Pancreatic cancer occurs when cells in the pancreas, the organ of the gland behind the stomach, begin to multiply out of control and form a mass. These cancer cells have the ability to attack other parts of the body. There are a number of types of pancreatic cancer. The most common, pancreatic adenocarcinoma , accounts for about 85% of cases, and the term "pancreatic cancer" is sometimes used to refer only to that type. This adenocarcinoma begins in the pancreas that makes the digestive enzymes. Several other types of cancers, which collectively represent the majority of non-adenocarcinoma, can also arise from these cells. One to two percent of cases of pancreatic cancer are neuroendocrine tumors, which arise from pancreatic cells that produce hormones. It is generally less aggressive than pancreatic adenocarcinoma.
The signs and symptoms of the most common forms of pancreatic cancer may include yellow skin, stomach or backache, unexplained weight loss, light colored benches, dark urine and loss of appetite. There is usually no symptoms in the early stages of the disease, and symptoms that are specific enough to show pancreatic cancer usually do not develop until the disease has reached an advanced stage. At the time of diagnosis, pancreatic cancer has often spread to other parts of the body.
Pancreatic cancer is rare before the age of 40, and more than half of cases of pancreatic adenocarcinoma occur in those over the age of 70 years. Risk factors for pancreatic cancer include tobacco smoking, obesity, diabetes, and certain rare genetic conditions. Approximately 25% of cases are associated with smoking, and 5-10% are associated with inherited genes. Pancreatic cancer is usually diagnosed with a combination of medical imaging techniques such as ultrasound or computed tomography, blood tests, and tissue sample examination (biopsy). The disease is divided into several stages, from the beginning (stage I) to the end (stage IV). General population screening has not been proven effective.
The risk of developing pancreatic cancer is lower among non-smokers, and people are maintaining a healthy weight and limiting the consumption of red or processed meats. Smokers' opportunities to develop the disease decline if they quit smoking, and almost return to other populations after 20 years. Pancreatic cancer can be treated by surgery, radiotherapy, chemotherapy, palliative care, or a combination of these. Treatment options are based in part on the stage of cancer. Surgery is the only treatment that can cure pancreatic adenocarcinoma, and may also be done to improve quality of life without healing potential. Treatment of pain and medication to improve digestion is sometimes necessary. Early palliative care is recommended even for those who receive treatments that aim to heal.
In 2015, pancreatic cancer of all types results in 411,600 deaths globally. Pancreatic cancer is the fifth most common cause of cancer death in the UK, and the fourth most common in the United States. The disease is most common in developed countries, where about 70% of new cases in 2012 come from. Pancreatic adenocarcinoma usually has a very poor prognosis: after diagnosis, 25% of people survive a year and 5% live for five years. For cancers diagnosed early, a five-year survival rate rises to about 20%. Neuroendocrine cancer has better results; at five years of diagnosis, 65% of those diagnosed live, although survival varies depending on the type of tumor.
Video Pancreatic cancer
Type
Many types of pancreatic cancers can be divided into two general groups. Most cases (about 99%) occur in parts of the pancreas that produce digestive enzymes, known as exocrine components. There are several sub-types of exocrine pancreatic cancer, but their diagnosis and treatment have many similarities. A small minority of cancers that appear in the pancreatic hormone-producing tissue (endocrine) have different clinical characteristics. Both groups occur primarily (but not exclusively) in people over 40, and are slightly more common in men, but some rare sub-species mainly occur in women or children.
Exocrine cancer
The exocrine group is dominated by pancreatic adenocarcinoma (variations of this name can add "invasive" and "ductal"), which are by far the most common type, representing about 85% of all pancreatic cancers. Almost all of this begins in the pancreatic duct, such as pancreatic ductal adenocarcinoma (PDAC). This is despite the fact that the tissue from which it arises - the epithelium of the pancreatic ducts - represents less than 10% of the pancreas by the cell volume, since it only forms a channel (a broad channel system but capillaries like to flutter out) in the pancreas. This cancer comes from a channel carrying secretions (such as enzymes and bicarbonates) from the pancreas. Approximately 60-70% of adenocarcinomas occur in the pancreas head.
The next most common type, pancreatic acellar cell carcinoma, appears in the cell group that produces these enzymes, and represents 5% of exocrine pancreatic cancer. As with the 'functioning' endocrine cancer described below, carcinoma of acinar cells can lead to overproduction of certain molecules, in this case digestive enzymes, which can cause symptoms such as skin rashes and joint pain.
Cystadenocarcinomas account for 1% of pancreatic cancers, and they have a better prognosis than other exocrine types.
