Why is pancreatic cancer usually inoperable?

Pancreatic cancer

ICD-10-GM-2020 C25.

What does medicine understand by pancreatic cancer?

The pancreas (pancreas) is a gland in the upper abdomen that is visibly divided into three sections. The head of the pancreas (caput pancreatis) rests against the duodenum. There the excretory duct and the main duct of the gallbladder flow into a wart-shaped elevation, the so-called father's papilla (father papilla). Some people have a second small execution corridor, the Santorini corridor. The body of the pancreas (corpus pancreatis) extends towards the spine, the tail of the pancreas (cauda pancreatis) extends towards the spleen.
The pancreas consists of lobules of secretion-producing cells and the surrounding gland ducts (acini). These cells produce digestive enzymes such as amylase for carbohydrate digestion and lipase for fat digestion, which they release directly into the intestines. This forms the exocrine part of the pancreas.

Mainly in the pancreatic body and tail of the pancreas are cells in so-called islets of Langerhans, which produce hormones such as blood sugar regulating insulin and its counterpart glucagon and release them directly into the blood. These are part of the endocrine part of the pancreas. Pancreatic carcinomas, malignant tumors of the pancreas, usually develop in the head of the pancreas, and least of them in the tail.
The most common tumors originate in the exocrine part of the pancreas, especially the gland ducts (ductal adenocarcinomas), such as adenosquamous carcinoma, mucinous non-cystic carcinoma and anaplastic (undifferentiated) carcinoma.
Acinar adenocarcinoma or acinar cell carcinoma develops from the epithelium of the gland cells. Rare cystadenocarcinomas such as mucinous-cystic neoplasia (MCN), intraductal papillary mucinous neoplasia (IPMN), and pancreatic intraepithelial neoplasia (PanIN) arise from cysts.
Neuroendocrine tumors affect the endocrine system of the pancreas and can release hormones themselves. Depending on the hormone, they have specific names such as insulinoma or glucagonoma.

How common is pancreatic cancer and who does it affect?

Pancreatic cancer is a rather rare disease, accounting for around four percent of all cancers. Women and men are equally affected. On average, men become ill at 70 and women at 76.

What stages can pancreatic cancer be divided into?

To assess the disease, the size of the tumor (T1 to T4), how many lymph nodes are affected by cancer cells (N0 to N2) and the formation of distant metastases in other organs (M0 or M1) are used. With this classification, pancreatic cancer can be divided into four stages.
Stage 1
Small tumors (T1 or T2) limited to the pancreas (N0 and M0).
Stage 2
Both larger tumors (T3), which are limited to the pancreas (N0, M0), and smaller tumors (T1 or T2), in which one to three lymph nodes are also involved (N1, M0).
Stage 3
A very large tumor (T4) that has already entered the blood vessels, even if no lymph nodes are demonstrably affected, as well as all tumors (T1-T4) in which more than 4 lymph nodes are affected (N2, M0).
Stage 4
As soon as distant metastases have formed (M1), it is the fourth stage, regardless of the tumor size (T1-T4) and the affected lymph nodes (N0-N2).

What are the symptoms of pancreatic cancer?

Often the patients feel no or only unspecific symptoms for a long time. Many symptoms develop when the tumor has grown into neighboring tissue or presses on a neighboring organ.
Initially, there are abnormal sensations or a feeling of pressure in the upper abdomen, loss of appetite, nausea, digestive problems, depressive moods up to depression or fever. Only later do epigastric pain develop, which sometimes radiate in a belt-shaped manner to the back and intensify when lying on your back.
If the exocrine part is affected, nausea, vomiting and digestive problems or weight loss are common, as the nutrients from food can only be partially absorbed without digestive juices. If the digestion of fat is disturbed, the patients show a fatty stool, it is lightly greasy, sticky or shiny with a pungent odor.
If the tumor presses on the bile duct or closes it, the bile builds up without causing colic first. This leads to yellowing of the skin, mucous and dermis of the eyes, as well as dark coloring of the urine and lightness of the stool, often accompanied by excruciating itching. With the exception of a tumor of the papilla vateri (papillary tumor), predominantly advanced pancreatic carcinomas cause these complaints. At times, the doctor can feel the bulging gallbladder (Courvoisier symbol).
On the one hand, pancreatic cancer can exert pressure on small vessels, which can lead to blood clots (thrombosis) forming. Subsequently, if they become detached, they can lead to an embolism. On the other hand, by influencing thrombokinase, a coagulation factor, there is a higher consumption of platelets and, as a result, a tendency to bleeding (disseminated intravascular coagulopathy, DIC).
If a large tumor in the tail of the pancreas blocks the splenic vein, the spleen can enlarge and form varicose veins in the esophagus and stomach. This can be noticed by bleeding, especially from the esophagus.

