Conduct of anaesthesia

The primary goals of general anesthesia are to maintain the health of the patient while providing amnesia, hypnosis (lack of awareness), analgesia and immobility. Secondary goals may vary depending on the patient's medical condition and the surgical procedure. Perioperative planning involves the integration of preoperative, intraoperative and postoperative care. Flexibility, the ability to anticipate problems before they occur and the ability to execute contingency plans are skills that define...

Anaesthetic management

General anesthesia with mechanical ventilation is the rule. Spinal anesthesia is impractical owing to the length of the operation. However, epidural analgesia could, in theory, be used as the sole anesthetic technique. It's our belief that the length of surgery, insertion of central lines and the high likelihood of conversion to general anesthesia make epidural alone unsatisfactory. Epidural analgesia may be beneficial post-operatively in reducing venous thromboembolic events, the incidence of...

Clinical manifestation

When functional, PNETs can be characterized by the type of hormone secreted leading to a specific clinical manifestation (Table 2). Specific details about some common tumors, based on the presentation are discussed below. Insulinomas are the most common PNET, comprising 30-40 of these tumors. Overall, they remain a rare entity with an incidence of approximately 0.4 100,000 patient years (Mathur et al., 2009).Classically, they present with Whipple's Triad a combination of symptoms of...

Combination chemotherapy Nongemcitabine containing regimens

An earlier non-gemcitabine containing regimen of irinotecan and docetaxel was examined in a phase II study randomising patients into two arms with or without cetuximab but response rates were 7 and 4.5 respectively. This did not meet a pre-determined goal to proceed to a phase III study. P81 The recent French PRODIGE 4 (ACCORD 11) study 29) randomised 342 patients with metastatic pancreatic carcinoma, who had an Eastern Cooperative Oncology Group performance status score of 0 or 1, to either a...

Combination chemotherapy

Although the benefit of chemotherapy in patients with advanced pancreatic cancer is well established, the magnitude of the effect is rather small, with an absolute improvement of survival at 5 years of 3 to 6 (survival rates from 1975-77 to 1999-2005) (Oberstein & Saif, 2011). Over the past decade, multiple randomized trials have been performed to assess a number of gemcitabine-combination chemotherapy regimens in an effort to improve these modest results. These have included combinations...

Operative findings

Earlier on approximately 80 of patients would have had a surgical laparotomy after imaging studies and in a third of those only a biopsy would have been feasible. Half of those operated on would have had a biliary bypass performed and some of those also a gastric bypass with 5-10 undergoing only a gastric bypass (Brooks 1976). Now laparoscopy is increasingly used to stage the extent of disease and obtain a biopsy (Nagorney 1999). Either method would reveal that in 2 3 of established cases the...

Passive immunotherapy

Passive immunotherapy could be accomplished by infusion monoantibody and tumor specific T-cell which was actived in vitro. With advances in structural and functional genomics, recent work has focused on targeted molecular therapy using monoclonal antibodies. Many monoantibodies were used to target molecules on the tumor cell surface and normal tissue stroma, which are related to pancreatic cancer oncogenesis, tumor growth or resistance to chemotherapy, as well as molecules involved in...

Cancer immunotherapy protocols

Clinical trials using various immunotherapies, active immunization with tumor antigens, or tumor cell-derived products, and adoptive immunotherapy using antitumor immune cells were conducted in various cancers, most extensively in melanoma, and tumor regression was observed in some patients. Active Immunization Immunizations with synthetic peptides, particularly MHC class I-binding epitopes, were performed in various trials. Since native epitopes have relatively low immunogenicity, various...

Immune surveillance and tumour evasion

The extraordinary features of the immune system make it possible to discern self from non-self. However, most human cancers, and pancreatic cancer in particular, are known to be poorly immunogenic, as crucial somatic genetic mutations can generate pancreatic cancer proteins that are essentially altered self proteins. Furthermore, promising immunotherapeutic approaches that have been used for relatively immunogenic cancers such as melanoma have met with variable success6. These observations have...

