Pancreatic cancer incidence has been increasing in recent years, probably due to improved diagnostic techniques (CT abdomen, abdominal MRI, and endoscopic ultrasound with fine-needle aspiration).

STAFF

At the IEO pancreatic cancer is treated by a multidisciplinary team consisting of specialists in:

• Abdomino - pelvic surgery
• Gastrointestinal and Neuroendocrine Cancer Medical Treatment
• Endoscopy
• New Drugs and Early Drug Development for Innovative Therapies
• Department of Pathology and Laboratory Medicine
• Department of Medical Imaging and Radiation Sciences

There is no specific screening for pancreatic cancer that may allow early diagnosis. The cause of pancreatic cancer is unknown. Some pancreatic cancer risk factors are cigarette smoking, a diet rich in meat and low in fruit and vegetables, obesity, alcohol abuse, diabetes mellitus, and chronic pancreatitis. In very rare cases, there is a hereditary predisposition of pancreatic cancer as a possible factor in the development of it (about 3%). The term familial pancreatic cancer (FPC) is used in the context of families with at least two first-degree relatives with pancreatic cancer.

Although the genetic defect responsible for the majority of cases of familial pancreatic cancer has not yet been recognised, the list of syndromes with specific genetic alterations at greater risk of developing pancreatic cancer is increasing. These syndromes include Familial Atypical Multiple Mole Melanoma (FAMMM), Peutz-Jeghers Syndrome (PJS), Hereditary Pancreatitis (HP), Hereditary Nonpolyposis Colorectal Cancer (HNPCC), syndrome of Hereditary Breast and Ovarian Cancer (HBOC), Cystic Fibrosis (CF), Familial Adenomatous Polyposis (FAP), Ataxia-Telangiectasia (AT), and Fanconi’s Anaemia (FA).

At the IEO, study and research programs focused on this specific pancreatic cancer have been active for years.

Nutritional prevention

Based on a careful evaluation of the results of scientific research, it has been possible to identify specific risk factors and protective nutritional factors for specific types of pancreatic cancer. Experts have classified the results into four levels: "convincing evidence", "probable evidence", "limited evidence" and one last level that collects the effects for which evidence of association with the tumour is "highly unlikely."

Risk factors for pancreatic cancer

• Overweight and obesity (convincing evidence)
• Abdominal fat (probable evidence)

Protective factors for pancreatic cancer

Folate-rich foods such as green leafy vegetables (spinach, endive, escarole, chard), broccoli, wheat germ (probable evidence).

Symptoms of pancreatic cancer

Pancreatic cancer symptoms are not easily recognised and related to the cancer; they often occur too late when the pancreatic cancer has reached an advanced stage and therefore not able to undergo surgical resection. The most common pancreatic cancer symptoms include: jaundice (yellowing of the skin), weight loss, decreased appetite, digestive disorders, and abdominal pain often radiating to the back.

As pancreatic cancer progresses, it can cause:

• Weight loss. A number of factors may cause weight loss in people with pancreatic cancer. Symptoms of pancreatic cancer itself may cause weight loss. Nausea and vomiting caused by cancer treatments or a pancreatic cancer pressing on your stomach may make it difficult to eat. Your body may have difficulty processing nutrients from food because your pancreas is failing to make enough digestive juices.
• Jaundice. Pancreatic cancer that blocks the liver's bile duct can cause jaundice. Symptoms of pancreatic cancer include yellow skin and eyes, dark-colored urine, and pale-colored stools. Jaundice usually occurs without abdominal pain.
• Pain. A growing pancreatic cancer may press on nerves in your abdomen, causing pain that can become severe. Pain medications can help you feel more comfortable.
• Bowel obstruction. Pancreatic cancer that grows into or presses on the first part of the small intestine (duodenum) can block the flow of digested food from your stomach into your intestines.

Surgery is still the cornerstone in the treatment of pancreatic cancer. Unfortunately, only 5% to 20% of all pancreatic cancers can be resected radically on diagnosis. The type of surgery depends on the affected location in the pancreas, the size of the pancreatic cancer, and the need to obtain resection margins free of disease. Therefore, while in some cases the preservation of the pancreas is possible (duodenum-cephalo-pancreatectomy, distal splenic-pancreatectomy), in other cases the pancreatic gland must be completely removed (total pancreatectomy) with resulting pancreatic insufficiency, and diabetes mellitus.

For a possible resection surgery of pancreatic cancer, it is fundamental to contact centres of reference, where perioperative morbidity and mortality are reduced to a minimum. This depends on the one hand on expertise and experience arising from operating on a high number of pancreatic cancer cases; and on the other, the expertise of different professionals working in harmony with one another (surgical oncologist, medical oncologist, radiologist, gastroenterologist, endoscopist, interventional radiologist, pathologist, nutritionist, endocrinologist). All these professionals have been at the IEO since its foundation and they collaborate actively in the optimisation of diagnosis and treatment patterns of pancreatic cancer.