Neuroendocrine tumor
Sudden onset of diabetes mellitus can be a sign of a neuroendocrine tumor. An insulinoma can lead to hypoglycaemia, which can manifest itself in sweats, tremors, weakness, fainting and coma.
A scaly, red-brown rash, especially in the groin, buttocks and extremities, as well as a smooth, shiny orange tongue and torn corners of the mouth are characteristic of a glucagonoma. Due to the increase in gastric acid, gastrin-releasing tumors (gastrinomas) often develop gastric ulcers.
If the tumor affects the peritoneum, this can secrete water into the abdomen, which is noticeable in the form of weight gain and an enlarged abdomen. The doctor calls this ascites. Pigmentation rarely occurs on the armpits and groin, but also on the face and hands.
If the solar plexus, fibers and nodes of the autonomic nervous system between the sternum and belly button are affected, excruciating dull pain occurs, which worsens at night and over time. Depending on the location of the metastases, liver enlargement and liver dysfunction, bone pain and neurological symptoms, coughing and shortness of breath can occur.

What are the causes of pancreatic cancer?

The causes of pancreatic cancer are still unknown. There seems to be a genetic predisposition that primarily favors the development of a neuroendocrine tumor.

Which risk factors favor the development of pancreatic cancer?

If two or more cases of pancreatic cancer occur in a close family, the risk of developing it is many times higher (familial pancreatic cancer, FPC). Some hereditary diseases such as Peutz-Jeghers syndrome, cystic fibrosis, or FAMMM syndrome (familial atypical multiple birthmark and melanoma syndrome) increase the likelihood of developing pancreatic cancer. A BRCA-2 mutation, which predominantly causes breast cancer and ovarian cancer, also appears to have an influence.
Chronic inflammation of the pancreas, as well as hereditary pancreatitis, increase the susceptibility to tissue degeneration. If you are overweight or obese, the pancreas can also become chronically inflamed, which increases the risk. People who suffer from diabetes mellitus are also at risk. The active as well as passive consumption of tobacco smoke and alcohol have a major influence.
In addition, a very high-sugar or high-fat diet and frequent consumption of smoked or grilled food are risk factors. Chemicals and toxins such as chromium and chromium compounds, chlorinated hydrocarbons, herbicides, pesticides, solvents (2-naphthylamine, benzidine or benzene derivatives), but also electromagnetic fields and fuel vapors are suspected. An infection with pathogens such as Helicobacter pylori and hepatitis B (or HIV) can also have an influence.

How does the doctor diagnose pancreatic cancer?

At the beginning, the anamnesis takes place, in which the doctor asks about symptoms, previous family illnesses and medication intake. Then the doctor will feel the abdomen for any swelling or hardening. This is followed by various examinations to rule out other diseases and to assess the spread. Inflammation of the pancreas that causes similar symptoms and sometimes occurs at the same time can make diagnosis difficult.
Laboratory examination
The doctor will order a urine, stool and blood test. During the blood test, the doctor tests the pancreatic enzymes trypsin, lipase and amylase, as well as non-specific inflammatory parameters such as CRP, which is often elevated. If a neuroendocrine tumor is suspected, chromogranin A, NSE (neuron-specific enolase), insulin, glucagon, gastrin, VIP (vasoactive intestinal polypeptide) or PP (pancreatic polypeptide) are determined.
Tumor markers are increased in the blood of cancer above a certain tumor size. In the case of pancreatic carcinoma, it is mainly CA19-9, but also CA 50, CA 195, CA 242, CA 72-4, and the CEA (carcinoembryonic antigen). Since even healthy people sometimes have higher tumor markers, they serve less for detection than for the course of the disease.
In addition, imaging methods are available that can depict tumors from a size of one centimeter. The doctor can sometimes determine whether a tumor is operable by visualizing the blood vessels using a contrast medium.