Immune escape and immunosuppression

In the past 50 years, with the advances in cellular, molecular biology of cancer and development of immunology, people comes to realizes the relationship between tumor and immune cells is just like a cat and mouse game. The human immune system assume the responsibility to get rid of the extrinsic and endogenic abnormal antigen, it can produce actived immunocyte or immune material such as antibody to react anomalous antigen and finally eliminate the target, but the fact is not under our desire....

Immune target and Immune response in pancreatic cancer

Cancer is fundamentally a gene associated disease, it has become increasingly clear that some genomic instability and aberrant gene expression lead to biologic behaviour abnormality in tumor cells. In pancreatic cancer, Several genes have high mutation rate in different phase, so the tumor cell may express abnormal antigens that make them immunologically distinct and potential targets for the host immune system. K-Ras The mutation of K-ras oncogene (homologous to the ras gene of Kirsten murine...

New immunotherapy targets

The inability of previously tested antigens (including CEA, KRAS, MUC1 and gastrin) to induce immune-specific responses underscores the challenge to identify more relevant immunogenic targets. Indeed, these antigens were chosen only because they were overexpressed or had altered expression in pancreatic tumours, and not because they had been shown to be immunogenic. Therefore, there might be additional as-yet-unidentified antigens that might be more immunogenic for inducing effective immunity...

Allogeneic antigenspecific immunotherapy

Allogeneic antigen-specific immunotherapies, nonmyeloablative SCT (minitransplant) and DLI (donor leukocyte infusion), are reported to have some antitumor effect graft versus tumor (GVT) on solid tumors, including RCC, breast cancer, and pancreatic cancer, in addition to haematological malignancies.110GVT effects were also observed in pancreatic cancer patients in minitransplant protocols conducted in Japan. Although the mechanisms of the antitumor effects, such as allogeneic responses to minor...

Adoptive Immunotherapy with antitumor 41 Immune cells

Passive immunotherapy with large doses of activated antitumor lymphocytes was also employed since there was a possibility that active immunization would be insufficient to induce enough of an immune response to cause tumor regression in the immunosuppressed patient with a large tumor burden. Adoptive transfer of tumor-reactive T cells cultured from tumor-infiltrating lymphocytes, along with IL-2, resulted in a clinical response in melanoma patients.65 Adoptive transfer of EBV-specific T cells...

Systems and Network Centric Understanding of Pancreatic Ductal Adenocarcinoma Signalling

Mohammad, Fazlul H. Sarkar and Asfar S. Azmi Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is intractable to currently available treatment modalities (Vincent et al. 2011). Failure of standard chemo-, radio- and neoadjuvant single pathway targeted therapies indicate that before newer treatment regimens are designed, one has to re-visit the basic understanding of the origins and complexity of PDAC. As such, PDAC is now appreciated to have not only a...

Intech

Free online editions of InTech Books and Journals can be found at www.intechopen.com Chapter 1 The Genetics of Pancreatic Cancer 1 Dagan Efrat and Gershoni-Baruch Ruth Chapter 2 Systems and Network-Centric Understanding of Pancreatic Ductal Adenocarcinoma Signalling 15 Irfana Muqbil, Ramzi M. Mohammad, Fazlul H. Sarkar and Asfar S. Azmi Chapter 3 Novel Biomarkers in Pancreatic Cancer 31 Simona O. Dima, Cristiana Tanase, Radu Albulescu, Anca Botezatu and Irinel Popescu Chapter 4 Medical Therapy...

CNCTL 15mm

FNA of a lymph node found during diagnostic EUS in 59 year-old male with metastatic pancreatic adenocarcinoma. Radial and curve linear array echoendoscopes are available for EUS. Radial echoendoscopes provide a circumferential view at right angle to the shaft of the scope, similar to those provided by CT. The linear array echoendoscope generates longitudinal sector images parallel to the axis of the endoscope giving a 120 to 180 scanning view. The linear echoendoscope also has an...