Pancreatoblastoma is a rare form, most common in childhood, and with a relatively good prognosis. Other exocrine cancers include adenosquamous carcinoma, stem cell carcinoma, hepatoid carcinoma, colloid carcinoma, undifferentiated carcinoma, and undifferentiated carcinoma with osteoclast-like giant cells. Solid pseudopapillary tumors are rare low-grade neoplasms that primarily affect young women, and generally have a very good prognosis.
Cystic pancreatic pancreatic neoplasms are a widespread group of pancreatic tumors that have various malignant potentials. They are detected at a very increased rate because CT scans become more powerful and common, and discussions continue as the best way to assess and treat them, given that many are benign.
Neuroendocrine
A small percentage of tumors that appear elsewhere in the pancreas are pancreatic neuroendocrine tumors (PanNETs). Neuroendocrine tumors (NETs) are a diverse group of benign or malignant tumors that arise from the body's neuroendocrine cells, which are responsible for integrating the nervous and endocrine systems. NET can start in most organs of the body, including pancreas, where various types of malignant are all considered rare. Pannets are grouped into 'functioning' and 'not functioning' types, depending on the extent to which they produce hormones. Types that serve to secrete hormones such as insulin, gastrin, and glucagon into the bloodstream, often in large quantities, resulting in serious symptoms such as low blood sugar, but also support relatively early detection. The most common PanNET functions are insulinomas and gastrinomas, named after the hormones they secrete. The non-functioning type does not secrete enough hormones to produce clear clinical symptoms. For this reason, non-functioning PanNET is often diagnosed only after the cancer has spread to other parts of the body.
Like other neuroendocrine tumors, the history of the terminology and classification of PanNET is very complex. Pannets are sometimes called "cancer celllets", although it is now known that they do not actually arise from islet cells as previously thought.
Maps Pancreatic cancer
Signs and symptoms
Since pancreatic cancer usually does not cause symptoms that can be recognized in the early stages, the disease is usually not diagnosed until it has spread beyond the pancreas itself. This is one of the main reasons for the generally poor survival rate. The exception to this is the functioning PanNET, where excessive production of various active hormones can cause symptoms (which depend on the type of hormone).
Given that the disease is rarely diagnosed before the age of 40 years, the common symptoms of pancreatic adenocarcinoma occurring prior to diagnosis include:
- Pain in the upper abdomen or back, often spreading from around the belly to the back. The location of the pain may indicate the part of the pancreas where the tumor is located. The pain can worsen at night and may increase over time to become severe and unrelenting. It may be a little relieved to lean forward. In the UK, about half of new cases of pancreatic cancer are diagnosed after a visit to the hospital's emergency department for sickness or jaundice. In up to two thirds of people with abdominal pain are the main symptoms, amounting to 46% of the total with jaundice, with 13% suffering from painless yellow pain.
- Jaundice, yellow on the whites of the eyes or skin, with or without pain, and possibly in combination with dark urine. This occurs when the cancer in the pancreas head blocks the bile ducts as it travels through the pancreas.
- Unexplained weight loss, either due to loss of appetite, or loss of exocrine function resulting in poor digestion.
- The tumor can hit the adjacent organs, interfere with the digestive process and make it difficult for the stomach to empty, which can cause nausea and feeling full. Undigested fat causes fat and foul-smelling stools that are difficult to water. Constipation is common.
- At least 50% of people with pancreatic adenocarcinoma have diabetes at the time of diagnosis. While long-standing diabetes is a known risk factor for pancreatic cancer (see risk factors), cancer itself can cause diabetes, in which case recent diabetes onset can be considered an early sign of the disease. People over the age of 50 who have diabetes are eight times more likely to have pancreatic adenocarcinoma risk within three years, after which the relative risk decreases.
Other findings
- Trousseau's syndrome, in which blood clots form spontaneously in the portal vein, veins in the extremities, or superficial veins anywhere on the body, may be linked to pancreatic cancer, and is found in about 10% of cases.
- Clinical depression has been reported to be associated with pancreatic cancer in about 10-20% of cases, and may be a barrier to optimal management. Depression sometimes appears before a cancer diagnosis, suggesting that it may be caused by the biology of the disease.
Other common manifestations of the disease include: weakness and fatigue; dry mouth; sleep problems; and a clear abdominal mass. "
Symptoms of deployment
The spread of pancreatic cancer to other organs (metastasis) can also cause symptoms. Usually, the first pancreatic adenocarcinoma spreads to the nearby lymph nodes, and then to the liver or to the peritoneal, colon or lung cavity. It is not common to spread to bone or brain.
Cancer in the pancreas can also become secondary cancer that has spread from other parts of the body. It is not uncommon, found only about 2% of cases of pancreatic cancer. Kidney cancer is the most common cancer to spread to the pancreas, followed by colorectal cancer, and then skin, breast, and lung cancers. Surgery can be performed on the pancreas in such cases, whether in the hope of a drug or to relieve symptoms.