Abdominal ultrasound
In the case of abdominal pain, the first thing to do is an ultrasound examination (sonography). In this way, the doctor can identify the size and composition of the pancreas, liver, gallbladder, stomach and small intestine. However, it is possible that the pancreas cannot be visualized well or that a tumor cannot be identified on it.
Computed tomography (CT)
Using X-rays, a CT can produce detailed sectional images of the pancreas and other structures. In this way, the doctor can recognize metastases in neighboring organs and assess the location, size and operability of a tumor as well as the chances of success. However, very small tumors or changes in the biliary and pancreatic ducts are often not visible with a CT scan.
Magnetic resonance imaging (MRI)
An MRI produces the detailed sectional images with the help of a strong electromagnetic field. This enables the doctor to better differentiate between tumor and pancreatic tissue and to recognize metastases in neighboring organs. With a magnetic resonance cholangiopancreatography (MRCP) the ducts of the pancreas and the bile can be visualized without exposure to radiation.
Endosonography is an endoscopic ultrasound examination in which the doctor inserts a tubular instrument with an ultrasound probe (endoscope) through the mouth and stomach into the duodenum. This enables the doctor to see even the tiniest changes in the tissue and assess the position and size of the tumor and identify possible metastases in the area.
Endoscopic retrograde cholangiopancreatography (ERCP) is a combination of endoscopy and X-ray contrast imaging, which, in contrast to MRCP, involves exposure to radiation. While this examination was often used in the past, it is now only used for unclear findings from CT and MRI or during palliative treatment for the insertion of a stent. A new method is pancreaticoscopy, in which the endoscope can penetrate into the ducts of the pancreas in order to visualize them.
Tissue sample (biopsy)
During an endoscopic ultrasound, the doctor can use a hollow needle to remove a small piece of tissue (fine needle biopsy), which is then examined in the laboratory. Since the biopsy can spread the tumor further, it is only used when imaging results are unclear or to determine palliative treatment.
There is also the liquid biopsy, in which the doctor examines liquids. An early diagnosis of adenocarcinoma can be made by exosomal DNA of the saliva, which enables the doctor to assess the stage and the therapy. If a cyst can form in the pancreas, the doctor can examine the cyst fluid.
In order to detect metastases in neighboring organs, the doctor can order further examinations. A laparoscopy can not only show daughter ulcers in the peritoneum, but also differentiate severe pancreatitis from pancreatic cancer. If the procedure is combined with a laparoscopic ultrasound probe and an abdominal irrigation, the doctor speaks of an extended diagnostic laparoscopy (EDL). The doctor may also order a chest x-ray, skeletal scintigraphy, or positron emission tomography (PET) scan to clarify unclear foci.

What are the treatment options for pancreatic cancer?

