Daniel Ansari

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis. There is a need to identify prognostic subtypes of PDAC to predict clinical and therapeutic outcomes accurately, and define novel therapeutic targets. The purpose of this review was to provide a systematic summary and review of available data on immunohistochemical (IHC) prognostic and predictive markers in patients with PDAC.

Pancreatic Cancer: The Role of Pancreatic Stellate Cells in Tumor Progression

Pancreatic ductal adenocarcinoma is an aggressive and highly lethal disease frequently characterized by a dense stromal or desmoplastic response. Accumulating evidence exists that tumor desmoplasia plays a central role in disease progression and that e.g. activated pancreatic stellate cells (PSCs) are responsible for the excess matrix production. The mechanisms underlying the tumor versus stroma interplay are complex. Pancreatic cancer cells release mitogenic and fibrogenic stimulants, such as transforming growth factor β1, platelet-derived growth factor (PDGF), sonic hedgehog, galectin 3, endothelin 1 and serine protease inhibitor nexin 2, all of which may promote the activated PSC phenotype. Stellate cells in turn secrete various factors, including PDGF, stromal-derived factor 1, epidermal growth factor, insulin-like growth factor 1, fibroblast growth factor, secreted protein acidic and rich in cysteine, matrix metalloproteinases, small leucine-rich proteoglycans, periostin and collagen type I that mediate effects on tumor growth, invasion, metastasis and resistance to chemotherapy. This review intends to shed light on the mechanisms by which PSCs in the stroma influence pancreatic cancer development. The increased understanding of this interaction will be of potential value in designing new modalities of targeted therapy.

Fast-track surgery: procedure-specific aspects and future direction

IntroductionFast-track (FT) surgery can be defined as a coordinated perioperative approach aimed at reducing surgical stress and facilitating postoperative recovery. The objective of this review was to examine the literature on the procedure-specific application of FT surgery.DiscussionThe concept of FT rehabilitation has been applied mainly in colorectal surgery, but positive data have appeared also in other areas such as orthopedic, hepatopancreaticobiliary, urological, upper gastrointestinal, gynecological, thoracic, vascular, endocrine, breast, and pediatric surgeries. There is very little experience with comprehensive FT programs in cardiac surgery or trauma. Quantitative analysis from randomized trials and cohort studies suggest that FT is effective in reducing hospital stay without increased adverse events. Other benefits of the FT approach include a reduction in complications, ileus, fatigue, pain, and hospital expenses. However, despite clear benefits of FT care, implementation in daily practice has been slow. Further efforts must be undertaken to secure implementation in routine clinical practice. Standardized FT protocols should be provided on a procedure-specific basis.

hENT1 expression is predictive of gemcitabine outcome in pancreatic cancer: A systematic review

High human equilibrative nucleoside transporter 1 (hENT1)-expression has shown a survival benefit in pancreatic cancer patients treated with gemcitabine in several studies. The aim of this systematic review was to summarize the results and try to assess the predictive value of hENT1 for determining gemcitabine outcome in pancreatic cancer. Relevant articles were obtained from PubMed, Embase and Cochrane databases. Studies evaluating hENT1-expression in pancreatic tumor cells from patients treated with gemcitabine were selected. Outcome measures were overall survival, disease-free survival (DFS), toxicity and response rate. The database searches identified 10 studies that met the eligibility criteria, and a total of 855 patients were included. Nine of 10 studies showed a statistically significant longer overall survival in univariate analyses in patients with high hENT1-expression compared to those with low expression. In the 7 studies that reported DFS as an outcome measure, 6 had statistically longer DFS in the high hENT1 groups. Both toxicity and response rate were reported in only 2 articles and it was therefore hard to draw any major conclusions. This review provides evidence that hENT1 is a predictive marker for pancreatic cancer patients treated with gemcitabine. Some limitations of the review have to be taken into consideration, the majority of the included studies had a retrospective design, and there was no standardized scoring protocol for hENT1-expression.

SPARC: A Potential Prognostic and Therapeutic Target in Pancreatic Cancer.

Abstract Pancreatic cancer is a complex and heterogeneous disease that often lacks disease-specific symptoms in early stages. The malignancy is currently the fourth leading cause of cancer-related death in Western countries. In advanced stages, the overall 5-year survival is less than 1% to 2%. Most available treatments lack convincing cost-efficiency determinations and are generally not associated with relevant success rates. Targeting stromal components and stromal depletion is currently becoming an area of extensive research in pancreatic cancer. In this context, a glycoprotein, SPARC (secreted protein acidic and rich in cysteine) appears to play a central role. Still, the role of SPARC in carcinogenesis is controversial because conflicting results have been reported, and the pathways involved in SPARC signaling are not well established. Nonetheless, SPARC is highly expressed in the tumor stroma, principally in peritumoral fibroblasts, and the overexpression of SPARC in this compartment is associated with poorer prognosis. Interestingly, it has been suggested that SPARC present in the tumor stroma could sequester albumin-bound paclitaxel, enhancing the delivery of paclitaxel into the tumor microenvironment. In the present review, we summarize the known associations between SPARC and pancreatic cancer. Moreover, present and future therapies comprising SPARC-targeting are discussed.

