Surg Oncol Clin N Am

Genetics of pancreatic cancer. From genes to families.

Hruban RH. Petersen GM. Ha PK. Kern SE.
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Cancer of the pancreas is a genetic disease. Sporadic cancers of the pancreas are frequently associated with the activation of an oncogene, K-ras, and the inactivation of multiple tumor suppressor genes, including p53, DPC4, p16, and BRCA2. An improved understanding of the genetics of pancreas cancer should lead to new tests to screen for this disease and novel rational gene-based therapies.

Role of growth factors in pancreatic cancer.

Korc M.
Department of Medicine, University of California at Irvine, Irvine, California 92697, USA.
Human pancreatic cancers overexpress a number of important tyrosine growth factor receptors and their ligands. These include the epidermal growth factor (EGF) receptor (EGFR) and related receptors, multiple ligands that bind to EGFR, certain fibroblast growth factors (FGF) receptors (FGFR) and ligands, and insulin-like growth factor I (IGF-I) and its receptor. The excessive activation of mitogenic signaling cascades that are modulated by these overexpressed ligands and receptors is compounded by the presence of mutations in the K-ras oncogene. Pancreatic cancers also overexpress transforming growth factor betas (TGF-betas) that usually inhibit the growth of epithelial cells. Pancreatic cancers, however, underexpress the type I TGF-beta receptor and harbor mutations in the smad4 gene, alterations that prevent TGF-betas from inhibiting cancer cell growth but that do not confer onto pancreatic actions that promote cancer growth in vivo. Together, these perturbations confer onto pancreatic cancer cells a tremendous growth advantage.

Pathology of cancer of the pancreas.

Wilentz RE. Hruban RH.
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Although many have lumped nearly 20 different neoplasms under the umbrella term "cancer of the pancreas," each of these neoplasms is pathologically and clinically distinct. In addition, each may require a specific treatment and result in a different outcome. Understanding the pathology of pancreas cancer, therefore, forms the cornerstone for rational treatment and prognostication. This article describes the pathology of a number of primary, metastatic, and systemic cancers that can involve the pancreas. The clinical relevance of each gross and histologic tumor feature is emphasized.

Epidemiology of and risk factors for pancreatic cancer.

Gold EB. Goldin SB.
Department of Epidemiology and Preventive Medicine, School of Medicine, University of California, Davis, California 95616, USA.
In the United States, incidence of and mortality from pancreatic cancer increased for several decades earlier in this century but have tended to level off in recent years. Rates increase with age and are higher in blacks than in whites and higher in men than in women. Cigarette smoking increases the risk of pancreatic cancer, while alcohol consumption largely shows no relationship, coffee consumption shows little, if any, association, and a number of occupational exposures seem to be associated but the results are not fully consistent. Finally, human studies have suggested positive associations with meat consumption and carbohydrate intake and a protective effect of dietary fiber and consumption of fruits and vegetables. Thus, much progress has been made in the last two decades in identifying risk factors, but much epidemiologic work is needed to identify and reduce putative exposures.

CA 19-9 in pancreatic cancer.

Ritts RE. Pitt HA.
Mayo Medical School, Mayo Clinic Foundation, Rochester, Minnesota, USA.
CA 19-9 has achieved a defined role in the diagnosis, prognosis, and monitoring of patients with pancreatic cancer. For diagnosis, a reference value above 200 u/mL in a nonjaundiced patient with a confirming CT scan has a very high predictive value. For prognosis, a low preoperative value and a normal value after resection predict a good outcome. Similarly, CA 19-9 levels have been used successfully in monitoring the response to neoadjuvant therapy.

CT and MR evaluation of pancreatic cancer.

Bluemke DA. Fishman EK.
Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
CT scanning has a greater than 90% accuracy in staging patients with pancreatic cancer. New, powerful imaging techniques, such as spiral CT and gadolinium-enhanced MRI, can evaluate subtle changes in pancreatic contours and overall vascularity of the gland to further increase staging reliability. Spiral CT in particular provides excellent depiction of small vessels, high levels of pancreatic enhancement, and lack of respiratory misregistration. High resolution contrast-enhanced MR techniques may provide a new role for MR imaging in the evaluation of pancreatic cancer. This article discusses state-of-the-art CT and MR imaging techniques for pancreatic evaluation.

The role of endosonography in the diagnosis and management of pancreatic cancer.