Risk factors
Risk factors for pancreatic adenocarcinoma include:
- Age, sex and ethnicity; the risk of developing pancreatic cancer increases with age. Most cases occur after age 65, while cases before age 40 are not common. The disease is slightly more common in men than women, and in the United States is more than 1.5 times more common in African Americans, although incidents in Africa are low.
- Smoking is the most established avoided risk factor for pancreatic cancer, roughly double the risk among long-term smokers, the risk of increasing the number of cigarettes smoked and the years of smoking. The risk decreases slowly after quitting smoking, taking about 20 years to return to almost all non-smokers.
- Obesity; A BMI greater than 35 increases the relative risk by about half.
- Family history; 5-10% of pancreatic cancer cases have an inherited component, in which people have a family history of pancreatic cancer. The risk is greatly increased if more than one first-degree relative suffers from the disease, and more simply if they develop it before the age of 50 years. Most of the genes involved have not been identified. Hereditary pancreatitis provides an increased lifetime risk of pancreatic cancer 30-40% to 70 years of age. Screening for early pancreatic cancer may be offered to individuals with hereditary pancreatitis based on research. Some people may choose to have their pancreas surgically removed to prevent cancer developing in the future.
- Pancreatic cancer has been associated with other rare hereditary syndromes: Peutz-Jeghers syndrome due to mutations in the tumor suppressor gene STK11 (very rare, but very strong risk factors); dysplastic naevus syndrome (or familial multiple atypical mole and melanoma syndrome, FAMMM-PC) due to mutations in tumor suppressor gene CDKN2A ; autosomal recessive ataxia-telangiectasia and autosomal dominant on mutations in the BRCA2 and PALB2 genes; hereditary non-polyposis colon cancer (Lynch syndrome); and familial adenomatous polyposis. PanNET has been associated with some type 1 endocrine neoplasia (MEN1) and von Hippel Lindau syndrome.
- Chronic pancreatitis seems to risk almost three times as much, and as with diabetes, new onset pancreatitis may be a symptom of a tumor. The risk of pancreatic cancer in individuals with family pancreatitis is very high.
- Diabetes mellitus is a risk factor for pancreatic cancer and (as noted in Signs and symptoms) of new onset diabetes can also be an early sign of disease. People who have been diagnosed with Type 2 diabetes for more than ten years may have a 50% increased risk, compared with non-diabetics.
- Certain foods (different from obesity) have not been clearly shown to increase the risk of pancreatic cancer. Food factors that contain little evidence of increased risks include processed meats, red meat and meat cooked at very high temperatures (eg by frying, grilling or roasting).
Alcohol
Excessive drinking of alcohol is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer. However, many studies fail to establish alcohol consumption as a direct risk factor for pancreatic cancer. Overall, these associations are consistently weak and the majority of studies have found no relationship, with strong confounding factor factors. Stronger evidence for a relationship with heavy drinking, at least six drinks per day.
Pathophysiology
Precancer
Exocrine cancer is thought to arise from certain types of precancerous lesions in the pancreas. However, these lesions do not necessarily develop into cancer, and the increase in detectable amounts as a by-product of increased use of CT scans for other reasons is not all handled. Regardless of serous cystadenoma of the pancreas (SCN), which is almost always benign, four types of precancerous lesions are recognized.
The first is pancreatic intraepithelial neoplasia. These lesions are microscopic abnormalities in the pancreas and are often found in autopsies of people who are not diagnosed with cancer. These lesions can progress from low to high levels and then to tumors. Over 90% of cases in all classes carry the wrong KRAS genes, while in grades 2 and 3 destroy three more genes - CDKN2A ( p16 ), p53 and SMAD4 - are increasingly being found.
The second type is intrumuctal mucinous neoplasms (IPMNs). This is a macroscopic lesion, which is found in about 2% of all adults. This number increased to ~ 10% at the age of 70 years. These lesions have about 25% risk of developing into invasive cancer. They may have gene mutations KRAS (~ 40-65% of cases) and in the GNAS subgroup Gs alpha and RNF43, affect the Wnt signaling pathway. Even if surgically removed, there is an increased risk of developing pancreatic cancer afterwards.
The third type, melancholic cystic neoplasms (MCNs) mainly occurs in women, and may remain benign or develop into cancer. If these lesions become large, cause symptoms, or have suspicious features, they are usually successfully removed surgically.
The fourth type of cancer that appears in the pancreas is the intraductal tubulopapillary neoplasm. This species is recognized by WHO in 2010 and represents about 1-3% of all pancreatic neoplasms. The mean age at diagnosis was 61 years (range 35-78 years). Approximately 50% of these lesions become invasive. Diagnosis depends on histology because the lesion is very difficult to distinguish from other lesions either on a clinical or radiological basis.