Advances in technology, techniques, and minimally-invasive surgical instruments have encouraged the application of the minimally-invasive laparoscopic approach to the treatment of pancreatic cancer. Procedures such as laparoscopic staging and remote pancreatectomy have proven feasible and safe and appear to offer significant advantages compared to their corresponding surgeries performed by laparotomic access.

The effects on nutritional status and overall patient health due to the absence of the pancreas, as a consequence of pancreatic cancer resection, are effectively prevented through recommendations and personalised diet plans, provided by specialised personnel at the time of hospital discharge and during successive follow-ups. Possible metabolism alterations, due to pancreatic cancer, including diabetes mellitus, are properly evaluated and promptly corrected with the support of endocrinologists. Both types of specialist are present at the IEO and are an important resource for the overall management of the patient affected by pancreatic cancer.

Adjuvant chemotherapy, aimed at preventing pancreatic cancer recurrence, represents a reasonable approach in patients who are considered at high risk of relapse, although undergoing curative resection. In locally-advanced, unresectable or metastatic pancreatic cancer, chemotherapy alone is the treatment of reference. In recent years, systematic research has been made possible by optimising the treatment of advanced forms of pancreatic cancer with improved survival and patients' quality of life, mainly due to new combinations of the chemotherapy drugs.
For patients with jaundice, the placement of an internal biliary prosthesis by endoscopic route (by endoscopic retrograde cholangio-pancreatography, ERCP), is a viable alternative to palliative surgery with success rates up to 85%, low risk of mortality (1-2%) and significant reduction in the duration of hospitalisation for patients affected by pancreatic cancer.
In gastro-resected patients or patients that for other reasons cannot undergo internal prosthetic, external biliary drainage placement could be considered.

Clinical trials currently underway at IEO for this type of pancreatic cancer are investigating addressing the application of new biological drugs in the treatment of metastatic pancreatic cancer and neoadjuvant chemotherapy in potentially resectable disease. Finally, one area of absolute novelty is the search for molecular markers both in sporadic and family-hereditary forms of pancreatic cancer.

Treatment of pancreatic cancer metastases

Pancreatic cancer is one of the most fatal malignancies with increased morbidity and mortality, and there has been no major treatment breakthrough. The 5-year survival rate of pancreatic cancer is only about 6%. The main reason for this low survival rate is because a large majority of the patients present with unresectable metastases. Liver metastases from pancreatic cancer are the most common, and even after curative surgery for resectable disease, more than 62% of patients will develop multiple liver metastases.
Life expectancy of patients affected by pancreatic cancer with liver metastases is low.
Palliative care has played an important role for patients with liver metastasis.
Systemic chemotherapy is now regarded as the main treatment approach for pancreatic cancer liver metastases; in addition, non-surgical liver-directed therapies, including radio frequency ablation, cryosurgery, and transarterial chemoembolization, are considered alternative therapeutic approaches for unresectable liver metastases. However, the optimal selection of treatment modalities for pancreatic cancer patients requires multidisciplinary coordination.

Pancreatic cancer can even lead to nutritional consequences, such as malnutrition, cachexia syndrome (characterized by loss of fat and lean mass), significant body weight loss and reduced food intake due to anorexia.

Nutritional consequences of pancreatic cancer resection

Nutritional consequences of pancreatic cancer resection also derive from the type of operation performed. For example, in the case of distal pancreatectomy, better digestive function and absorption are compared to duodeno-pancreatectomy. Interventions can lead to maldigestion and malabsorption (due to lack of pancreatic enzymes), especially of lipids and fat-soluble vitamins, resulting in steatorrhea (presence of undigested fats in the stool) and reduced body weight. Reduced absorption of protein and total energy can be experienced. Another very common complication is insulin-dependent diabetes.

During surgery, a small probe is generally positioned (nutritional jejunostomy) to ensure physiological nutrition in the postoperative period (through the use of Enteral Nutrition - EN) as well as the required amount of nourishment when intake through the mouth is poor or inadequate as compared to the need. The nutritional jejunostomy is left in place at the time of discharge, and is used in cases where the patient is unable to take a proper diet to cover the nutritional requirements. After pancreatic resection, fat content in the diet should be controlled (no more than 30% of total caloric intake).

Depending on the surgery performed, taking capsules of pancreatic enzymes may be required. In specific cases the introduction of MCT to the diet may be appropriate (medium chain triglycerides). They are more easily digested and more quickly metabolised fats. The amount of simple sugars (honey, syrups, fruit juices) in the diet should be also controlled (kept below 10% of the total caloric content).