Pancreas Tumors

Endoscopic ultrasound (EUS), or echoendoscopy, is an advanced diagnostic technique that enables high-resolution ultrasonographic imaging of the esophageal, gastric, and duodenal walls, with a spatial resolution of approximately 1–2 mm. It also allows highly accurate evaluation of adjacent organs and structures, including the pancreas, biliary tree, mediastinum, vascular structures, and regional lymph nodes.

The procedure is performed using an echoendoscope, an instrument similar to a conventional endoscope, but equipped with a distal ultrasound transducer in addition to the optical camera. This dual capability permits detailed assessment of both the gastrointestinal wall layers and surrounding anatomical structures.

EUS is considered a second-level diagnostic modality, providing detailed information that may not be obtainable with other non-invasive imaging techniques.

Examination of the upper gastrointestinal tract with EUS is comparable to standard gastroscopy, although it typically requires a longer duration depending on the clinical indication and whether interventional procedures are performed. For this reason, the examination is usually carried out under sedation with anesthesiological support. In selected cases requiring more complex interventions, general anesthesia with endotracheal intubation may be indicated.

The echoendoscope is introduced orally and advanced under direct visualization through the esophagus and stomach into the duodenum.

For evaluation of the upper digestive tract (esophagus, stomach, duodenum, biliary system, pancreas, and mediastinum), patients are required to fast for at least 8 hours for solid food and 2 hours for clear liquids.

During EUS, interventional procedures such as fine-needle aspiration or biopsy (EUS-FNA/FNB) may be performed. These techniques involve obtaining tissue or cellular samples using dedicated needles introduced under real-time ultrasound guidance into the target lesion. The collected specimens are subsequently submitted for cytological or histological analysis.

Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive endoscopic procedure performed within the Division of Gastroenterology and Digestive Endoscopy. It is used for both the diagnosis and treatment of conditions that impair the flow of bile and pancreatic secretions into the intestine.

The procedure is carried out under general anesthesia in an inpatient setting. Patient positioning (prone, supine, or left lateral decubitus) is determined by procedural requirements. A duodenoscope—a flexible endoscope equipped with a light source and a side-viewing camera—is introduced orally and advanced to the second portion of the duodenum, where the major duodenal papilla (papilla of Vater) is located, representing the outlet of the biliary and pancreatic ducts.

Through the working channel of the duodenoscope, dedicated accessories are introduced for diagnostic and therapeutic purposes. Selective cannulation of the papilla is performed using a catheter, followed by injection of radiopaque contrast medium into the biliary and/or pancreatic ducts. Fluoroscopic imaging allows visualization of the ductal system, facilitating diagnostic assessment and therapeutic planning.

It then advances to the therapeutic phase, most commonly involving sphincterotomy, an incision of the papillary sphincter that allows access to the ductal system and facilitates subsequent interventions. The examination lasts approximately 60 minutes, and patients must fast for at least 12 hours beforehand.

Due to the use of ionizing radiation, all women of childbearing potential must be assessed for pregnancy. In cases of uncertainty, a pregnancy test is performed before the procedure.

During ERCP, additional interventions may include:

• Biopsy: collection of tissue samples for histological analysis
• Biliary or pancreatic sphincterotomy: incision of the sphincter at the level of the papilla of Vater to access the upstream ducts
• Stent placement: insertion of plastic or metal stents to relieve strictures or obstructions of the biliary or pancreatic ducts. In malignant stenosis, stenting may be performed preoperatively to resolve jaundice or as palliative treatment in unresectable disease

ERCP is a technically demanding procedure associated with potential complications, including acute pancreatitis (approximately 3.5%), bleeding (1.3%), perforation (0.1–0.6%), and infection (1–2%).

For the diagnosis and staging of pancreatic cancer, ERCP may be complemented by the following imaging studies:

• Contrast-enhanced computed tomography (CT) of the chest and abdomen
• Magnetic resonance cholangiopancreatography (MRCP)

Through a blood test, it is possible to measure the levels of two proteins known as tumor markers, specifically carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), which may be produced by pancreatic cancer cells.

Serum concentrations of these markers may correlate with tumor burden and often increase as the disease progresses. When elevated, they can support the assessment of disease extent, as well as help monitor its course over time and evaluate response to treatment.

The diagnosis of pancreatic cancer is confirmed by histological examination performed by the pathologist on tissue samples obtained during endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP).

In the evaluation of tumor specimens, the pathologist assesses the overall tissue architecture and defines the histological subtype. This classification is of key biological and clinical relevance, as it provides essential information for therapeutic planning and prognosis.

The main types of pancreatic tumors include:

• Adenocarcinoma: the most common histological type of pancreatic cancer, accounting for the vast majority of cases.
• Neuroendocrine tumors/carcinomas: a less frequent group of neoplasms characterized by distinct biological behavior and therapeutic approaches compared with adenocarcinoma.
• Cystic tumors: a heterogeneous group that includes mucinous and serous cystic neoplasms.
• IPMN (intraductal papillary mucinous neoplasm): a precursor lesion characterized by intraductal growth and mucin production, with variable malignant potential.