Stevens PD. Lightdale CJ.
Columbia-Presbyterian Medical Center, New York, New York 10032, USA.
Among the various diagnostic tests that may be used to detect and stage pancreatic cancer, endoscopic ultrasound (EUS) is among the most promising. It is a highly sensitive test for detecting pancreatic tumors and for detecting the invasion of these tumors into the portal venous system or loco-regional lymph nodes. With the development of EUS-guided fine-needle puncture, tissue diagnosis of imaged lesions is now possible. This latest advance has improved the specificity and overall accuracy of EUS and also allows for the development of therapeutic applications, such as celiac plexus neurolysis. In this article we review the materials, methods, and clinical applications of EUS for the evaluation of pancreatic cancer.

Pylorus-preserving pancreaticoduodenectomy.

Yeo CJ.
Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4606, USA.
In patients with resectable adenocarcinoma of the head of the pancreas, pancreaticoduodenectomy serves as the cancer-directed operation of choice. The pylorus-preserving modification of pancreaticoduodenectomy is commonly performed in this setting. Reconstruction of the gastrointestinal tract following pylorus-preserving pancreaticoduodenectomy can be accomplished using various techniques. The operative mortality rate in experienced hands is generally less than 3%, with a postoperative complication rate in the range of 35% to 40%. Patient survival following resection is largely determined by tumor biology, based on such parameters as tumor diameter, lymph node status, resection margin status, and DNA content, and is not adversely influenced by pylorus-preserving pancreaticoduodenectomy.

Radical pancreatectomy.

Reber HA. Gloor B.
Section of Gastrointestinal Surgery, University of California-Los Angeles, Los Angeles, California 90095-6904, USA.
In an effort to cure more patients, the standard pancreaticoduodenectomy (Whipple procedure) has been modified to include a wider soft tissue and lymph node dissection, and a resection of a segment of the superior mesenteric and portal veins. The operation is described, and the results are critically reviewed. Although the procedure can be performed safely, and with little additional morbidity compared to a standard resection, there is no objective evidence that it increases the cure rate.

Portal vein resection for pancreatic adenocarcinoma.

Harrison LE. Brennan MF.
Department of Surgery, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA.
Although isolated portal vein involvement has classically been a contraindication for resection, portal vein resection can be performed safely with a low perioperative mortality rate. Importantly, overall survival is similar between patients undergoing pancreatectomy with portal vein resection and those undergoing standard pancreatic resection. Suspected isolated portal vein involvement, therefore, frequently does not preclude operability and, by itself, should not be a contraindication for pancreatic resection.

Neoadjuvant chemoradiation for adenocarcinoma of the pancreas.

Miller AR. Robinson EK. Lee JE. Pisters PW. Chiao PJ. Lenzi RL. Abbruzzese JL. Evans DB.
Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Pancreaticoduodenectomy is performed on carefully selected patients as part of a protocol-based clinical research program emphasizing the importance of multimodality management for patients with potentially resectable adenocarcinoma of the pancreatic head. Treatment schemas emphasize the importance of minimizing toxicity and treatment duration, while attempting to improve therapeutic efficacy. Cytotoxicity is enhanced by combining radiation therapy with more potent radiation-sensitizing agents. Because of the high incidence of liver metastases, systemic therapy is continued after chemoradiation and surgery with systemic agents of low toxicity directed at specific molecular events involved in pancreatic tumorigenesis such as inhibition of angiogenesis, induction of apoptosis, or arrest of the cell cycle.

Palliative therapy for pancreatic cancer.

Lillemoe KD.
Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4679, USA.
The majority of patients with pancreatic cancer are not resectable for cure at the time of presentation. Therefore, palliation of symptoms-obstructive jaundice, duodenal obstruction, and pain-are of primary importance. Obstructive jaundice is the most common presenting symptom for cancer of the pancreas and can be managed by surgical and nonoperative techniques. The decision to perform nonoperative versus surgical palliation for pancreatic cancer is influenced by the patient's symptoms, overall health status, projected survival, and the expected procedure-related morbidity and mortality. The major advantage for surgical palliation is the ability of a single procedure to combine adequate long-term palliation for all three primary symptoms of the disease. Most surgical series report acceptable hospital morbidity, mortality, and a reasonable postoperative length of stay.

Gene therapy and pancreatic cancer.

Clary BM. Lyerly HK.
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
In the short time since the inception of gene therapy, significant advances have been realized. Although this progress has not realized definitive breakthroughs in the treatment of solid organ tumors, including pancreatic cancer, the hope is that advances will come with improved gene delivery systems and alternative approaches. The authors review the history of gene therapy, the current treatment strategies and delivery systems, the preclinical studies on its application to pancreatic cancer, and provide an up-to-date list of federally approved gene therapy cancer trials.

Pylorus-preserving pancreaticoduodenectomy.

