After surgery, adjuvant chemotherapy with gemcitabine or 5-FU can be offered if the person is sufficiently fit, after a recovery period of one to two months. In people not suitable for curative surgery, chemotherapy may be used to extend life or improve its quality. Before surgery, neoadjuvant chemotherapy or chemoradiotherapy may be used in cases that are considered to be "borderline resectable" (see Staging) in order to reduce the cancer to a level where surgery could be beneficial. In other cases neoadjuvant therapy remains controversial, because it delays surgery.

Gemcitabine was approved by the United States Food and Drug Administration (FDA) in 1997, after a clinical trial reported improvements in quality of life and a 5-week improvement in median survival duration in people with advanced pancreatic cancer. This was the first chemotherapy drug approved by the FDA primarily for a nonsurvival clinical trial endpoint. Chemotherapy using gemcitabine alone was the standard for about a decade, as a number of trials testing it in combination with other drugs failed to demonstrate significantly better outcomes. However, the combination of gemcitabine with erlotinib was found to increase survival modestly, and erlotinib was licensed by the FDA for use in pancreatic cancer in 2005.

The FOLFIRINOX chemotherapy regimen using four drugs was found more effective than gemcitabine, but with substantial side effects, and is thus only suitable for people with good performance status. This is also true of protein-bound paclitaxel (nab-paclitaxel), which was licensed by the FDA in 2013 for use with gemcitabine in pancreas cancer. By the end of 2013, both FOLFIRINOX and nab-paclitaxel with gemcitabine were regarded as good choices for those able to tolerate the side-effects, and gemcitabine remained an effective option for those who were not. A head-to-head trial between the two new options is awaited, and trials investigating other variations continue. However, the changes of the last few years have only increased survival times by a few months. Clinical trials are often conducted for novel adjuvant therapies.

Palliative care is medical care which focuses on treatment of symptoms from serious illness, such as cancer, and improving quality of life. Because pancreatic adenocarcinoma is usually diagnosed after it has progressed to an advanced stage, palliative care as a treatment of symptoms is often the only treatment possible.

Palliative care focuses not on treating the underlying cancer, but on treating symptoms such as pain or nausea, and can assist in decision-making, including when or if hospice care will be beneficial. Pain can be managed with medications such as opioids or through procedural intervention, by a nerve block on the celiac plexus (CPB). This alters or, depending on the technique used, destroys the nerves that transmit pain from the abdomen. CPB is a safe and effective way to reduce the pain, which generally reduces the need to use opioid painkillers, which have significant negative side effects.

Other symptoms or complications that can be treated with palliative surgery are obstruction by the tumor of the intestines or bile ducts. For the latter, which occurs in well over half of cases, a small metal tube called a stent may be inserted by endoscope to keep the ducts draining. Palliative care can also help treat depression that often comes with the diagnosis of pancreatic cancer.

Both surgery and advanced inoperable tumors often lead to digestive system disorders from a lack of the exocrine products of the pancreas (exocrine insufficiency). These can be treated by taking pancreatin which contains manufactured pancreatic enzymes, and is best taken with food. Difficulty in emptying the stomach (delayed gastric emptying) is common and can be a serious problem, involving hospitalization. Treatment may involve a variety of approaches, including draining the stomach by nasogastric aspiration and drugs called proton-pump inhibitors or H2 antagonists, which both reduce production of gastric acid. Medications like metoclopramide can also be used to clear stomach contents.

The treatment of choice for main-duct IPMNs is resection due to approximately 50% chance of malignancy. Side-branch IPMNs are occasionally monitored with regular CT or MRIs, but most are eventually resected, with a 30% rate of malignancy in these resected tumors. Survival 5 years after resection of an IPMN without malignancy is approximately 80%, 85% with malignancy but no lymph node spread and 0% with malignancy spreading to lymph nodes. Surgery can include the removal of the head of the pancreas (a pancreaticoduodenectomy), removal of the body and tail of the pancreas (a distal pancreatectomy), or rarely removal of the entire pancreas (a total pancreatectomy). In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy or robotic surgery. A study using Surveillance, Epidemiology, and End Result Registry (SEER) data suggested that increased lymph node counts harvested during the surgery were associated with better survival in invasive IPMN patients.