Biologically targeted therapies

Recently, a number of studies have demonstrated activity in PNETs, targeting the vascular endothelial growth factor (VEGF) signaling and the mammalian target of rapamycin (mTOR) pathways. Although, obejective responses have been persistently low across studies, improvements in progression free survival have been encouraging. PNETs are characterized by upregulation of VEGF and VEGF receptor (VEGFR). This correlates with increased angiogenesis, metastases and can potentially lead to decreased...

Therapeutic Interventions

Wolf Reflecton Water

Endoscopy has no role in the treatment of pancreatic cancer, as the only definite treatment is surgical resection when the disease is diagnosed in early stages. For advanced cases, palliation is indicated and endoscopy plays an important role. The procedures currently performed for palliation of pancreatic cancer involve stent placement for the drainage of biliary or pancreatic duct obstruction by ERCP or under EUS guidance, celiac plexus neurolysis (CPN), injection of anti-tumor agents, and...

Histology

About 80 of pancreatic malignancies are ductal adenocarcinomas, of which approximately 70 occur in the head of the pancreas. A variety of uncommon types of pancreatic carcinoma have been described, including acinar, adenosquamous, anaplastic, papillary, mucinous and microadenocarcinomas, each of which composes less than 5 of the total. All of these have similarly poor prognoses and are treated in a similar fashion. Also uncommon are mucinous cystic neoplasms (cystadenoma cystadenocarcinoma) of...

L node

The picture demonstrates one of the multiple peri-pancreatic lymph nodes found in a patient with metastatic pancreatic adenocarcinoma. The largest measured 25mm. FNA of the lymph node was performed and cytology was consistent with poorly differentiated adenocarcinoma. the cystic fluid CEA (using a cutoff value of 192 ng mL) was able to differentiate mucinous vs. nonmucinous cystic lesions with an accuracy of 79 , which was significantly higher than the accuracy of EUS morphology (51 )...

Chemotherapy for locally advanced and metastatic disease

The primary goals of treatment for advanced pancreatic cancer are palliation and improved survival. Although some effect on survival may be achieved, these benefits are usually limited to patients with adequate performance status (ECIG 0-2). Patients who present with very poor performance status may benefit from the administration of Gemcitabine, but comfort-directed measures are always paramount. Before initiating cytotoxic therapy, an open dialogue regarding the goals of treatment should take...

References

Adsay NV, Adea A, Basturk O, Kilnc N, Nassar H, Cheng JD. Secondary tumours of the pancreas An analisys of a surgical and autopsy database and review of the literature. Virchows Arch 2004 444 527-35. American Cancer Society. (2002) Facts and figures. Atlanta, GA American Cancer Society. Amin Z, Theis B, Russel RC, et al (2006) Diagnosing pancreatic cancer the role of percutaneous biopsy and Ct. Clin Radiol 61 996-1002 Arcari A, Anselmi E, Bernuzzi P, et al (2005). Primary pancreatic lymphoma....

Novel Biomarkers in Pancreatic Cancer

Dima1, Cristiana Tanase2, Radu Albulescu2, Anca Botezatu3 and Irinel Popescu1 1Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute of Digestive Disease and Liver Transplantation, Bucharest, 2Biochemistry and Proteomics Department, Victor Babes National Institute of Pathology, Bucharest, 3Viral Genetic Engineering Laboratory, Romanian Academy 'Stefan S. Nicolau' Virology Institute, Bucharest, Pancreatic ductal adenocarcinoma( PDAC) cancer is one of the most...

Antibody

Monoclonal antibodies against human tumor targets were initially in rodents, which will induce immunologic responses from patient against mouse antibodies. With the drvelopment of recombinant DNA technology, this problem was solved and chimeric antibodies, antibody fragments or intact fully human antibodies were produced and tested clinically. Base on moral principles, antibodies were used as adjunctive treement with chemotherapy agents, small molecule signal transduction inhibitors, or...

The Genetics of Pancreatic Cancer

Dagan Efrat12 and Gershoni-Baruch Ruth13 institute of Human Genetics, Rambam Health Care Campus, Haifa, 2Department of Nursing, the Faculty of Social Welfare and Health Sciences, University of Haifa, 3The Ruth and Bruce Rapoport Faculty of Medicine, Technion-Institute of Technology, Haifa, Globally, pancreatic cancer is considered a rare cause of cancer. More than 250,000 new cases, equivalent to 2.5 of all forms of cancer, were diagnosed in 2008 worldwide (Ferlay et al., 2008, 2010)....

