Preface

Chapter 7 **Pancreatic Resections for Metastatic Disease 131**

Chapter 8 **Drug Discovery from Natural Products for Pancreatic Cancer 153**

Chapter 9 **Neoadjuvant Treatment for Nonmetastatic**

Vicente

**VI** Contents

**Section 3 Neoadjuvant Treatment 177**

**Pancreatic Cancer 179**

Mauricio Mahave Caceres

**Pancreatic Cancer 195**

Nicolae Bacalbasa, Simona Dima and Irinel Popescu

Maria C. Ramos, Olga Genilloud, Fernando Reyes and Francisca

Christian Caglevic Medina, Sergio Panay Serra, Carlos Gallardo Araneda A, Jaime Anabalon Toha, Elizabeth Milla Ramirez and

Laura Antolino, Paolo Aurello, Federico Todde, Silvia Amato, Niccolò Petrucciani, Andrea Kazemi Nava, Giuseppe Nigri, Stefano

Valabrega, Giovanni Ramacciato and Francesco D'Angelo

Chapter 10 **The Role of Neoadjuvant Therapy in Surgical Treatment of**

It is a great pleasure and honor for me to present this interesting book about pancreatic can‐ cer, which has been written by an international group of experts, medical doctors, university professors, and basic researchers, all of them are actively working on this subject and of course with a great experience in the field.

This book presents the actual state of the pancreatic tumor, specifically referred to as adeno‐ carcinoma of the pancreas because this is the more common primary malignant tumor and has achieved advances in diagnosis and treatment.

The incidence of pancreatic carcinoma has markedly increased over the past several decades and ranks as the fourth leading cause of cancer death all over the world. Despite the highmortality rate associated with pancreatic cancer, its etiology is poorly understood. Risk fac‐ tors for development of this kind of malignant tumor include a family history of pancreatic cancer, heavy cigarette smoking, obesity, chronic pancreatitis of long-standing evolution, and unknown factors.

Pancreatic cancer symptoms depend on the site of the tumor within the pancreas and the degree of tumor involvement. In the early stages of pancreatic cancer, there are not many noticeable symptoms. As the cancer grows, symptoms may include jaundice, light-colored stools or dark urine, pain in the upper or middle abdomen and back, weight loss for un‐ known reason, loss of appetite, and marked fatigue.

It is a tumor difficult to detect and diagnose for the following reasons. There are no noticea‐ ble signs or symptoms in the early stages of pancreatic cancer. The signs when present are like the other found in many other benign illnesses, such as chronic pancreatitis or peptic ulcer. The pancreas is obscured by other organs in the abdomen and is difficult to visualize clearly on imaging tests. To appropriately treat pancreatic cancer, it is crucial to evaluate whether the cancer can be resected.

The use of imaging technology may aid in the diagnosis of pancreatic cancer and in the identi‐ fication of patients with disease that is not amenable to resection. Imaging tests that may be used include helical computed tomographic (HCT) scan, magnetic resonance imaging (MRI) scan, and endoscopic ultrasound (USE). Minimally invasive techniques, such as laparoscopy and laparoscopic ultrasound, may be used to decrease the use of unnecessary laparotomy.

No tumor-specific markers exist for pancreatic cancer; markers such as serum cancer antigen (CA) 19-9 have a low specificity. Most patients with pancreatic cancer will have an elevated CA 19-9 at diagnosis. Following or during a definitive therapy, an increase in CA 19-9 levels may identify patients with progressive tumor growth. The presence of a normal CA 19-9, however, does not preclude recurrence.

Primary factors that influence prognosis are whether (a) the tumor is localized and can be completely resected and (b) the tumor has spread to lymph nodes or elsewhere. Exocrine pancreatic cancer is rarely curable and has an overall survival (OS) rate of less than 6%. The highest cure rate occurs when the tumor is truly localized to the pancreas; however, this stage of the disease accounts for less than 20% of cases. For patients with localized disease and small cancers (<2 cm) with no lymph node metastases and no extension beyond the cap‐ sule of the pancreas, complete surgical resection is associated with an actuarial 5-year sur‐ vival rate of 18–24%.

Surgical resection is the mainstay of curative treatment and provides a survival benefit in patients with small, localized pancreatic tumors. Patients with unresectable, metastatic, or recurrent disease are unlikely to benefit from surgical resection. Pancreatic tumors are resist‐ ant to treatment with chemotherapy and radiation. Patients with any stage of pancreatic cancer can appropriately be considered candidates for clinical trials because of the poor re‐ sponse to chemotherapy, radiation therapy, and surgery as conventionally used.

Palliation of symptoms may be achieved with conventional treatment. Palliative measures that may improve quality of life while not affecting OS include surgical or endoscopic or radiologic biliary decompression, relief of gastric outlet obstruction, pain control, and psy‐ chological care to address the potentially disabling psychological events associated with the diagnosis and treatment of pancreatic cancer.

Finally, I would like to thank all the authors for their excellent contributions and the Intech Editorial Team, especially Ms. Marijana Francetic for her continuous support and superb and constant help during the whole editorial process.