The doctor always adapts the treatment individually to the patient. If the tumor is not too large and no metastases have yet formed, the surgeon will operate on the patient and he will also receive chemotherapy. If the tumor is too large or has already affected other organs, it is no longer operable and a cure is no longer possible. The sick person then receives palliative therapy, which reduces their symptoms and improves their quality of life.
Enzyme and hormone therapy
Many patients suffer from protein or vitamin deficiencies, especially fat-soluble vitamins, due to the cancer. But diabetic metabolic disorders can also occur. Since malnutrition and metabolic disorders increase the risk of surgery, the doctor treats them first.
Especially in the case of hormone-producing tumors, the doctor prescribes medication to relieve symptoms. Proton pump inhibitors can be used in gastrinoma to regulate acid production in the stomach. In the case of a glucagonoma, a drug can lower the glucagon level and thus work against the rash and loss of appetite. Zinc ointments can also soothe the rash.
Radiation therapy alone is not a standard treatment for pancreatic cancer. Often times, the doctor will give them chemoradiotherapy, a combination of radiation therapy and chemotherapy. Before the operation, radiotherapy can help shrink the tumor and thus make an operation possible. Radiochemotherapy used after the operation helps with local tumor control and reduces the risk of recurrence, a return of the cancer. However, chemoradiotherapy does not reduce mortality or the risk of metastases.

Targeted therapy
Cancer cells often differ from healthy cells by superficial features or metabolic processes. In targeted cancer therapy, substances are developed that specifically attack cancer cells through these distinguishing features and are therefore more tolerable and effective. These include monoclonal antibodies that attack certain structures on the cell surface or so-called small molecules, such as Erlotinib, that intervene in the metabolism.
Neuroendocrine tumors can also be treated with peptide receptor radionuclide therapy (PRRT). A radioactive atom (radionuclide) is coupled to a certain molecule (ligand) and the doctor finally injects it into the bloodstream.
A new method is irreversible electroporation (IRE), which uses electrical pulses to selectively destroy tumor cells.

How does the surgical removal of the tumor work?

Only a locally limited tumor that has not yet metastasized can be operated on.
If the tumor has formed visible metastases, the doctor stops the operation and takes palliative measures, such as rerouting the bile or placing a stent, a small plastic or metal tube that allows the bile to drain away.
The surgeon removes the tumor over a large area with the adjacent structure. The doctor also removes adjacent lymph nodes in order to examine them for metastases.
If the surgeon has to remove part of the pancreas, this is called a right-sided (pancreatic head), left-sided (pancreatic tail) or middle (pancreatic body) partial resection.
If the doctor has to remove the entire pancreas due to the spread of the tumor, this is called a total resection. In the partial duodenopancreatectomy (Kausch-Whipple operation), the surgeon removes the head of the pancreas, gallbladder and bile duct, duodenum, the lower part of the stomach (pylorus) and parts of the large network (greater omentum, peritoneum).To restore the connections to the digestive system, the doctor sutures the loops of the small intestine to the stomach, pancreatic remains and gallbladder.
As an alternative, the pylorus-preserving pancreatic head resection (pp-Whipple) receives the lower part of the stomach. During a total duodenopancreatectomy, the doctor also removes the pancreatic body, tail and spleen. In most cases, the spleen is also removed together with the tail of the pancreas in a left-sided partial resection.
The doctor can remove benign or very superficial neuroendocrine tumors that are not too close to the duct system by means of enucleation.

How does chemotherapy work for pancreatic cancer?

Cytostatics, the drugs used in chemotherapy, inhibit the reproduction of rapidly dividing cells, such as cancer cells. Neoadjuvant chemotherapy is performed before the operation to reduce the size of a borderline (bipolar) operable tumor. Gemcitabine is used, sometimes in combination with Erlotinib, Oxaliplatin or Capecitabine.
Adjuvant chemotherapy is given within six weeks after the operation, for a period of up to six months, in order to reduce the risk of recurrences and metastases. Gemcitabine is used, in the case of intolerance also 5-fluorouracil and folinic acid. Chemotherapy often has undesirable effects such as nausea, vomiting, weakness or inflammation of the mucous membranes. The patient rarely suffers from severe hair loss.

When is palliative therapy used?

