepatic resection. PRESENTATION OF CASE: We report the case of a 36 year old patient who presented with intra abdominal bleeding thought to have been caused by a liver haemangioma she also had severe autoimmune cardiac valve disease. She underwent a simultaneous right hepatectomy with cardiac valve replacement. DISCUSSION: Management of this challenging case is discussed. CONCLUSION: We advocate the possibility of performing combined operations where both valve replacement and hepatic resection is required.

Primary hepatic Ewing's sarcoma with cytogenetic confirmation.

INTRODUCTION: Extraskeletal Ewing's sarcoma is reported in the medical literature, but none has been described as presenting with a resectable liver mass. METHODS: A case of a 29-year-old male patient who presented with a large symptomatic mass in the right lobe of the liver which, following resection, demonstrated the characteristic histopathology and fusion protein (EWSR1-Fli1) found in Ewing's sarcoma was reported. DISCUSSION: Complete surgical resection offers the best long-term outlook. Cure rates with appropriate surgical and chemotherapeutic management range between 30 and 60 %.

Comparison of endoscopic ultrasound and computed tomography in the assessment of pancreatic cyst size using pathology as the gold standard.

BACKGROUND/OBJECTIVES: Accurate assessment of whether a cyst is greater than 3 cm is an essential component when considering resection especially for mucinous lesions. The most accurate method of assessing cyst size is uncertain with many patients undergoing several complimentary imaging modalities. This study aimed to compare the accuracy of endoscopic ultrasound (EUS) with CT scanning in assessing pancreatic cyst size compared to histology. METHODS: Patients referred for EUS of a pancreatic cystic lesion from April 2003 to August 2011. Patient age and gender, lesion size and site were recorded and compared using cyst size at histology compared to EUS and CT recorded within 3 months of surgery. Subgroup analysis was performed with respect to cyst site and proven mucinous lesions. RESULTS: 357 patients were included of which 70 (mean age 60.6 years, 24 males) had undergone surgical resection. The resected cysts were located 30/17/23 in the head/body/tail of the pancreas. Median size at histology was 32 mm compared to 35 mm at EUS (p = 0.47) and 35 mm at CT (p = 0.52). For mucinous lesions alone, median size at histology was 32 mm compared to 33 mm at EUS (p = 0.46) and 35 mm at CT (p = 0.39). EUS and CT had comparable sensitivity, specificity, negative predictive value, positive predictive value and accuracy for all cyst types and locations. CONCLUSIONS: CT and EUS measurements are not significantly different to pathological size following resection of pancreatic cystic lesions. CT and EUS are interchangeable investigations for determining cyst size pre-operatively although EUS has the additional advantage of fluid sampling.

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.

Isolated splenic metastasis from renal cell carcinoma: case report and review.

This report presents the case of a 70-year-old woman with a previous history of a left nephrectomy for renal cell carcinoma (RCC), who developed general malaise and fatigue. Abdominal computed tomography demonstrated an enhancing 6 × 7 cm necrotic lesion in the lower pole of the spleen suggestive of a metastasis. Given the highly suspicious nature of the lesion we proceeded to splenectomy. The tumour did not breach the splenic capsule, and there was no local diaphragmatic involvement. The mass was concluded to be a true metastasis of the original RCC rather than local recurrence of the disease. The causes of isolated solid splenic lesions are wide and varied, however a past or present history of malignancy should lead to a high index of suspicion for a splenic metastasis. We report an extremely unusual case of spread from a RCC.

Hepatic Metastasis via a Ventriculo-Peritoneal Shunt from an Intracranial Meningioma: Case Report and Review of the Literature.

Meningiomas are slow-growing intracranial/intraspinal tumours, with a wide range of histopathological variants. The more aggressive atypical and malignant types can disseminate via the venous system, lymphatics or cerebrospinal fluid, with the lungs and pleura being the most common site of extracranial metastasis. We look at a 68-year-old woman presenting with abdominal pain, who had previously been treated for an intracranial meningioma with a ventriculo-peritoneal shunt in situ. Investigation revealed a lesion in segment 4 of the liver with the shunt tip being in close proximity. Biopsy was consistent with metastatic meningioma. A liver resection was subsequently performed. We postulate that this is the first reported case of dissemination of an intracranial meningioma via cerebrospinal fluid by means of a ventriculo-peritoneal shunt.

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. AIM: To evaluate the progression of liver injury in patients with psoriasis and the impact of monitoring by liver biopsy on their management. METHODS: One hundred and twenty-one liver biopsies from 66 subjects (aged 11-79 years) with psoriasis, receiving a median cumulative dose of 3206 mg of methotrexate over a period of 280.5 weeks, were evaluated. RESULTS: The assessment of advanced fibrosis according to the Ishak system (>or= 4) correlated perfectly with that of the Scheuer system (>or= 3) and poorly with that of the Roenigk scale (>or= 3b) (r2 = 1.0 and 0.31, respectively). Two of 24 pre-treatment biopsies showed advanced fibrosis and both subjects were heavy drinkers. The cumulative probabilities of advanced fibrosis (Ishak >or= 4) were 0%, 2.6%, 2.6%, 8.2% and 8.2% at cumulative doses of 1500, 3000, 4500, 5000 and 6000 mg, respectively. None of the subjects developed cirrhosis during follow-up or discontinued therapy on the basis of liver biopsy findings. CONCLUSIONS: Advanced hepatic fibrosis with low-dose methotrexate therapy is much less frequent than previously reported. Pre-treatment or monitoring liver biopsies in accordance with the current guidelines have little impact on patient management.

Type 1 growth factor receptor expression in node positive breast cancer: adverse prognostic significance of c-erbB-4.

BACKGROUND: There is a clear need to define biological markers that will predict the response to treatment in breast cancer, and several recent studies suggest that the expression of type 1 growth factor receptors may prove important in this regard. The type 1 growth factor receptors are a family of transmembrane receptors comprising epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3, and c-erbB-4. Both EGFR and c-erbB-2 are associated with poor prognosis in certain tumours. AIMS: There is very little information concerning expression patterns of the full range of type 1 growth factor receptors, especially with respect to c-erbB-3 and c-erbB-4. Therefore, this study was designed to compare the expression of each, and to assess whether expression of any of the factors was related to patient survival in a clinical series. METHODS: Type 1 growth factor receptor expression was investigated by means of immunohistochemistry in a series of node positive patients with breast cancer (n = 66), and statistical analysis was carried out to determine associations between variables and survival analysis for each variable. RESULTS: There were several correlations between variables, and overexpression of EGFR, c-erbB-2, and c-erbB-4 was found to be associated with adverse clinical outcome, although the results were significant only for c-erbB-4 (p = 0.002). CONCLUSION: Although patient numbers are small, this is the first report describing c-erbB-4 as an adverse prognostic marker. These findings are in contrast to previous investigations and may relate to the fact that the patients studied all had advanced stage disease and had undergone similar chemotherapy regimens in the context of a clinical trial.

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.