Resection is sometimes a part of a treatment plan, but duodenal cancer is difficult to remove surgically because of the area that it resides in—there are many blood vessels supplying the lower body. Chemotherapy is sometimes used to try to shrink the cancerous mass. Other times intestinal bypass surgery is tried to reroute the stomach to intestine connection around the blockage.

A 'Whipple' procedure is a type of surgery that is sometimes possible with this cancer. In this procedure, the duodenum, a portion of the Pancreas (the head), and the gall bladder are usually removed, the small intestine is brought up to the Pylorus (the valve at the bottom of the stomach) and the Liver and Pancreas digestive enzymes and bile are connected to the small intestine below the Pylorus.

The removal of part of the Pancreas often requires taking Pancreatic Enzyme supplements to aid digestion. These are available in the form of capsules by prescription.

It is not unusual for a patient having received a Whipple procedure to feel perfectly well, and to lead his/her normal life without difficulty.

It is important for the procedure to be performed by a surgeon with extensive experience having done and observed the procedure, as specific competence makes a big difference.

Some patients need to be fitted with tubes to either add nutrients (feeding tubes) or drainage tubes to remove excess processed food that can not pass the blockage.

Surgical treatment is recommended for cats and dogs diagnosed with primary liver tumors but not metastasis to the liver. There are not many treatment options for animals who have multiple liver lobes affected.

These lesions rarely require surgery unless they are symptomatic or the diagnosis is in question. Since these lesions do not have malignant potential, long-term observation is unnecessary. Surgery can include the removal of the head of the pancreas (a pancreaticoduodenectomy), removal of the body and tail of the pancreas (a distal pancreatectomy), or rarely removal of the entire pancreas (a total pancreatectomy). In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy.

Even if the tumor has advanced and metastasized, making curative surgery infeasible, surgery often has a role in neuroendocrine cancers for palliation of symptoms and possibly increased lifespan.

Cholecystectomy is recommended if there is a consideration of long-term treatment with somatostatin analogs.

CUP is a term that refers to many different cancers. For that reason, treatment depends on where the cancer is found, the microscopic appearance of the cancer cells, the biochemical characterization of the cells, and the patient’s age and overall physical condition. In women, who present with axillary lymph node involvement, treatment is offered along the lines of breast cancer. In patients, who have neck lymph node involvement, then treatment is offered along the lines of head and neck cancer. If inguinal lymph nodes are involved, then treatment may be offered along the lines of genitourinary cancer.

If the site of origin is unknown or undiscovered, then the histology of the tumor (e.g., adenocarcinoma, squamous cell or mesenchymal) can usually be identified, and a probable origin may be assumed. When this is possible, then treatment is based on the type of cell and probable origin. Based on histological subtype, combination chemotherapy may be selected. A combination of carboplatin and paclitaxel is often used. Advances techniques such as FISH and tissue of origin testing may also be employed. Germ cell tumors often carry abnormality of chromosome 12, which if identified, directs treatment for metastatic germ cell tumors.

No method is standard for all forms of CUP, but chemotherapy, radiation therapy, hormone therapy, and surgery may be used alone or in combination to treat patients who have CUP. Even when the cancer is unlikely to be cured, treatment may help the patient live longer or improve the patient’s quality of life. Radiation may be used to shrink a variety of local tumors. However, the potential side effects of the treatment must be considered along with the potential benefits.

In CUP to secondary neck nodes, surgery followed by external beam radiotherapy is sufficient.

For CUP with an unfavorable prognosis, treatment with taxanes may provide a slight survival benefit. The uncertainties and ambiguity inherent in a CUP diagnosis may cause additional stress for the patient.

In secretory tumors, somatostatin analogs given subcutaneously or intramuscularly alleviate symptoms by blocking hormone release. A consensus review has reported on the use of somatostatin analogs for GEP-NETs.

These medications may also anatomically stabilize or shrink tumors, as suggested by the PROMID study (Placebo-controlled prospective randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDgut tumors): at least in this subset of NETs, average tumor stabilization was 14.3 months compared to 6 months for placebo.

The CLARINET study (a randomized, double-blind, placebo-controlled study on the antiproliferative effects of lanreotide in patients with enteropancreatic neuroendocrine tumors) further demonstrated the antiproliferative potential of lanreotide, a somatostatin analog and recently approved FDA treatment for GEP-NETS. In this study, lanreotide showed a statistically significant improvement in progression-free survival, meeting its primary endpoint. The disease in sixty five percent of patients treated with lanreotide in the study had not progressed or caused death at 96 weeks, the same was true of 33% of patients on placebo. This represented a 53% reduction in risk of disease progression or death with lanreotide based on a hazard ratio of .47.