Invasive cancer
Genetic events found in ductal adenocarcinoma have been well characterized, and complete exhaust sequencing has been performed for common tumor types. Four genes each have been found to mutate in the majority of adenocarcinoma:
KRAS (in 95% of cases), CDKN2A (also in 95%), TP53 (75%), and SMAD4 (55%). The latter is particularly associated with a poor prognosis. SWI/SNF mutation/removal occurs in about 10-15% adenocarcinoma. Genetic changes in some types of pancreatic cancer and precancerous lesions have also been investigated. Transcripticomicrobial analysis and mRNA sequencing for common forms of pancreatic cancer have found that 75% of human genes are expressed in tumors, with about 200 genes more specifically expressed in pancreatic cancer than other types of tumors.
PanNet
The genes that are commonly found to mutate in PanNet are different from those of the genes in exocrine pancreatic cancer. For example,
KRAS mutations are not usually there. Instead, hereditary gene mutations MEN1 cause MEN1 syndrome, in which the primary tumor occurs in two or more endocrine glands. About 40-70% of people born with MEN1 mutations eventually developed PanNet. Other genes that often mutate include DAXX , mTOR and ATRX .
Diagnosis
The symptoms of pancreatic adenocarcinoma usually do not appear in the early stages of the disease, and individually are not typical for the disease. The symptoms at diagnosis vary according to the location of the cancer in the pancreas, the anatomists divide (from left to right on most diagrams) into the thick head, neck, and oval body, ending in the tail.
Regardless of the location of the tumor, the most common symptom is unexplained weight loss, which may be quite large. Most minorities (between 35% and 47%) of people diagnosed with this disease will experience nausea, vomiting or feelings of weakness. Tumors in the head of the pancreas usually also cause jaundice, pain, loss of appetite, dark urine, and light colored stools. Tumors in the body and tail usually cause pain.
People sometimes have a new onset of atypical type 2 diabetes that is difficult to control, a history of recent but unexplained inflammation of blood vessels caused by blood clots (thrombophlebitis) known as Trousseau markers, or previous pancreatitis attacks. A doctor can predict pancreatic cancer when the onset of diabetes in someone over 50 years accompanied by typical symptoms such as unexplained weight loss, persistent abdominal pain or back, indigestion, vomiting, or fatty feces. Jaundice accompanied by a painless gall bladder (known as the Courvoisier sign) can also raise suspicion, and may help differentiate pancreatic cancer from gallstones.
Medical imaging techniques, such as computed tomography (CT scan) and endoscopic ultrasound (EUS) are used both to confirm the diagnosis and to help decide whether a tumor can be removed by "resectability". In contrast contrast CT scans, pancreatic cancer usually shows a gradual increase in radiocontrasion, rather than rapid washing as seen in normal pancreas or delayed cessation as seen in chronic pancreatitis. Magnetic resonance imaging and positron emission tomography can also be used, and magnetic resonance of cholangiopancreatography may be useful in some cases. Ultrasound stomach is less sensitive and will miss small tumors, but can identify cancer that has spread to the liver and fluid accumulation in the peritoneal cavity (ascites). This can be used for a quick first check and cheap before any other technique.
Biopsies with fine needle aspiration, often guided by endoscopic ultrasound, may be used if there is uncertainty over the diagnosis, but histologic diagnosis is usually not necessary to remove the tumor by surgery to continue.
Liver function tests may show a combination of indications of bile duct obstruction (increased conjugated bilirubin, -glutamyl transpeptidase and alkaline phosphatase levels). CA19-9 (carbohydrate antigen 19,9) is a tumor marker that often increases in pancreatic cancer. However, it lacks sensitivity and specificity, at least because 5% of people do not have Lewis (a) antigen and can not produce CA19-9. It has an 80% sensitivity and a specificity of 73% in detecting pancreatic adenocarcinoma, and is used to follow a known case rather than a diagnosis.
The most common form of pancreatic cancer (adenocarcinoma) is usually characterized by slightly different glandular structures on microscopic examination. There is usually desmoplasia or formation of solid fibrous stroma or structural tissue consisting of various cell types (including myofibroblasts, macrophages, lymphocytes and mast cells) and stored materials (such as type I collagen and hyaluronic acid). This creates a tumor microenvironment that lacks blood vessels (hypovascular) and oxygen (hypoxia tumors). It is thought that this prevents many chemotherapy drugs to reach the tumor, as one of the factors that make cancer extremely difficult to treat.