If the tumor is inoperable, there is no longer any chance of a cure. In this case, palliative therapy tries to enable the patient to lead a pain-free life and to improve the quality of life. As part of Best Supportive Care, physicians are permanently available to the terminally ill at any time.
First and foremost is pain therapy, which is often based on the WHO (World Health Organization) level scheme. In the first step, the doctor prescribes non-opioid-containing agents such as paracetamol or acetylsalicylic acid (ASA). If this does not relieve the pain, the doctor combines the medication with weakly effective opioids such as tramadol. Paracetamol or ASA in combination with strong opioids such as morphine show the strongest effect.
As a last step, the doctor can block the celiac plexus plexus in the abdomen so that pain is no longer transmitted to the brain. In addition, there are other measures available that not only relieve pain, but also avoid further complications.
Palliative chemotherapy, depending on the general condition of the patient, can extend the life span and improve the quality of life. Palliative radiation therapy can also be used to relieve pain. As many cancer patients suffer from thrombosis, preventive measures are also part of palliative care.
It is important to have good nutrition for the sick person, as malnutrition leads to weight loss and a shortening of the lifespan. Appropriate diet products are initially used and obstacles in the intestinal passage are surgically removed or kept open by means of an inserted stent. In the further course, liquid food can be introduced into the gastrointestinal tract (enteral feeding) via a feeding tube directly via the mouth or through the abdominal wall using a gastric tube (percutaneous endoscopic gastrostomy EG). With parenteral nutrition, a nutrient solution is administered directly into the blood.
Physiotherapy or a massage can also improve the quality of life of the sick. The patient can also seek help from social workers, pastors, psychologists or self-help groups.

What are the complications of pancreatic cancer?

Pancreatic cancer often causes a disorder of the bile drainage or a blockage of the intestine. The enzyme and hormone production can be disrupted, leading to digestive disorders or diabetes. This is also the case with operations, especially when the pancreas has been completely removed.
Endocrine tumors in particular produce more hormones, which means that the patient can suffer from hypoglycaemia or hypoglycaemia. The increased gastric acid produced in a gastrin-producing tumor can not only lead to gastric or intestinal ulcers, but also cause a gastric or intestinal wall perforation or blocked intestine.

Complications can arise during the operation. These include bleeding and bruising, organ failure, wound healing disorders and infections. The surgeon can injure adjacent organs, nerves or lymph ducts during the operation. Fistulas can create unnatural connections between organs. If an operation scar opens, intestines can escape into the abdominal cavity (suture breakage, incisional hernia). Sutures within the organs can tear or leak (anastomotic leakage).
A typical complication is what is known as dumping. The food pulp is usually left in the stomach for a while. After an operation, however, it immediately passes into the small intestine. This leads to a sharp drop in blood pressure and nausea (early dumping), followed by hypoglycaemia (late dumping).

What is the course of the disease in pancreatic cancer?

The course of the disease differs depending on the type of tumor.
Adenocarcinomas spread quickly and, as they get larger, can spread to surrounding organs such as the duodenum, bile duct, spleen, stomach, or large intestine. The tumor of the head of the pancreas often affects vessels such as the upper mesenteric artery, splenic vein, portal vein or the inferior vena cava. Adenocarcinomas easily metastasize, especially in the liver or the peritoneum (peritoneum) but also in the lungs, bones or other organs. On the other hand, cystadenocarcinomas or endocrine tumors grow more slowly and metastasize more slowly.

What is the prognosis for pancreatic cancer?

With an early diagnosis and complete surgical removal of the tumor, a cure is possible. Since cancer is often discovered late due to the long symptom-free period, its prognosis is generally poor. Of all cancers, this disease has one of the worst survival rates.
Adenocarcinomas, in particular, have a poor prognosis due to their often late diagnosis and rapid growth. After diagnosis, patients live an average of three to five months. Palliative treatment methods also often have little influence on life expectancy. Many tumors respond poorly to chemotherapy, and patients live an average of four to seven months after treatment. In many cases, the tumor returns within two years (relapse) and is then usually inoperable.
Due to their slow growth, endocrine tumors have a better prognosis; the average life expectancy here is four years. Some of these tumors are benign, as is a large proportion of the insulinomas.
A papillary tumor also has a better prognosis, as it is often detected early due to jaundice. And because of their slow growth, cystadenocarcinomas also show a better prognosis and more long-term survivors.

What is the follow-up care for pancreatic cancer?