> **Prof. Luis Rodrigo, MD** Emeritus Full Professor of Medicine University of Oviedo Oviedo, Spain

**Section 1**

**Etiopathogenesis and Diagnosis**

**Etiopathogenesis and Diagnosis**

Primary factors that influence prognosis are whether (a) the tumor is localized and can be completely resected and (b) the tumor has spread to lymph nodes or elsewhere. Exocrine pancreatic cancer is rarely curable and has an overall survival (OS) rate of less than 6%. The highest cure rate occurs when the tumor is truly localized to the pancreas; however, this stage of the disease accounts for less than 20% of cases. For patients with localized disease and small cancers (<2 cm) with no lymph node metastases and no extension beyond the cap‐ sule of the pancreas, complete surgical resection is associated with an actuarial 5-year sur‐

Surgical resection is the mainstay of curative treatment and provides a survival benefit in patients with small, localized pancreatic tumors. Patients with unresectable, metastatic, or recurrent disease are unlikely to benefit from surgical resection. Pancreatic tumors are resist‐ ant to treatment with chemotherapy and radiation. Patients with any stage of pancreatic cancer can appropriately be considered candidates for clinical trials because of the poor re‐

Palliation of symptoms may be achieved with conventional treatment. Palliative measures that may improve quality of life while not affecting OS include surgical or endoscopic or radiologic biliary decompression, relief of gastric outlet obstruction, pain control, and psy‐ chological care to address the potentially disabling psychological events associated with the

Finally, I would like to thank all the authors for their excellent contributions and the Intech Editorial Team, especially Ms. Marijana Francetic for her continuous support and superb

**Prof. Luis Rodrigo, MD**

University of Oviedo Oviedo, Spain

Emeritus Full Professor of Medicine

sponse to chemotherapy, radiation therapy, and surgery as conventionally used.

vival rate of 18–24%.

VIII Preface

diagnosis and treatment of pancreatic cancer.

and constant help during the whole editorial process.

**Chapter 1**

**Provisional chapter**

**Systemic Inflammatory Response in Pancreatic Ductal**

**Systemic Inflammatory Response in Pancreatic Ductal** 

Pancreatic ductal adenocarcinoma induces systemic inflammatory response (SIR), which can be assessed either by ratios between blood cell counts (neutrophil to lymphocyte ratio, NLR; platelet to lymphocyte ratio, PLR) or concentrations of acute phase proteins, clotting factors and albumins. These tests are biologically justified by multiple events including bone marrow activation, development of immune-suppressing immature myeloid cells, generation of pre-metastatic niches and neutrophil extracellular trap formation from externalised DNA network in bidirectional association with platelet activation. Despite biological complexity, clinical assessment of SIR is widely available, patient-friendly and economically feasible. In this chapter, we present a review on NLR, PLR, Glasgow prognostic score and fibrinogen, recently reported to have a prognostic role regarding overall survival, cancer/progression free and cancer-specific survival in early and advanced pancreatic ductal adenocarcinoma. Practical consequences abound, including preference for surgical or combined, active or sparing treatment, as well as prediction of non-resectability or chemotherapy response. In this chapter, we also scrutinise the main controversies including different cut-off levels, hypothetic correlation with tumour burden and morphology, negative findings and discussions on the best marker. Future developments should include elaboration of complex scores as will be

**Keywords:** pancreatic ductal adenocarcinoma, systemic inflammatory response, neutrophil to lymphocyte ratio, NLR, platelet to lymphocyte ratio, PLR, Glasgow

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: 10.5772/intechopen.78954

**Adenocarcinoma**

**Adenocarcinoma**

Janis Gardovskis

Janis Gardovskis

**Abstract**

described here.

prognostic score, fibrinogen

Arturs Silovs, Ilze Strumfa, Reinis Riekstins,

Arturs Silovs, Ilze Strumfa, Reinis Riekstins,

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

Zane Simtniece, Andrejs Vanags and

Zane Simtniece, Andrejs Vanags and

http://dx.doi.org/10.5772/intechopen.78954

#### **Systemic Inflammatory Response in Pancreatic Ductal Adenocarcinoma Systemic Inflammatory Response in Pancreatic Ductal Adenocarcinoma**

DOI: 10.5772/intechopen.78954

Arturs Silovs, Ilze Strumfa, Reinis Riekstins, Zane Simtniece, Andrejs Vanags and Janis Gardovskis Arturs Silovs, Ilze Strumfa, Reinis Riekstins, Zane Simtniece, Andrejs Vanags and Janis Gardovskis

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.78954

#### **Abstract**

Pancreatic ductal adenocarcinoma induces systemic inflammatory response (SIR), which can be assessed either by ratios between blood cell counts (neutrophil to lymphocyte ratio, NLR; platelet to lymphocyte ratio, PLR) or concentrations of acute phase proteins, clotting factors and albumins. These tests are biologically justified by multiple events including bone marrow activation, development of immune-suppressing immature myeloid cells, generation of pre-metastatic niches and neutrophil extracellular trap formation from externalised DNA network in bidirectional association with platelet activation. Despite biological complexity, clinical assessment of SIR is widely available, patient-friendly and economically feasible. In this chapter, we present a review on NLR, PLR, Glasgow prognostic score and fibrinogen, recently reported to have a prognostic role regarding overall survival, cancer/progression free and cancer-specific survival in early and advanced pancreatic ductal adenocarcinoma. Practical consequences abound, including preference for surgical or combined, active or sparing treatment, as well as prediction of non-resectability or chemotherapy response. In this chapter, we also scrutinise the main controversies including different cut-off levels, hypothetic correlation with tumour burden and morphology, negative findings and discussions on the best marker. Future developments should include elaboration of complex scores as will be described here.

**Keywords:** pancreatic ductal adenocarcinoma, systemic inflammatory response, neutrophil to lymphocyte ratio, NLR, platelet to lymphocyte ratio, PLR, Glasgow prognostic score, fibrinogen

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