Fh

Immune system From Robert A. Weinberg, The Biology of Cancer. 2007 At the genesis of the cancer, under ideal condition, the innate immune system responds to danger signals, macrophages and fibroblasts are enlisted to construct the microenvironment surrounding the cancer cell, just like inflmmation, many cytokines and growth factors are produced to activate innate effector cells with antitumor activity, stimulate professional antigen-presenting cells (APCs, mainly dendritic cell) to...

The ras pathway

K-ras is part of the Ras group of genes, which code for GTP-binding proteins in the cellular membrane. Ras is important in cellular differentiation and proliferation, as well as adhesion and the regulation of apoptosis. When activated by the associated EGFR, Ras leads to further downstream activation of Raf, MAP2K, MAPK and PI3K-Akt cascades. K-ras mutations lead to cell-cycle progression, and promote tumour cell survival. Mutated K-ras, seen in over 90 of pancreatic cancer is mostly identified...

Neural invasion as part of pancreatic neuropathy in PCa

The pancreas is one of the most densely innervated visceral organs(Bradley& Bem, 2003). The extrinsic component of its innervation is composed of nerve fibers running within the vagal and splanchnic nerves which originate from vagal nuclei or DRGs, respectively. Like the intestine, it also has an intrinsic innervation which is represented by intrapancreatic neurons. Importantly, enteric and intrapancreatic neurons are embryologically closely related intrapancreatic neurons develop from a...

Nonspecific immunotherapy Innate Immune system and cytokine

Nature kill cells are the central component of the innate immunity and play an important role in cancer immunosurveilance. It has been reported that NK cells can recognize and control tumor growth by direct cellular cytotoxicity and secrete immunostimulatory cytokines such as IFN-y. The further researches have demonstrated NK cells can eliminate tumor cell by inhibiting cellular proliferation, angiogenesis, promoting apoptosis and stimulate the adaptive immune system. In mouse experimental...

Adoptive cell transfer

In cellular antitumor immunity, T-cells must first be activated by bone marrow derived APCs that present tumor antigens and provide essential co-stimulatory signals, migrate and gain access to the tumor microenvironment, and overcome obstacles to effective triggering posed by the tumor. Dendritic cells, which are the strongest antigen presenting cells in the body. Their generation for anti-tumor immunity has been the focus of a vast array of scientific and clinical studies. DC's specialized...

Transforming growth factorp Tgfp Smad4 MET and IGF1

TGF-P binds to cell receptors that lead to downstream activation of SMAD4 which in turn moves into the cell nucleus to activate gene transcription. TGF-P is also involved with activating other pathways including Ras, PI3K and MAPK. Although tumour suppressive in epithelial cells, it is also involved in mediating invasion and metastasis. In pancreatic cancer, mutations in SMAD4 are seen in 50 and up to 4 of TGFp receptors. 91 Mutations of the former can lead to reduced TGF-P tumour suppression...

Active immunotherapy

Vaccine The development of human therapeutic cancer vaccines has come a long way since the discovery of major histocompatability complex (MHC) restricted tumor antigens. As an new method to reconsituting immunity, cancer vaccionation can actively harness the intrinsic power of the immne system to recognize and destroy tumors. The ideal designed vaccine should actively generate antigen-specific immune response to abnomal protein expressed in tumor cells, including activating distinct components...

Introduction

Pancreatic cancer (PCa) as one of the most aggressive malignancies of mankind has an unparallelled propensity to invade intrapancreatic nerves. This neural invasion is therefore one of the most frequent routes of spread in PCa in addition to lymphatic and vascular paths. The major clinical relevance of neural invasion (NI) has triggered intense research efforts to understand its pathomechanims, and the findings derived from all these studies show how multi-faceted this peculiar route of cancer...