As follow-up care, a physical examination, blood test and imaging procedures such as ultrasound, CT or MRI take place every three months in the first few years, then at longer intervals. With these examinations, the doctor can identify and treat local recurrences and metastases in good time.
Another part of follow-up care is follow-up treatment (rehabilitation), in which the recovery and recovery process is accelerated, side effects and sequelae are treated and the patient is informed about the diagnosis, therapies and options.
In certain aftercare clinics, chemotherapy can sometimes be carried out. In addition, the sick person learns nutritional and behavioral rules and receives a diet. Removal of part or all of the pancreas can impair digestion or develop diabetes mellitus. Then a lifelong intake of digestive enzymes (pancreatins, fungal enzymes) or diabetes treatment is necessary. In this case, the doctor works out a personal nutrition plan and an individual sports and exercise plan with the patient.
But also psychotherapeutic and social-medical measures such as advice on further working life, home nursing, domestic help and food supply are available to the patient.

How should I eat if I have pancreatic cancer?

After the operation
To relieve the digestion, smaller meals are advisable throughout the day. Saliva contains digestive enzymes, so long chewing is helpful. It is better not to drink while eating, especially avoid alcohol and carbonated drinks and drink water or unsweetened tea instead. Food that is too hot or cold can irritate the stomach and cause diarrhea.

You should avoid flatulent foods such as cabbage, onions, garlic and legumes, but also raw vegetables, as well as heavily smoked, grilled or deep-fried meat and sausage products and high-fat foods. On the other hand, MCT fats (= medium-chain triglycerides) are well tolerated.
Diabetes mellitus
Patients who are diabetic as a result of the illness or surgery must adjust their diet accordingly. The doctor will discuss a nutrition plan with you in terms of fats, carbohydrates and proteins that you should strictly adhere to. Eating regularly and checking your blood sugar regularly will prevent hypoglycemia or hypoglycemia. You can counteract signs of hypoglycaemia with a piece of glucose or a sugar solution. Your doctor will advise you on the doses and intervals of insulin that should be injected before meals.
During chemotherapy
You should avoid acidic or fatty foods, spicy fried foods, coffee and alcoholic beverages as they irritate the stomach lining. You should drink enough to replace the fluid that is lost with diarrhea and vomiting. If you vomit, oral mucosa care and mouth rinses are helpful. Ice or sage tea helps with pain. It is best to eat what you have an appetite for. If you are bothered by certain smells, you can also eat the food cold. High-calorie drinking solutions ("astronaut food") can provide additional nutrients.

Can I prevent pancreatic cancer?

Quitting tobacco and alcohol can reduce the risk of developing pancreatic cancer. A healthy diet rich in fruits and vegetables, high in fiber and vitamins, and regular exercise generally have a positive effect on health.

What consequences does the diagnosis of pancreatic cancer have for those affected and their families?

The diagnosis of cancer often triggers fear and insecurity in those affected, but also in their relatives. Sick people often withdraw from surgery to recover. It is important that patients talk about their illness and also seek advice from their doctor about the illness, therapy and how to deal with the complaints. Sick people, but also their relatives, can exchange ideas with like-minded people in self-help groups or internet forums.

Does the health insurance company pay for the treatment of pancreatic cancer?

The health insurance company covers the costs of all therapies for the treatment of pancreatic cancer. Private clinics or elective doctors are also available for which the health insurance company will reimburse the costs. A deductible may apply. In the case of a longer stay in hospital, you will have to pay a fee per day.

About the author: Dr. med. Christiane Brunner

Specialist in General Medicine

As a general practitioner, my main concern is to support you in the truest sense of the word in your everyday life. What can you do to stay healthy? And how do you get well again if you are ill?

I combine traditional medicine with natural healing methods, acupuncture and massage in order to find the therapy that best suits you and your life situation.

It is particularly important to me that I meet you as a person. At eye level, very direct, close and personal - for uncomplicated coexistence with humor. Because laughter and a small dose of lightness are the best ways to go through life healthily.