Surgery is indicated when the tumor is confined to the pancreas. In patients with adenocarcinoma, this situation is present in approximately 25% of cases, while it is more frequently observed in other histological subtypes.
The type of surgical procedure depends on the location of the lesion:

• Pancreaticoduodenectomy (Whipple procedure): indicated for tumors of the pancreatic head. It involves en bloc resection of the pancreatic head, duodenum, distal stomach, gallbladder, and extrahepatic bile ducts.
• Distal pancreatectomy: indicated for tumors of the body or tail of the pancreas, which are removed en bloc, often together with the spleen.
• Total pancreatectomy: entails removal of the entire pancreas, together with portions of the small intestine and stomach, the bile duct, gallbladder, spleen, and regional lymph nodes.

These procedures may be performed via open surgery or, in selected cases, using minimally invasive approaches such as laparoscopy or robotic-assisted surgery.
In all cases, these are complex operations involving both resection and reconstruction phases and are associated with a significant risk of postoperative complications. For this reason, they should be performed in specialized high-volume centers with appropriate expertise.
When the disease has spread to distant sites and is deemed unresectable, surgery may still have a palliative role, with procedures aimed at relieving symptoms, such as biliary or gastric bypass.

In recent years, the ERAS (Enhanced Recovery After Surgery) protocol has become increasingly established. This multimodal perioperative care pathway is designed to enhance and accelerate postoperative recovery by reducing surgical stress and supporting early functional rehabilitation.

It comprises a coordinated set of evidence-based measures, including comprehensive preoperative counselling, structured prehabilitation, selective or limited use of bowel preparation and nasogastric tubes, early removal of urinary catheters, and a reduced reliance on systemic opioid analgesia. Analgesic strategies may include epidural anesthesia, which provides targeted pain control at the spinal level while minimizing systemic opioid-related side effects. Additional key components include the use of prokinetic agents to promote gastrointestinal motility, early mobilization, and prompt reintroduction of oral fluids and nutrition.

Collectively, these interventions facilitate a faster return to baseline physiological function, shorten hospital stay, and reduce the incidence of postoperative complications, including hospital-acquired infections and thromboembolic events.

At discharge, a follow-up visit is scheduled. During this appointment, the final histological results are communicated to the patient, and an individualized oncological surveillance plan is established for ongoing monitoring.

Chemotherapy involves the use of cytotoxic drugs designed to inhibit cancer cell growth and proliferation, ultimately leading to cell death. A defining feature of malignant cells is their rapid and uncontrolled division, which also makes them particularly susceptible to these agents. However, certain healthy tissues with high cellular turnover may likewise be affected, leading to treatment-related adverse effects, commonly referred to as “side effects,” described below.

Chemotherapy is administered in cycles with varying schedules (daily, weekly, or every three weeks). The overall duration and frequency depend on the specific drugs used; in most cases, treatment is delivered on an outpatient basis without the need for hospital admission.

In selected patients, chemotherapy or chemoradiotherapy may be administered before and/or after surgery as part of a perioperative treatment strategy, even in potentially resectable disease. Eligibility depends on tumor stage and individual risk factors. Perioperative therapy is classified as:

• Adjuvant therapy: administered after surgery to reduce the risk of recurrence by targeting potential microscopic residual disease not visible to the naked eye.
• Neoadjuvant therapy: administered before surgery to facilitate resection, potentially reducing tumor size and the risk of local recurrence, particularly in the presence of regional lymph node involvement.

In advanced disease, systemic chemotherapy represents the standard treatment and is primarily aimed at controlling tumor progression and transforming the disease into a chronic condition.

Commonly used chemotherapeutic agents in pancreatic cancer include:

• 5-Fluorouracil (5-FU) in combination with folinic acid (intravenous administration)
• Gemcitabine (intravenous administration)
• Irinotecan (intravenous administration)
• Cisplatin (intravenous administration)
• Oxaliplatin (intravenous administration)
• Nab-paclitaxel (intravenous administration)
• Capecitabine (oral administration)

These agents may be used in combination regimens, sequentially, or as single therapies depending on the clinical context. Treatment selection is individualized by the oncologist based on tumor characteristics, stage of disease, the patient’s general condition, and previous treatments.

In addition, numerous clinical trials are ongoing to identify more effective strategies for advanced disease, including optimized drug combinations and dosing schedules. Novel agents with different mechanisms of action—often designed to increase selectivity for cancer cells and potentially reduce toxicity—are also under investigation. In selected cases, participation in clinical trials may be proposed.

Side effects of chemotherapy

Adverse effects vary between individuals and are generally reversible. The most common include nausea and vomiting, cutaneous reactions, anemia, leukopenia and thrombocytopenia, fatigue, and alopecia.