Staging
Exocrine cancer
Pancreatic cancer is usually staged after a CT scan. The most widely used cancer staging system for pancreatic cancer is defined by the American Joint Committee on Cancer (AJCC) together with the Union for International Cancer Control (UICC). The AJCC-UICC staging system establishes four major stages in its entirety, from early to advanced illness, based on the TNB T umor size, spreading to lymph n , and M etastasis.
To help decide treatment, the tumor is also divided into three broader categories based on whether surgical removal seems likely: in this way, the tumor is considered "inoperable", "operable", or "unresectable". When the disease is still in its early stages (AJCC-UICC stage I and II), without spreading to large blood vessels or remote organs such as the liver or lungs, tumor surgical resection is usually possible, if the patient is willing to undergo this major surgery and is considered adequate corresponding. The AJCC-UICC staging system allows the distinction between stage III tumors rated "borderline resectable" (where surgery is technically feasible because the celiac axes and superior mesenteric arteries are still free) and those "inoperable" (as more advanced local disease ); in the more detailed classification of the TNM, these two groups correspond to T3 and T4 respectively.
- Pancreatic cancer staging (TNM classification)
Localized advanced adenocarcinoma has spread to the neighboring organs, which may be one of the following (in decreasing frequency sequence): duodenum, stomach, transverse colon, spleen, adrenal gland, or kidney. Very often they also spread to blood vessels or lymphatic and important nerves that run close to the pancreas, making surgery much more difficult. Typical sites for metastatic spread (stage IV disease) are the liver, the peritoneal cavity and the lungs, all of which occur in 50% or more of fully developed cases.
PanNet
The WHO 2010 classification of digestive system tumors assessed all pancreatic neuroendocrine tumors (PanNet) into three categories, based on their cellular differentiation levels (from "NET G1" to "NET G3" badly differentiated). The US National Comprehensive Cancer Network recommends the use of the same AJCC-UICC staging system as pancreatic adenocarcinoma. Using this scheme, the step-by-step results for PanNet are not the same as exocrine cancer. The different TNM systems for PanNet have been proposed by the European Neuroendocrine Tumor Society.
Prevention and filtering
In addition to not smoking, the American Cancer Society recommends maintaining a healthy weight, and increasing consumption of fruits, vegetables, and whole grains, while reducing consumption of red and processed meat, although no consistent evidence will prevent or reduce pancreatic cancer special.. A review of the study in 2014 concluded that there is evidence that consumption of citrus fruits and curcumin reduces the risk of pancreatic cancer, while there may be beneficial effects of grains, folate, selenium, and fish that are not fried.
In the general population, large-scale screening is currently considered ineffective, although newer techniques, and highly targeted group screening, are being evaluated. However, routine examination with endoscopy ultrasound and MRI/CT imaging is recommended for those at high risk of genetics inherited.
Management
Exocrine cancer
A key assessment done after diagnosis is whether surgical removal of the tumor is possible (see Staging), as this is the only cure for this cancer. Whether or not surgical resection can be offered depends on how much the cancer has spread. The exact location of the tumor is also a significant factor, and CT can show how it relates to the major blood vessels passing near the pancreas. The general health of the person should also be assessed, even though age itself is not an obstacle to surgery.
Chemotherapy and, to a lesser extent, radiotherapy is likely to be offered to most people, whether or not surgery is possible. Specialists suggest that pancreatic cancer management should be in the hands of multidisciplinary teams including specialists in some aspects of oncology, and therefore, best done in larger centers.
Surgery
Surgery with the goal of healing is possible only in about one fifth (20%) of new cases. Although CT scans help, in practice it can be difficult to determine if the tumor can be completely removed (resectability), and that may only become apparent during surgery that is unlikely to successfully remove the tumor without damaging other vital tissues.. Whether surgical resection can be offered or not depends on a variety of factors, including the exact level of precise local anatomy for, or involvement, venous or arterial blood vessels, and surgical skills and careful consideration of projected postoperative recovery. The age of the person himself is not an excuse not to operate, but their general performance status should be adequate for major operations.
One of the special features evaluated is the exhilarating presence, or absenteeism, of a clear layer or the area of ​​fat that creates a barrier between the tumor and the blood vessels. Traditionally, the assessment was made of tumor proximity to the venous or primary artery, in terms of "abutment" (defined as the tumor touching no more than half the circumference of the nonfat blood vessels to separate it), "wrapping" (when the tumor encloses most of the vessel blood), or full vessel involvement. Resections that include fragmented blood vessel sections are possible in some cases, especially if early neoadjuvant therapy is feasible, using chemotherapy and/or radiotherapy.