Radiofrequency ablation or percutaneous ethanol injection for the treatment of liver tumors

The liver is a common location of both primary and secondary malignancies. For unresectable liver cancer, many local ablative therapies have been developed. These include e.g., percutaneous ethanol injection (PEI), percutaneous acetic acid injection, radiofrequency ablation (RFA), cryoablation, microwave ablation, laser-induced thermotherapy, and high-intensity focused ultrasound. RFA has recently gained interest and is the most widely applied thermoablative technique. RFA allows more effective tumor control in fewer treatment sessions compared with PEI, but with a higher rate of complications. However, there are certain circumstances where PEI therapy represents a better strategy to control liver tumors than RFA, especially in situations where RFA is difficult, for example when large vessels surround the tumor. In the context of hepatocellular carcinoma (HCC), both RFA and PEI are feasible and of benefit in non-operable patients. RFA seems superior to PEI in HCC > 2 cm, and the combination of interventions may be of benefit in selected patients. Liver resection is superior to RFA for patients with HCC meeting the Milan criteria, but RFA can be employed in tumors ≤ 3 cm and where there is an increased expected operative mortality. In addition, some lines of evidence indicate that RFA and PEI can be employed as a bridge to liver transplantation. The use of RFA in colorectal liver metastases is currently limited to unresectable disease and for patients unfit for surgery. The aim of this article is to summarize the current status of RFA in the management of liver tumors and compare it to the cheap and readily available technique of PEI.

Major haemorrhagic complications of acute pancreatitis.

Haemorrhage is a rare, potentially fatal complication in acute pancreatitis (AP). The aim was to investigate the incidence, management and outcome related to this complication.

Artificial neural networks predict survival from pancreatic cancer after radical surgery

BACKGROUND Artificial neural networks (ANNs) are nonlinear pattern recognition techniques that can be used as a tool in medical decision making. The objective of this study was to develop an ANN model for predicting survival in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS A flexible nonlinear survival model based on ANNs was designed by using clinical and histopathological data from 84 patients who underwent resection for PDAC. RESULTS Seven of 33 potential risk variables were selected to construct the ANN, including lymph node metastasis, differentiation, body mass index, age, resection margin status, peritumoral inflammation, and American Society of Anesthesiologists grade. Three variables (ie, lymph node metastasis, leukocyte count, and tumor location) were significant according to Cox regression analysis. Harrells concordance index for the ANN model was .79, and for Cox regression it was .67. CONCLUSIONS For the first time, ANNs have been used to successfully predict individual long-term survival for patients after radical surgery for PDAC.

Fast-track programmes for hepatopancreatic resections: where do we stand?

BACKGROUND Fast-track (FT) programmes represent a series of multimodal concepts that may reduce surgical stress and speed up convalescence after surgery. The aim of this systematic review was to evaluate FT programmes for patients undergoing hepatopancreatic surgery. METHODS PubMed, Embase and the Cochrane Library databases were searched for studies of FT vs. conventional recovery strategies for liver and pancreatic resections. RESULTS For liver surgery, three cohort studies were included. Primary hospital stay was significantly reduced after FT care in two of the three studies. There were no significant differences in rates of readmission, morbidity and mortality. For pancreatic surgery, three cohort studies and one case-control study were included. Primary hospital stay was significantly shorter after FT care in three out of the four studies. One study reported a significantly decreased readmission rate (7% vs. 25%; P= 0.027), and another study showed lower morbidity (47.2% vs. 58.7%; P < 0.01) in favour of the FT group. There was no difference in mortality between the FT and control groups. CONCLUSIONS FT rehabilitation for liver and pancreatic surgical patients is feasible. Future investigation should focus on optimizing individual elements of the FT programme within the context of liver and pancreatic surgery.

Pancreatic cancer : Yesterday, today and tomorrow

Pancreatic cancer is one of our most lethal malignancies. Despite substantial improvements in the survival rates for other major cancer forms, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Pancreatic cancer is usually detected at an advanced stage and most treatment regimens are ineffective, contributing to the poor overall prognosis. Herein, we review the current understanding of pancreatic cancer, focusing on central aspects of disease management from radiology, surgery and pathology to oncology.