A broad range of supportive therapies is now available to prevent and manage many of these toxicities effectively. Nevertheless, treatment tolerance is highly individual, and chemotherapy regimens may be adjusted in terms of dose or schedule according to patient-specific factors.

Radiotherapy is a localized, non-invasive treatment that uses high-energy ionizing radiation to damage DNA and induce cell death in neoplastic tissues within the targeted area.

It is typically delivered on an outpatient basis, with sessions administered Monday to Friday, excluding weekends and public holidays. Each session lasts approximately 10–20 minutes, while the overall treatment course varies according to technique and disease stage, generally ranging from one to six weeks. Radiotherapy does not render patients radioactive, and they may safely maintain normal contact with others throughout the treatment period.

In pancreatic cancer, radiotherapy may be used alone or in combination with chemotherapy, depending on disease stage and clinical presentation. It can be delivered using conventional techniques or advanced stereotactic radiotherapy, which enables highly precise delivery of high doses per fraction over a limited number of sessions.

Treatment may be administered in the neoadjuvant setting, postoperatively, or in cases of residual or persistent disease following surgery. It may also be used with palliative intent to alleviate symptoms and reduce tumor burden in patients experiencing pain, jaundice, or other complications related to local tumor infiltration.

The most common side effects include nausea, gastrointestinal disturbances, and fatigue (asthenia).

The cancer patient is often a vulnerable individual who requires continuous support throughout the disease course. When new symptoms arise, whether related to the underlying disease or to treatment-related adverse effects, it is essential that timely specialist evaluation is ensured through a dedicated “fast track” pathway.

The Candiolo Cancer Institute provides a dedicated support service, available Monday to Friday from 8:00 a.m. to 5:00 p.m.

Patients may contact the Oncology Day Hospital Secretariat at +39 011.993.3775 to report the need for an urgent clinical assessment. The referring specialist is then promptly informed and will contact the patient to ensure timely evaluation and appropriate management.

At the Candiolo Cancer Institute, multidisciplinary specialists are available to provide patients, when needed or upon request, with comprehensive supportive care, including:

• Nutritional support
• Psychological support
• Physiotherapy
  Management
• Dressing of venous access devices
• Pain therapy
• Management of coexisting medical conditions

The Social Service Department of the Candiolo Cancer Institute conducts information and orientation interviews for patients and their families on how to access services in the area and how to obtain welfare and social security benefits provided by law (disability, benefits for aids and prostheses, work leave, etc.).

The service operates on Wednesdays and Fridays from 9 a.m. to 1 p.m. – Phone: +39 011.993.30

At the end of the treatment course, the follow-up phase begins. During this period, clinical evaluations and diagnostic tests are performed to monitor treatment-related side effects, assess therapeutic efficacy, and evaluate the patient’s functional recovery.

Follow-up is essential for the early detection of disease recurrence, enabling timely initiation of appropriate therapeutic strategies. It also provides an important opportunity for ongoing communication between the patient and the treating specialist.

Follow-up visits are scheduled by the same specialist physician, who assesses the patient’s clinical status and reviews the results of the required investigations.

Surveillance is typically conducted at predefined intervals over a period of 5–10 years and may include clinical examination, blood tests, tumor markers (CEA and CA 19-9), and contrast-enhanced computed tomography (CT) scans of the chest and abdomen.

Initially, follow-up is more frequent, generally every three to six months, and is then progressively spaced out over time, eventually transitioning to annual assessments. The frequency and type of investigations are individualized according to tumor stage and treatments received.

Due to the high volume of cases treated each year, the Candiolo Cancer Institute is a national reference center for the management of pancreatic cancer. Our experience enables us to address even the most complex clinical situations, consistently adopting a personalized approach tailored to the clinical and individual profile of each patient.

The definition of the treatment plan always begins with an accurate and timely diagnosis. Patients have access to state-of-the-art imaging technologies that enable precise assessment of disease extent.
In addition, the Institute provides advanced laboratory investigations, including molecular and genomic analyses, which are essential for identifying the biological characteristics of the tumor and guiding therapeutic decision-making.

When indicated, surgery is performed with minimally invasive techniques (laparoscopic or thoracoscopic), which reduce operative trauma, facilitate faster recovery, and improve postoperative quality of life. Every treatment choice is defined within the GIC – the Multy Disciplinary Team, ensuring a consistent and integrated approach.

As an IRCCS, the Candiolo Cancer Institute integrates clinical practice with a strong commitment for scientific research. Patients may be assessed for inclusion in active clinical trials,

The GIC, Interdisciplinary Care Group, or Multidisciplinary Team, supports the patient at every stage of the care pathway, from diagnosis to treatment and follow-up, with particular attention to nutritional support, psychological well-being, and reintegration into daily life. The organization of check-ups, consultations, and treatments is designed to ensure continuity of care and peace of mind, always placing the human dimension of care at the center.