Recent Developments in Surgery Minimally Invasive Approaches for Patients Requiring Pancreaticoduodenectomy

Over the past decade, minimally invasive surgery has been introduced as a means to allow manipulation of delicate tissues with outstanding visualization of the surgical field. The purpose of this article is to review the available literature regarding early postoperative outcomes and the technical challenges of minimally invasive pancreaticoduodenectomy, including robotic techniques. Herein, we provide a retrospective review of all published studies in the English literature in which a minimally invasive pancreaticoduodenectomy was performed. The reported advantages of minimally invasive pancreaticoduodenectomy include better visualization, faster recovery time, and decreased length of hospital stay. In cases of robotic approaches, some of the proposed advantages include increased dexterity and a superior ergonomic position for the operating surgeon. To our knowledge, few studies have reported results comparable to open techniques in oncologic outcomes with regard to the number of lymph nodes resected and clear margins obtained. An increasing number of pancreatic resections are being performed using minimally invasive approaches. It remains to be determined if the benefits of this technique outweigh its longer operative times and higher costs

Beyond Cytology. Why And When Does The Oncologist Require Core Tissue?

There are 2 main reasons why oncologists may require additional tissue and a histologic section in addition to cytopathology from FNA specimens: improved diagnostic accuracy and molecular characterization of tumors. Rather than mutually exclusive diagnostic procedures, EUS-FNA and EUS-CNB must be viewed as supplementary techniques and both approaches should be incorporated as essential tools in the current endoscopic armamentarium. © 2014 Elsevier Inc

Development and Histopathological Characterization of Tumorgraft Models of Pancreatic Ductal Adenocarcinoma

<div><p>Pancreatic cancer is the one of the deadliest of all malignancies. The five year survival rate for patients with this disease is 3-5%. Thus, there is a compelling need for novel therapeutic strategies to improve the clinical outcome for patients with pancreatic cancer.  Several groups have demonstrated for other types of solid tumors that early passage human tumor xenograft models can be used to define some genetic and molecular characteristics of specific human tumors. Published studies also suggest that murine tumorgraft models (early passage xenografts derived from direct implantation of primary tumor specimens) may be useful in identifying compounds with efficacy against specific tumor types.  Because pancreatic cancer is a fatal disease and few well-characterized model systems are available for translational research, we developed and characterized a panel of pancreatic tumorgraft models for biological evaluation and therapeutic drug testing.  Of the 41 primary tumor specimens implanted subcutaneously into mice, 35 produced viable tumorgraft models.  We document the fidelity of histological and morphological characteristics and of KRAS mutation status among primary (F0), F1, and F2 tumors for the twenty models that have progressed to the F3 generation.  Importantly, our procedures produced a take rate of 85%, higher than any reported in the literature. Primary tumor specimens that failed to produce tumorgrafts were those that either contained <10% tumor cells or that were obtained from significantly smaller primary tumors. In view of the fidelity of characteristics of primary tumor specimens through at least the F2 generation in mice, we propose that these tumorgraft models represent a useful tool for identifying critical characteristics of pancreatic tumors and for evaluating potential therapies.  </p> </div

ErbB3 expression promotes tumorigenesis in pancreatic adenocarcinoma

Historically, ErbB3 has been overlooked within the ErbB receptor family due to its perceived lack of tyrosine kinase activity. We have previously demonstrated that in pancreatic cancer ErbB3 is the preferred dimerization partner of EGFR, ErbB3 protein expression level directly correlates with the anti-proliferative effect of erlotinib (an EGFR-specific tyrosine kinase inhibitor), and transient knockdown of ErbB3 expression results in acquired resistance to EGFR-targeted therapy. In this study, we develop a stable isogenic model of ErbB3 expression in an attempt to decipher ErbB3's true contribution to pancreatic cancer tumorigenesis and to examine how this receptor affects cellular sensitivity to EGFR-targeted therapy. Analysis of the EGFR-ErbB3 heterodimer demonstrates that ligand-induced PI3K-AKT signaling is limited to ErbB3-expressing cells and that this signaling cascade can be partially abrogated by inhibiting EGFR function with erlotinib. Using our model of exogenous ErbB3 expression we showed a direct relationship between ErbB3 protein levels and increased pancreatic cancer cell proliferation in vitro. In vivo, ErbB3+PANC-1 xenografts had a significantly larger tumor volume than PANC-1 control xenografts (ErbB3-PANC-1) and displayed increased sensitivity to EGFR-targeted therapy. In pancreatic cancer, ErbB3 appears to be critically involved in EGFR signaling as evidenced by its profound effect on cellular proliferation and its ability to influence response to EGFR-targeted therapy

Three generations of tumorgraft UAB-PA2 retain morphology similar to that of the primary tumor.

<p>UAB-PA2 tumor was serially passaged to the third generation (F3), and the morphology of H&E stained sections of tumors compared. The Results section contains details of histological analyses. </p

Beyond Cytology

There are 2 main reasons why oncologists may require additional tissue and a histologic section in addition to cytopathology from FNA specimens: improved diagnostic accuracy and molecular characterization of tumors. Rather than mutually exclusive diagnostic procedures, EUS-FNA and EUS-CNB must be viewed as supplementary techniques and both approaches should be incorporated as essential tools in the current endoscopic armamentarium. © 2014 Elsevier Inc

Mutations in codon 12 of the KRAS gene of all twenty primary PDAC tumors (F0) were conserved in the F1 and F2 tumorgrafts derived from each tumor.

<p>Electropherograms for eight tumors are shown in this Figure; results for an additional six tumors are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0078183#pone.0078183.s001" target="_blank">Figure S1</a>; results from all twenty F0, F1 and F2 tumors are summarized in Table 3. (<b>a</b>) The normal sequence of codon 12 from normal human pancreas DNA (wild type; WT) is GGT (encoding glycine [G]) as shown in the box. (<b>b</b>) Representative PCR results using a primer set that anneals to human, but not murine, KRAS sequences. UAB-PA3: NP (normal pancreas), F0 (primary tumor), and F1 and F2 tumorgrafts show readily detectable bands (214 base pairs). Mouse NP (normal pancreas) and negative control (cont [-]) lanes showed no bands. Experimental details are in Methods section. (<b>c</b>) Electropherograms show mutations in codon 12 of the KRAS gene in eight primary PDAC tumors (F0) and in the F1 and F2 tumorgrafts derived from each tumor. </p