Yeo CJ.
Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4606, USA.
In patients with resectable adenocarcinoma of the head of the pancreas, pancreaticoduodenectomy serves as the cancer-directed operation of choice. The pylorus-preserving modification of pancreaticoduodenectomy is commonly performed in this setting. Reconstruction of the gastrointestinal tract following pylorus-preserving pancreaticoduodenectomy can be accomplished using various techniques. The operative mortality rate in experienced hands is generally less than 3%, with a postoperative complication rate in the range of 35% to 40%. Patient survival following resection is largely determined by tumor biology, based on such parameters as tumor diameter, lymph node status, resection margin status, and DNA content, and is not adversely influenced by pylorus-preserving pancreaticoduodenectomy.

Radical pancreatectomy.

Reber HA. Gloor B.
Section of Gastrointestinal Surgery, University of California-Los Angeles, Los Angeles, California 90095-6904, USA.
In an effort to cure more patients, the standard pancreaticoduodenectomy (Whipple procedure) has been modified to include a wider soft tissue and lymph node dissection, and a resection of a segment of the superior mesenteric and portal veins. The operation is described, and the results are critically reviewed. Although the procedure can be performed safely, and with little additional morbidity compared to a standard resection, there is no objective evidence that it increases the cure rate.

Portal vein resection for pancreatic adenocarcinoma.

Harrison LE. Brennan MF.
Department of Surgery, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA.
Although isolated portal vein involvement has classically been a contraindication for resection, portal vein resection can be performed safely with a low perioperative mortality rate. Importantly, overall survival is similar between patients undergoing pancreatectomy with portal vein resection and those undergoing standard pancreatic resection. Suspected isolated portal vein involvement, therefore, frequently does not preclude operability and, by itself, should not be a contraindication for pancreatic resection.

Neoadjuvant chemoradiation for adenocarcinoma of the pancreas.

Miller AR. Robinson EK. Lee JE. Pisters PW. Chiao PJ. Lenzi RL. Abbruzzese JL. Evans DB.
Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Pancreaticoduodenectomy is performed on carefully selected patients as part of a protocol-based clinical research program emphasizing the importance of multimodality management for patients with potentially resectable adenocarcinoma of the pancreatic head. Treatment schemas emphasize the importance of minimizing toxicity and treatment duration, while attempting to improve therapeutic efficacy. Cytotoxicity is enhanced by combining radiation therapy with more potent radiation-sensitizing agents. Because of the high incidence of liver metastases, systemic therapy is continued after chemoradiation and surgery with systemic agents of low toxicity directed at specific molecular events involved in pancreatic tumorigenesis such as inhibition of angiogenesis, induction of apoptosis, or arrest of the cell cycle.

Palliative therapy for pancreatic cancer.

Lillemoe KD.
Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4679, USA.
The majority of patients with pancreatic cancer are not resectable for cure at the time of presentation. Therefore, palliation of symptoms-obstructive jaundice, duodenal obstruction, and pain-are of primary importance. Obstructive jaundice is the most common presenting symptom for cancer of the pancreas and can be managed by surgical and nonoperative techniques. The decision to perform nonoperative versus surgical palliation for pancreatic cancer is influenced by the patient's symptoms, overall health status, projected survival, and the expected procedure-related morbidity and mortality. The major advantage for surgical palliation is the ability of a single procedure to combine adequate long-term palliation for all three primary symptoms of the disease. Most surgical series report acceptable hospital morbidity, mortality, and a reasonable postoperative length of stay.

Gene therapy and pancreatic cancer.

Clary BM. Lyerly HK.
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
In the short time since the inception of gene therapy, significant advances have been realized. Although this progress has not realized definitive breakthroughs in the treatment of solid organ tumors, including pancreatic cancer, the hope is that advances will come with improved gene delivery systems and alternative approaches. The authors review the history of gene therapy, the current treatment strategies and delivery systems, the preclinical studies on its application to pancreatic cancer, and provide an up-to-date list of federally approved gene therapy cancer trials.

Cancer in pregnancy.

Year 1998
Falkenberry SS.
Department of Obstetrics and Gynecology, Brown University, Women and Infants' Hospital, Providence, Rhode Island, USA.
Cancer in pregnancy requires the careful consideration of multiple complex issues to achieve the most favorable outcome for mother and fetus. Presented are the principles of surgery, radiation, and chemotherapy as they pertain to pregnancy, and a discussion of site-specific cancers.

Gene therapy for liver tumors.

Year 1998
Carroll NM. Tanabe KK.
Division of Surgical Oncology, Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
The liver is a common site of metastases from solid tumors and the primary site for a number of malignancies. Cure rates for primary and metastatic liver tumors are low. Gene therapy is a novel approach to liver cancer that seeks to exploit differences between tumor cells and hepatocytes to achieve tumor eradication with preservation of normal hepatic parenchyma. Numerous strategies for tumor specific cytolysis are reviewed.