Jennifer Watkins

Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non-alcoholic fatty liver disease patients

Introduction: Differentiation between steatosis and non‐alcoholic steatohepatitis (NASH) in non‐alcoholic fatty liver disease (NAFLD) is important as NASH progress to cirrhosis. No specific laboratory/imaging technique exists either to diagnose NASH or to select patients for liver biopsy.

Redefining the R1 resection for pancreatic ductal adenocarcinoma: tumour lymph nodal burden and lymph node ratio are the only prognostic factors associated with survival

INTRODUCTION The presence of positive nodal disease (LND) and the number of lymph nodes involved (LNB) are known to be significant prognostic markers for resected adenocarcinoma of the pancreas. In addition, the ratio of the number of involved nodes to the number of nodes resected known as the lymph node ratio (LNR) is emerging as an important prognostic marker. The role of the resection margin (RM) as presently defined (R1 ≤ 1 mm) is unclear as results differ based on the dataset. The aim of this study was to assess the impact of nodal disease and a redefined RM on outcome. MATERIAL AND METHODS Retrospective analysis of pancreatic head resections for adenocarcinomas from 2003-2009. The RM was re-analysed based on tumour clearance and categorized into: histopathological evidence of a tumour; ≤ 0.5 mm, ≤ 1 mm, ≤ 1.5 mm, or ≤ 2.0 mm of the actual surgical resection margin. The impact of histopathological variables on cancer-specific survival (CSS) and disease-free survival (DFS) was analysed. RESULTS LND, LNB and LNR were independent prognostic markers for CSS (P = 0.048, 0.003, 0.016) but, did not influence DFS. A LNR < 0.143 was associated with a higher CSS [38.16 ± 4.69 versus 20.59 ± 2.20 months, P = 0.0042, hazard ratio (HR) 3.74 (95% confidence interval (CI) 1.52-9.23)]. An R1 RM was not associated with CSS or DFS on multivariate analysis, irrespective of the distance. LNB and LNR maintained independent significance irrespective of the size of the RM. CONCLUSION LNB and LNR are the only prognostic factors for CSS in patients with pancreatic head adenocarcinoma, but do not predict recurrence. Microscopic RMs does not seem to influence the outcome even when redefined. Further prospective studies are indicated to substantiate these findings.

Hepatocellular adenoma in advanced-stage fatty liver disease

Hepatocellular adenomas are defined as benign hepatocellular neoplasms occurring in otherwise near normal liver and adenomatosis as 10 or more such lesions. We present a case of a 45-year-old man with radiological adenomatosis, histologically confirmed with resection of one lesion, arising within advanced-stage nonalcoholic fatty liver disease (nearly cirrhotic). Hepatocellular adenomas have recently been divided into four categories and the lesion in the present case had morphologic and immunohistochemical features of an inflammatory hepatocellular adenoma. These findings demonstrate that, in contrast to the current dogma, nodules within advanced-stage liver disease may rarely be best classified as adenomas. This should be considered in the radiological differential diagnosis when assessing a patients suitability for transplantation.

Biological and Prognostic Significance of the Morphological Types and Vascular Patterns in Colorectal Liver Metastases (CRLM): Looking Beyond the Tumor Margin.