Patient with jaundice

Jaundice results from an abnormally high bilirubin in the blood whose origin may be difficulty in eliminating it's then an obstructive jaundice. This is the most symptom in patients with periampullary cancer (located near the Vater's ampulla) or cancer of the pancreatic head. It can be considered a risk factor for postoperative complications. 8, 9 Many studies demonstrate that it could be associated with a higher incidence of insufficient postoperative renal function, but also of sepsis,...

Biomarkers in pancreatic cancer

In contrast to other solid tumour malignancies, there have been relatively modest or poor responses achieved with molecularly targeted agents to date in unselected patients with pancreatic cancer. There is an urgent need for a personalised approach to better define biomarkers in order to predict patients that are more likely to benefit from a particular cytotoxic or molecular targeted therapy. The biomarker with the most preclinical and clinical evidence is human equilibrative nucleoside...

Diabetes

Nearly 80 of PC patients have either frank diabetes or impaired glucose tolerance. Diabetes is usually diagnosed either concomitantly or during the two years preceding the diagnosis (Gullo et al. 1994 Permet et al. 1993). The link between abnormal glucose and PC exists only for type II diabetes. Better glycaemic control in diabetic patients undergoing major surgery has been shown to improve perioperative mortality and morbidity. Diabetics are at increased risk of myocardial ischaemia,...

Diagnosis of pancreatic neoplasia

Currently, imaging modalities for detection of pancreatic masses include ultrasonography (US), computed tomography (CT) scan, magnetic resonance imaging (MRI) magnetic resonance cholangiopancreatography, endoscopic ultrasonography (EUS). In clinical practice differential diagnosis of pancreatic masses is frequently a clinical challenge often therapeutic decision in this context is mainly based on the ability to perform a diagnosis of malignancy or to exclude malignancy (Tamm & Charnsangavej,...

Pain and inoperable pancreatic cancer

Pancreatic diseases such as cancer can cause clinically significant pain in the upper abdomen, which may radiate to the back. Pain management for pancreatic cancer patients is one of the most important aspects of their care, as it is one of the most weakening symptoms. The best therapy involves adequate therapy with constant assessment. The current management of pancreatic pain follows the WHO three-step ladder for pain control, starting with non-opioid analgesics such as nonsteroidal...

Summary and conclusion

Neural invasion in PCa bears a unique importance in the biology of this disease due its impact on patient survival, local tumor reccurence and neuropathic pain sensation. Higher interest in NI has paved path for increased research on the biology of NI and accelarated the development of numerous experimental models. The discussed in vitro and in vivo models which shall help to eludicate the pathomechanisms of NI in PCa may provide novel tools to control and to reduce NI in this highly aggressive...

Vaccines against pancreatic tumour antigens

To develop the ideal vaccine for pancreatic cancer, the following wish list would probably need to be fulfilled. First, specific cell-surface proteins must be identified that are that are crucial in the cancer growth or progression pathway and are unique to pancreatic cancer tumours. Second, these tumour-exclusive proteins should be shown to elicit a vigorous tumour-protein-specific immune response. Third, the best carrier to deliver the appropriate immunogenic tumour proteins should be...

Epidural anaesthesia analgesia

The epidural space is surrounded by the outer surface of the dura mater and the bony and ligamentous walls of the spinal canal and extends from the foramen magnum to the sacral hiatus. The cross-sectional area of the epidural space becomes smaller cranially, as the theca and its contents tend to occupy a greater proportion of space. Hence, a given volume of drugs affects a greater number of segments the more cranially it is introduced. The epidural space contains nerve roots, fat, spinal...

Why are pancreatic cancer cells attracted to nerves Molecular mechanisms of neural invasion in PCa

Neural Control Lymph Vessels

Researchers and clinicians have long puzzled about why PCa cells are frequently encountered around intrapancreatic nerves. Early reports had claimed that PCa cells enter nerves through the perineurium at its weakest points, i.e. along neural lymph vessels(di Mola& di Sebastiano, 2008), which, however, could not be confirmed in later studies. In later studies, investigators suggested that PCa cells grow along the path of least resistance after entering nerves, which was thought to be the...