Even when surgery appears to have worked, cancer cells are often found around the edge ("margin") of the removed tissue, when a pathologist checks them microscopically (this will always be done), indicating the cancer has not been completely removed.. Furthermore, cancer stem cells usually do not appear microscopically, and if they exist, they can continue to grow and spread. Exploratory laparoscopy (small surgical procedure with camera guidance) can be done to get a clearer picture of the results of full surgery.
For cancer involving the pancreas head, Whipple procedure is the most common curative surgical treatment. This is a major surgery involving the taking of the pancreatic head and the duodenum duodenum joint ("pancreato-duodenectomy"), making a bypass for food from the stomach to the jejunum ("gastro-jejunostomy") and attaching the jejunal coil. to the cystic ducts to drain the bile ("cholecysto-jejunostomy"). This can be done only if the person is likely to survive a major surgery and if the cancer is localized without invading local structures or metastases. Therefore, it can be done only in a small number of cases. Pancreatic tail cancer can be resected using a procedure known as distal pancreatectomy, which often involves removal of the spleen. Currently, this can often be done using minimally invasive surgery.
Although curative surgery no longer required a very high mortality rate that occurred until the 1980s, most people (about 30-45%) still had to be treated for post-operative disease not caused by cancer itself. The most common complication of surgery is difficulty in emptying the abdomen. More limited surgical procedures may also be used to relieve symptoms (see palliative care): for example, if the cancer attacks or suppresses the duodenum or colon. In such cases, bypass surgery can overcome obstruction and improve quality of life but is not intended as a drug.
Chemotherapy
After surgery, adjuvant chemotherapy with gemcitabine or 5-FU may be offered if the person is fit enough, after a one to two month recovery period. In people who are not suitable for curative surgery, chemotherapy may be used to prolong life or improve its quality. Prior to surgery, neoadjuvant chemotherapy or chemoradiotherapy may be used in cases considered "resectable limits" (see Staging) to reduce cancer to levels where surgery can be beneficial. In other cases neoadjuvant therapy is still controversial, because it delayed surgery.
Gemcitabine was approved by the US Food and Drug Administration (FDA) in 1997, after clinical trials reported improved quality of life and a 5-week increase in median duration duration in people with advanced pancreatic cancer. This is the first chemotherapy drug approved by the FDA especially for the end point of nonsurvival clinical trials. Chemotherapy using gemcitabine alone is standard for about a decade, as a number of trials tested in combination with other drugs failed to show much better results. However, the combination of gemcitabine with erlotinib was found to improve survival simply, and erlotinib was licensed by the FDA for use in pancreatic cancer in 2005.
FOLFIRINOX chemotherapy regimens using four drugs are found to be more effective than gemcitabine, but with considerable side effects, and are therefore only suitable for people with good performance status. This also applies to paclitaxel-bound proteins (nab-paclitaxel), licensed by the FDA in 2013 for use with gemcitabine in pancreatic cancer. By the end of 2013, both FOLFIRINOX and nab-paclitaxel with gemcitabine are considered a good choice for those who can tolerate side effects, and gemcitabine remains an effective option for those who do not. A head-to-head test between two new options is awaited, and trials that investigate other variations continue. However, changes in recent years only increase the survival time of several months. Clinical trials are often performed for new adjuvant therapy.
Radiotherapy
The role of radiotherapy as an adjuvant after a potentially curative surgery has been controversial since the 1980s. The European Society for Medical Oncology recommends that adjuvant radiotherapy should only be used for people enrolled in clinical trials. However, there is an ongoing trend for doctors in the US to be better equipped to use adjuvant radiotherapy than in Europe. Many clinical trials have tested various combinations of treatments since the 1980s, but failed to resolve the issue conclusively.
Radiotherapy may form part of the treatment to try to shrink the tumor to an operable state, but its use in irreversible tumors remains controversial as there are conflicting results from clinical trials. Initial results from one experiment, presented in 2013, "greatly reduced the enthusiasm" for its use in advanced stage tumors.
PanNet
Treatments of Pannets, including the less common malignant type, may include a number of approaches. Some small tumors less than 1 cm. which are accidentally identified, for example on a CT scan performed for another purpose, can be followed by a vigilant wait. This depends on the risk of the assessed surgery that is affected by the location of the tumor and the presence of other medical problems. Tumors in the pancreas alone (localized tumors), or with limited metastases, for example to the liver, may be removed surgically. The type of surgery depends on the location of the tumor, and the extent of the spread to the lymph nodes.
For localized tumors, surgical procedures may be much wider than the type of surgery used to treat pancreatic adenocarcinoma described above, but other surgical procedures are similar to exocrine tumors. The range of possible outcomes varies greatly; some types have very high survival rates after surgery while others have a poor view. Because all of these groups are rare, the guidelines emphasize that treatment should be done at a specialized center. The use of liver transplantation may be considered in some cases of liver metastasis.