Lanreotide is the first and only FDA approved antitumor therapy demonstrating a statistically significant progression-free survival benefit in a combined population of patients with GEP-NETS.

Other medications that block particular secretory effects can sometimes relieve symptoms.

ACC can be treated with a Whipple procedure or (depending on the location within the pancreas) with left partial resection of pancreas.

The cancerous mass tends to block food from getting to the small intestine. If food cannot get to the intestines, it will cause pain, acid reflux, and weight loss because the food cannot get to where it is supposed to be processed and absorbed by the body.

Patients with duodenal cancer may experience abdominal pain, weight loss, nausea, vomiting, and chronic GI bleeding.

Most people with cancer of unknown primary origin have widely disseminated and incurable disease, although a few can be cured through treatment. With treatment, typical survival with CUP ranges from 6 to 16 months. Survival rates are lower in cases with visceral metastatic disease, ranging from 6 to 9 months. Survival rates are higher when the cancer is more limited to lymph nodes, pleura, or peritoneal metastasis, which ranges from 14 to 16 months. Long-term prognosis is somewhat better if a particular source of cancer is strongly suggested by clinical evidence.

The different treatment options for management of chronic pancreatitis are medical measures, therapeutic endoscopy and surgery. Treatment is directed, when possible, to the underlying cause, and to relieve pain and malabsorption. Insulin dependent diabetes mellitus may occur and need long term insulin therapy. The abdominal pain can be very severe and require high doses of analgesics, sometimes including opiates. Alcohol cessation and dietary modifications (low-fat diet) are important to manage pain and slow the calcific process. Antioxidants may help but it is unclear if the benefits are meaningful.

A low fat diet is indicated. The use of drugs which are known to have an association with pancreatitis should be avoided. Some patients benefit from the use of pancreatic enzymes on a supplemental basis. One study indicated that 57 percent of dogs, who were followed for six months after an acute pancreatitis attack, either continued to exhibit inflammation of the organ or had decreased acinar cell function, even though they had no pancreatitis symptoms.

There are no approved treatments for canine pancreatitis. Treatment for this disease is supportive, and may require hospitialization to attend to the dog's nutritional and fluid needs, pain management, and addressing any other disease processes (infection, diabetes, etc.) while letting the pancreas heal on its own. Treatment often involves "resting" the pancreas for a short period of time by nil per os/nothing per os (NPO)/nil by mouth (NBM), in which the patient receives no food or fluids by mouth, but is fed and hydrated by intravenous fluids and a feeding tube. Dehydration is also managed by the use of fluid therapy. However, a specialist from Texas A&M University has stated "There is no evidence whatsoever that withholding food has any beneficial effect." Other specialists have agreed with his opinion.

Canine pancreatitis is complex, often limiting the ability to approach the disease.

For treatment purposes, MCACL has been traditionally considered a non-small cell lung carcinoma (NSCLC). Complete radical surgical resection is the treatment of choice.

There is virtually no data regarding new molecular targets or targeted therapy in the literature to date. Iwasaki and co-workers failed to find mutations of the epidermal growth factor receptor (EGFR) or the cellular Kirsten rat sarcoma virus oncogene "K-ras" in one reported case.

Pancreatic enzyme replacement is often effective in treating the malabsorption and steatorrhea associated with chronic pancreatitis. Treatment of CP consists of administration of a solution of pancreatic enzymes with meals. Some patients do have pain reduction with enzyme replacement and since they are relatively safe, giving enzyme replacement to a chronic pancreatitis patient is an acceptable step in treatment for most patients. Treatment may be more likely to be successful in those without involvement of large ducts and those with idiopathic pancreatitis.

The treatment of pancreatitis is supportive and depends on severity. Morphine generally is suitable for pain control. There are no clinical studies to suggest that morphine can aggravate or cause pancreatitis or cholecystitis.

The treatment that is received for acute pancreatitis will depend on whether the diagnosis is for the mild form of the condition, which causes no complications, or the severe form, which can cause serious complications.