AbstractPatients with encapsulated colorectal liver metastases (CRLM) have a better prognosis than those without a capsule. The reason for the encapsulation is unknown. Hypoxia inducible factor-1&agr; (HIF-1&agr;) increases tumor angiogenesis and tumor tissue expression is associated with reduced survival. Our aim was to determine whether the good prognosis of encapsulated CRLM is associated with reduced HIF-1&agr; expression by the cancer.The study selected only patients who had not undergone neoadjuvant chemotherapy prior to a potentially curative hepatectomy for CRLM. From 30 selected patients, serial sections were cut from a single randomly selected metastasis. Morphology was assessed following H&E staining. Tumor hypoxia, vascular endothelial growth factor (VEGF), proliferation, and microvascular density (MVD) were assessed by immunostaining for HIF-1&agr; and carbonic anhydrase-9 (CA-9), VEGF, Ki67, and cluster of differentiation-31, respectively. MVD was calculated in the vascular hot spots. Pathology was reported without clinical outcome information. Actual long-term survival was recorded.Thirteen (43%) of the cancers were encapsulated CRLM containing glands which were large, complex, and cribriform. Thirteen (43%) were infiltrative CRLM and their glands were small, closely packed, and rounded with vessels in the interglandular fibrous tissue with no capsule; 3 (10%) had a mixed picture. Encapsulated CRLM had a higher expression of HIF-1&agr; (58% vs 8%, P = 0.03), CA-9 (42% vs 0%, P = 0.04), and VEGF (92% vs 25%, P = 0.02). MVD was lower in the encapsulated CRLM group (37 mm2 vs 143 mm2, P < 0.001). The median follow-up was 115 months. The encapsulated CRLM group had a better overall and 5-year survival (relative hazard: 0.58, P = 0.057 and hazard ratio: 0.52, P = 0.044).There are 2 main morphological appearances of CRLM which have very different long-term survival following liver resection surgery. The morphology is associated with differences in expression of HIF-1&agr;, CA-9, VEGF, and angiogenesis.

Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours

Chemotherapy (CT) is widely used for neuroendocrine tumours (NETs), but there are no validated biomarkers to predict response. The Ki-67 proliferation index has been proposed as a means of selecting patients for CT, but robust data are lacking. The aim of this study was to investigate the relationship between response to chemotherapy and Ki-67 in NET. We reviewed data from 222 NET patients treated with CT. Tumours were graded according to Ki-67 index: G1 ≤2%, G2 3-20% and G3 >20%. Response was assessed according to RECIST and survival calculated from start of chemotherapy to death. To explore Ki-67 as a marker of response, we calculated the likelihood ratio and performed receiver operating characteristic analysis. Overall, 193 patients had a documented Ki-67 index, of which 173 were also evaluable for radiological response: 10% were G1, 46% G2 and 43% G3; 46% were pancreatic NET (PNET). Median overall survival was 22.1 months. Overall response rate was 30% (39% in PNET vs 22% in non-PNET) and 43% of patients had stable disease. Response rate increased with grade: 6% in G1 tumours, 24% in G2 and 43% in G3. However, maximum likelihood ratio was 2.3 at Ki-67=35%, and the area under the ROC curve was 0.60. As reported previously, a high Ki-67 was an adverse prognostic factor for overall survival. In conclusion, response to CT increases with Ki-67 index, but Ki-67 alone is an unreliable means to select patients for CT. Improved methods to stratify patients for systemic therapy are required.

Liver transplant for adult hemophagocytic lymphohistiocytosis: case report and literature review.

We report the case of a middle-aged man who died from multiorgan failure 3 weeks after orthotopic liver transplant for fulminant hepatic failure, associated with a rare, often fatal, hematologic condition that usually presents in childhood. We discuss the importance of its diagnosis, treatment, and implications for liver transplant.

Use of molecular imaging to differentiate liver metastasis of colorectal cancer metastasis from neuroendocrine tumor origin.

Synchronous malignant neoplasms in a single patient are well documented in the literature. It is also recognized that there is increasing incidence of synchronous non-neuroendocrine neoplasm in patients with neuroendocrine tumor (NET). We present a case, of a patient with synchronous colorectal cancer and pancreatic NET, both cancers presenting with liver metastasis. By using 18F-FDG PET and 68Ga-DOTATATE PET imaging, we showed 2 different tumor types within the liver, which was subsequently confirmed on liver biopsy. This case report shows the utility of molecular imaging using different PET peptides. These newer modalities are useful in understanding the biology of the NET and in determining the best patient management.

Radiological tumor density and lymph node size correlate with survival in resectable adenocarcinoma of the pancreatic head: A retrospective cohort study.