For a functioning tumor, an analog somatostatin drug class, such as octreotide, can reduce excessive hormone production. Lanreotide can slow tumor growth. If the tumor does not receive surgical removal and cause symptoms, targeted therapy with everolimus or sunitinib may reduce symptoms and slow the progression of the disease. Standard cytotoxic chemotherapy is generally not very effective for PanNet, but can be used when other drug treatments fail to prevent developing disease, or on poorly differentiated PanNET cancers.
Radiation therapy is sometimes used if there is pain due to anatomical extension, such as metastasis to bone. Some PanNets absorb certain peptides or hormones, and the PanNet can respond to nuclear drug therapy with peptides or radio-labeled hormones such as iobenguane (iodine-131-MIBG). Radiofrequency ablation (RFA), cryoablation, and hepatic artery embolization can also be used.
Palliative care
Palliative care is a medical treatment that focuses on the treatment of symptoms from serious illnesses, such as cancer, and improves quality of life. Because pancreatic adenocarcinoma is usually diagnosed after progressing into an advanced stage, palliative care as a symptom treatment is often the only possible treatment.
Palliative care focuses not on treating underlying cancers, but on treating symptoms such as pain or nausea, and can aid in decision making, including when or if hospital treatment will be beneficial. Pain can be managed with drugs such as opioids or through procedural intervention, by the nerve block of the celiac plexus (CPB). It alters or, depending on the technique used, destroys the nerves that transmit pain from the stomach. CPB is a safe and effective way to reduce 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 intestinal tumors or bile ducts. For the latter, which occurs in more than half of cases, small metal tubes called stents can be inserted by the endoscope to guard the channel. Palliative care may also help treat depression that often comes with a diagnosis of pancreatic cancer.
Surgery and an inoperable tumor often lead to impaired digestive system due to lack of exocrine pancreatic products (exocrine insufficiency). It can be treated by taking pancreatin containing the pancreatic enzymes produced, and best consumed 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 gastric draining by nasogastric aspiration and drugs called proton pump inhibitors or H2 antagonists, both of which reduce the production of stomach acid. Drugs such as metoclopramide can also be used to clean the bowels.
Results
Pancreatic adenocarcinoma and other less common exocrine cancers have a very poor prognosis, as they are usually diagnosed in the late stages when the cancer has advanced locally or has spread to other parts of the body. The results are much better for PanNet: many are benign and incomplete without clinical symptoms, and even surgically remedied cases have a mean survival rate of five years at 16%, although the views vary greatly according to the type.
For locally advanced pancreatic and local metastatic pancreatic adenocarcinomas, which together represent over 80% of cases, many new trials comparing chemotherapy regimens have shown an increase in survival time, but not more than one year. Overall five-year survival for pancreatic cancer in the US has increased from 2% in cases diagnosed in 1975-77, and 4% in 1987-89 diagnoses, to 6% in 2003-09. In less than 20% of pancreatic adenocarcinoma cases with a diagnosis of local and small cancer growth (less than 2 cm in Stage T1), about 20% of Americans survive for up to five years.
About 1500 genes are associated with outcomes in pancreatic adenocarcinoma. These include poor genes, where high expression is associated with poor outcomes, such as C-Met and MUC-1, and favorable genes where high expression is associated with better survival, such as the PELP1 transcription factor.
Distribution
In 2012, pancreatic cancer produces 330,000 deaths globally, up from 310,000 in 2010 and 200,000 in 1990. By 2014, an estimated 46,000 people in the United States are estimated to be diagnosed with pancreatic cancer and 40,000 people die from it. Despite only accounting for 2.5% of new cases, pancreatic cancer accounts for 6% of cancer deaths each year. It is the seventh highest cause of cancer deaths worldwide.
Global pancreatic cancer is the 11th most common cancer in women and the 12 most common in men. The majority of cases recorded occurred in developed countries. People from the United States have an average lifetime risk of about 1 in 67 (or 1.5%) of disease progression, slightly higher than the UK rate. The disease is more common in males than females, although this rate difference has narrowed over the last few decades, perhaps reflecting an earlier increase in women who smoke. In the United States, the risk for African-Americans is over 50% greater than for whites, but the numbers in Africa and East Asia are much lower than in North America or Europe. The United States, Central and Eastern Europe, and Argentina and Uruguay all have high levels.
Pancreatic cancer is the 10th most common cancer in the UK (about 8,800 people diagnosed with the disease in 2011), and it is the 5th most common cause of cancer death (about 8,700 people die in 2012).