Severe pancreatitis can cause organ failure, necrosis, infected necrosis, pseudocyst, and abscess. If diagnosed with severe acute pancreatitis, people will need to be admitted to a high dependency unit or intensive care unit. It is likely that the levels of fluids inside the body will have dropped significantly as it diverts bodily fluids and nutrients in an attempt to repair the pancreas. The drop in fluid levels can lead to a reduction in the volume of blood within the body, which is known as hypovolemic shock. Hypovolemic shock can be life-threatening as it can very quickly starve the body of the oxygen-rich blood that it needs to survive. To avoid going into hypovolemic shock, fluids will be pumped intravenously. Oxygen will be supplied through tubes attached to the nose and ventilation equipment may be used to assist with breathing. Feeding tubes may be used to provide nutrients, combined with appropriate analgesia.

As with mild acute pancreatitis, it will be necessary to treat the underlying cause—gallstones, discontinuing medications, cessation of alcohol, etc. If the cause is gallstones, it is likely that an ERCP procedure or removal of the gallbladder will be recommended. The gallbladder should be removed during the same hospital admission or within two weeks of pancreatitis onset so as to limit the risk of recurrent pancreatitis. If the cause of pancreatitis is alcohol, cessation of alcohol consumption and treatment for alcohol dependency may improve pancreatitis. Even if the underlying cause is not related to alcohol consumption, doctors recommend avoiding it for at least six months as this can cause further damage to the pancreas during the recovery process. Oral intake, especially fats, is generally restricted initially but early enteral feeding within 48 hours has been shown to improve clinical outcomes. Fluids and electrolytes are replaced intravenously. Nutritional support is initiated via tube feeding to surpass the portion of the digestive tract most affected by secreted pancreatic enzymes if there is no improvement in the first 72–96 hours of treatment.

The production of pancreatic enzymes is suppressed by restricting the patient's oral intake of food patient in conjunction with the use of long-acting somatostatin analogues. The patient's nutrition is maintained by total parenteral nutrition.

This treatment is continued for 2–3 weeks, and the patient is observed for improvement. If no improvement is seen, the patient may receive endoscopic or surgical treatment. If surgical treatment is followed, an ERCP is needed to identify the site of the leak.

Fistulectomy is done in which the involved part of the pancreas is also removed.

Periampullary cancer is a cancer that forms near the ampulla of Vater, an enlargement of the ducts from the liver and pancreas where they join and enter the small intestine.It consists of:

1. ampullary tumour from ampulla of Vater,

2. cancer of lower common bile duct, and

3. duodenal cancer adjacent to ampulla.

4. carcinoma head of pancreas

It presents with painless jaundice which may have waxing and waning nature because at times the sloughing of the tumor tissue relieves the obstruction partially.

Treatment usually is bypassing the obstructed segment of duodenum by duodeno-jejunostomy. Another approach is laparoscopic gastrojejunostomy or duodenojejunostomy.

Resection of the polyps is required only if serious bleeding or intussusception occurs. Enterotomy is performed for removing large, single nodules. Short lengths of heavily involved intestinal segments can be resected. Colonoscopy can be used to snare the polyps if they are within reach.

Treatment of accessory pancreas depends on the location and extent of the injured tissue. Surgery may be an option, or some physicians order prophylactic antibiotics.

Pancreatic pseudocyst treatment should be aimed at avoiding any complication (1 in 10 cases become infected). They also tend to rupture, and have shown that larger cysts have a higher likelihood to become more symptomatic, even needing surgery. If no signs of infection are present, initial treatment can include conservative measures such as bowel rest (NPO), parenteral nutrition (TPN), and observation. Serum amylase levels can be trended. If symptoms do not improve by 6 weeks, surgical intervention may be appropriate.

In the event of surgery:

- Cystogastrostomy: In this surgical procedure a connection is created between the back wall of the stomach and the cyst such that the cyst drains into the stomach.

- Cystjejunostomy: In this procedure a connection is created between the cyst and the small intestine so that the cyst fluid directly into the small intestine.

- Cystduodenostomy: In this procedure a connection is created between the duodenum (the first part of the intestine) and the cyst to allow drainage of the cyst content into duodenum. The type of surgical procedure depends on the location of the cyst. For pseudocysts that occur in the head of the pancreas a cystduodenostomy is usually performed.