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In patients with pancreatic cancer, surgery is the primary modality of treatment. Extrapancreatic disease requires palliative therapy and curative resection is not performed in such patients.Patients with unresectable disease are treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy. Curative resection is not contraindicated in all patients with vascular invasion. Involvement of the portal or superior mesenteric vein can be resected and reconstructed with the help of splenic, saphenous or internal jugular veins. However, the involvement of arteries such as the hepatic, celiac or superior mesenteric are contraindications to resection. Various methods of surgical resection may be employed and each of these has its own sets of risks and perioperative complications. The facts are discussed by the patient and surgical team before arriving at a well-informed decision. The method of surgical resection depends on the following features:

• Locally invasive characteristics of the neoplasm
• Size
• Location

Methods of curative resection options include:

• • Distal Pancreatectomy
• Total pancreatectomy
• Pancreaticoduodenectomy, where pylorus may or may not be spared on an individual basis

The National Comprehensive Cancer Network (NCCN) has recommended certain guidelines on resectability of pancreatic neoplasms:

• Patient selection is based on:
  • Resection margins
  • High probability of cure
  • Patient's age
  • Comorbidities

European Society for Medical Oncology (ESMO) has certain guidelines on the treatment of metastatic pancreatic cancer:

• Chemotherapy not preferred
• Gemcitabine is preferred over 5 FU
• Treatment is symptomatic with bypass surgery or stent placement for gastric outlet obstruction or obstructive jaundice

In case of locally advanced disease which is unresectable, the following methods of treatment are preferred: Microwave ablation Photodynamic therapy Irreversible electroporation Photodynamic therapy High-intensity focused ultrasound (HIFU) Iodine-125–cryosurgery Iodine-125 Stereotactic body radiation therapy (SBRT) Radiofrequency ablation (RFA)

CHEMOTHERAPY

Metastatic disease/ Advanced pancreatic cancer which is unresectable: The National Comprehensive Cancer Network (NCCN) has recommended guidelines for treatment in patients based on their performance status. In order to predict survival of patients in various stages of pancreatic cancer, the performance status of a patient is a major prognostic factor. Patients with poor prognostic factors have poor performance status. This includes- Metastatic disease Large tumor Severe weight loss In patients with locally advanced unresectable or metastatic disease with good performance status Preferred treatment: FOLFIRINOX In patients with locally advanced unresectable or metastatic disease with good performance status with intolerance to FOLFIRINOX Preferred treatment:Paclitaxel protein bound+ Gemcitabine In patients with locally advanced unresectable or metastatic disease with poor performance status Preferred treatment: Gemcitabine monotherapy In patients with locally advanced unresectable or metastatic disease with poor performance status refractory to Gemcitabine: Preferred treatment: Capecitabine or capecitabine+erlotinib One year survival of FOLFIRINOX (leucovorin+5-lfuorouracil [LV5-FU]+oxaliplatin+irinotecan)>Gemcitabine One year survival of Gemcitabine+ Erlotinib> Gemcitabine One year survival of Gemcitabine+ Capecitabine≥Gemcitabine One year survival of Gemcitabine+ nanoparticle albumin-bound (nab)-paclitaxel> Gemcitabine

NEW TREATMENTS

Irinotecan in an encapsulated form inside a nanoliposome is being used in advanced pancreatic cancer patients who have been earlier been treated using gemcitabine-based chemotherapy. 

Liposomal Irinotecan is used along with leucovorin and fluorouracil.

ADJUVANT THERAPY The use of gemcitabine as adjuvant therapy is considered a standard form of therapy following surgical resection in pancreatic cancer patients. NEOADJUVANT THERAPY Neoadjuvant therapy may be used as a form of therapy due to the following reasons: Toxic effects of chemotherapy can be tolerated more easily before surgery as compared to after resection Shrinkage of tumor with neoadjuvant therapy makes resection easier and improves patient prognosis Systemic treatment for cancer involving various systems improves prognosis No therapy is considered as first line therapy under this category.Decisions for treatment are made on an individual basis.

SURGERY

Pancreaticoduodenectomy (Whipple Procedure) It is mainly performed for tumors located in: Periampullary region Duodenum Bile duct (Cholangiocarcinoma) Pancreatic duct Head of pancreas Whipple procedure involves removal of the following components due to common blood supply: Stomach antrum Gallbladder Duodenum Head of pancreas After removal of the above structures, the biliary and distal pancreatic ducts are anastomosed to the jejunum to facilitate surgical drainage.

This procedure is associated with several morbidities:

Postoperative abcess Wound infection Anastomotic leak Delay in gastric emptying

Pylorus sparing Whipple procedure: The pylorus may be spared as a modification of Whipple procedure to decrease gastric emptying due to antrectomy. This significantly reduces the incidence of nutritional deficiencies arising from this surgery.

The European Society for Medical Oncology states that the only curative therapy is surgical resection. Ten percent is the five year survival of patients with pancreatic cancer. Patients with node-positive tumors have very poor long term survival.

Distal Pancreatectomy This procedure has a limited use in curative resection of pancreatic cancer. It is mainly performed for tumors located in: Body of pancreas Tail of pancreas This form of surgery has fewer morbidities than the Whipple procedure.

Distal Pancreatectomy involves the following components:

Separation of the distal pancreas bearing the tumor from the normal tissue
Resection of the affected portion

Oversewing of the distal pancreatic duct

This procedure is associated with several morbidities:

Pancreatic endocrine insufficiency Bleeding Leakage of pancreatic stump

Total Pancreatectomy

It is the least preferred due to high mortality rate. It is mainly performed for tumors located in: Neck of the pancreas. Due to involvement of neck, patients develop insulin dependent DM.

PALLIATIVE THERAPY

Pain There are various techniques for pain management as palliative therapy in patients:

Narcotic analgesics Narcotic analgesics+ tricyclic antidepressants/ antiemetics Endoscopic decompression with stent placement in patients with biliary or pancreatic duct obstruction Radiation therapy Neurolysis of the celiac ganglia by many approaches Intraoperative

transgastric
transthoracic 
transabdominal 

Jaundice Obstructive jaundice can present with features of cholangitis: Fever and chills Nausea, vomitting Clay coloured stools Dark urine yellowish discolration of skin pruritus

right upper quadrant pain

Anorexia Preferred treatment in patients: Endoscopic decompression with stent placement in patients with biliary obstruction Techniques of biliary decompression: Cholecystojejunostomy Choledochojejunostomy

Types of stents: Metal- costly, longer lifespan Plastic- cheaper, need replacement every three months

Duodenal obstruction Preferred treatment: Endoscopic stenting of duodenal obstruction Gastrojejunostomy