INTRODUCTION Tumors within the pancreatic head show a variable density and enhancement on computerized tomography (CT). The relationship between the radiological appearance of pancreatic adenocarcinoma on CT and survival remains unclear. The aim of this study was to evaluate the relationship between the tumor density on CT and survival. We also evaluated the correlation between lymph node (LN) size and overall survival in patients undergoing pancreaticoduodenectomy for head of pancreas adenocarcinoma. MATERIALS AND METHODS Case records of patients undergoing pancreaticoduodenectomy for the adenocarcinoma of pancreas head, between 2005 and 2009, were evaluated. CT was interpreted to document tumor density - Hounsfield unit (HU) and LN size of enlarged LNs. Histology was analyzed to review tumor differentiation and LN status. Survival was correlated with LN size and tumor density (HU). RESULTS Increasing tumor density was significantly associated with an adverse outcome (P = 0.042, hazard ratio [HR] 1.034, 1.002-1.067 95% confidence interval [95% CI]). Patients with well-differentiated tumors had significantly lower tumor density as compared to moderately differentiated tumors (39.00 ± 26.00 vs. 71.31 ± 21.03 HU, P = 0.005). LN size more than 1 cm irrespective of LN status strongly correlated with the survival and was found to be an important prognostic factor (19.37 ± 2.71 months vs. 27.44 ± 2.74 months; P = 0.025; HR 2.70; 1.09-6.68 95% CI). CONCLUSION Increasing pancreatic tumor density and the lymph nodal size of more than 1 cm are strong predictors of unfavorable overall survival for resectable adenocarcinoma of the pancreatic head. Further studies are required to identify the value of these proposed prognostic factors.

Primary hepatic leiomyoma: unusual cause of an intrahepatic mass

Leiomyomas are benign lesions arising from the smooth muscle layer. They are most commonly detected either within the gastrointestinal or genitourinary tracts. Primary hepatic leiomyoma (PHL) is a rare pathology. It is an isolated pathology within the liver, without evidence of any other coexisting leiomyomas. Very few cases have been described in literature. PHL may occur in healthy individuals although an association with immunodeficiency and Epstein-Barr virus (EBV) infection has been observed. Majority of the reported cases have been in females. A 20-year-old female patient presented with abdominal symptoms. MRI confirmed an 8 cm mass, with very low signal intensity on T2 images and peripheral rim enhancement on gadolinium. A laparoscopic left lateral sectorectomy was performed. Final histopathology confirmed the presence of benign lesion with spindle cell and smooth muscle proliferation and a fibro-vascular stroma compatible with a leiomyoma. There was no evidence of any leiomyomatous lesion elsewhere in the body. A rare diagnosis of PHL was therefore established. Acknowledging the rare incidence of this lesion, we report the same and review the relevant literature. PHL is usually a retrospective diagnosis, confirmed on histo-pathology assessment of the resected specimen. Liver resection is required in these patients due to the presence of symptoms, in the presence of a solid mass lesion within the liver. Surgery is thus definitive, diagnostic cum therapeutic.

Evaluation of clinical prognostic factors and further delineation of the effect of mesenteric fibrosis on survival in advanced midgut neuroendocrine tumours

Background: Small intestinal neuroendocrine tumours (SI NETs) represent 30–50% of small bowel neoplasms and often present at an advanced stage. To date, there is relatively limited literature regarding prognostic factors affecting overall survival (OS) in stage IV disease. In addition, the prevalence of mesenteric fibrosis (MF) in SI NETs and its effect on OS have not been sufficiently explored in the literature. Aim: The primary aim of this study was to perform a large-scale survival analysis in an institutional cohort of 387 patients with metastatic (stage IV) SI NETs. The secondary aim was to provide epidemiological information regarding the prevalence of MF and to evaluate its effect on OS. Results: The median OS was 101 months (95% CI 84, 118). Age > 65 years, mesenteric metastases with and without desmoplasia, liver metastases, carcinoid heart disease (CHD) and bone metastases were associated with a significantly shorter OS, while primary tumour resection was predictive of a longer OS. The benefit of surgical resection was limited to symptomatic patients. MF was present in approximately 50% of patients with mesenteric lymphadenopathy. Elevated urinary 5-HIAA levels correlated strongly with the presence of CHD (p < 0.001) and to a lesser extent (p = 0.02) with MF. MF and CHD did not usually co-exist, suggesting that different mechanisms are likely to be involved in the development of these fibrotic complications. Conclusions: This study has identified specific prognostic factors in a large cohort of 387 patients with advanced SI NETs and has provided useful epidemiological data regarding carcinoid-related fibrotic complications.