PanNet
The clinically recognized incidence of PanNet is low (about 5 per million person-years) and is dominated by non-functioning species. Somewhere between 45% and 90% of PanNET is considered a non-functional type. Autopsy studies have found smaller PanNETs more frequently, suggesting that the prevalence of inert and asymptomatic tumors may be relatively high. Overall, Pannet is thought to have about 1 to 2% of all pancreatic tumors. PanNet's definition and classification has changed over time, affecting what is known about epidemiology and its clinical relevance.
History
Initial recognition of pancreatic cancer has been linked to 18th-century Italian scientist Giovanni Battista Morgagni, the father of historical modern anatomical pathology, which claims to have tracked several cases of cancer in the pancreas. Many physicians of the 18th and 19th centuries are skeptical about the existence of this disease, given the appearance of similar pancreatitis. Several case reports were published in the 1820s and 1830s, and the original histopathological diagnosis was eventually recorded by American physician Jacob Mendes Da Costa, who also doubted the reliability of Morgagni's interpretation. At the beginning of the 20th century, pancreatic head cancer has become an established diagnosis.
Regarding the recognition of PanNETs, ​​the possibility of islet cell cancer was originally proposed in 1888. The first case of hyperinsulinism due to this type of tumor was reported in 1927. The recognition of the non-insulin-secreting type of PanNET is generally thought to be derived from American surgeons, R.., M. Zollinger and E.Ã, H. Ellison, who named them for Zollinger-Ellison syndrome, after postulating the presence of pancreatic tumors that secrete gastrin in a report of two extremely severe cases. stomach ulcers published in 1955. In 2010, WHO recommended that PanNET be called a "neuroendocrine" tumor rather than an "endocrine".
The first partial pancreatekoduodenektomi was reportedly performed by Italian surgeon Alessandro Codivilla in 1898, but the patient survived only 18 days before succumbing to complications. Initial surgery is compromised in part because of the false belief that people will die if their duodenum is removed, and also, initially, if the flow of pancreatic juice stops. It is then considered, also mistaken, that the pancreatic duct can only be bound without serious side effects; actually, it will very often leak later. In 1907-08, after several unsuccessful operations by other surgeons, the experimental procedure was put on trial by a corpse by a French surgeon.
In 1912, German surgeon Walther Kausch was the first to remove most of the duodenum and pancreas together ( en bloc ). This is in Breslau, now Wroc? Aw in Poland. In 1918 it was demonstrated in operations in dogs that the total elimination of duodenum was compatible with life, but this was not reported in human operations until 1935, when American surgeon Allen Oldfather Whipple published the results of a series of three operations at Columbia Presbyterian Hospital in New York. Only one of the patients had a duodenum completely removed, but he survived for two years before dying of metastasis to the liver. The first operation was unplanned, as cancer was only found in the operating room. The success of Whipple points the way for the future, but operations have remained difficult and dangerous until the last few decades. He published several improvements to his procedures, including the first total duodenal disappearance in 1940, but he made only a total of 37 operations.
The discovery in the late 1930s that vitamin K prevented bleeding with jaundice, and the development of blood transfusion as a daily process, both improved post-operative survival, but about 25% of people never left the hospital alive until the late 1970s. In the 1970s a group of American surgeons wrote insisting that the procedure was too dangerous and had to be abandoned. Since then results in larger centers have increased considerably, and mortality from surgery is often less than 4%. In 2006 a report was published from a series of 1,000 consecutive pancreaticoduodenectomies performed by a single surgeon from Johns Hopkins Hospital between 1969 and 2003. This level of surgery continued to increase during this period, with only three of them before 1980, and the median reduced operating time from 8.8 hours in the 1970s to 5.5 hours in the 2000s, and deaths in 30 days or in hospitals was only 1%. Another series of 2,050 operations at Massachusetts General Hospital between 1941 and 2011 showed a similar improvement picture.
Small precancer neoplasms for many pancreatic cancers are being detected at a very elevated level by modern medical imaging. One type, intrumuctal mucinous neoplasm (IPMN) was first described by Japanese researchers in 1982. It was recorded in 2010 that: "For the next decade, little attention was paid to this report, however, over the next 15 years, there has been a virtual explosion in recognition of this tumor. "
Direction of research
Efforts around the world at various levels are being made to understand pancreatic cancer, but its development is slow, especially in understanding the causes of disease. There are some unanswered basic questions. The nature of the disease-induced changes is being intensely investigated, such as the role played by genes like KRAS and p53 . The key question is the time when the disease develops and develops - especially the role of diabetes, and how and when the disease spreads.
Research on early detection is ongoing. For example, the European Registry of Hereditary Pancreatitis and Family Pancreatic Cancer (EUROPAC) trial aims to determine whether regular screening is appropriate for people with a family history of the disease, or who have hereditary pancreatitis. The knowledge that the onset of new diabetes could be a sign of early disease can facilitate timely diagnosis and prevention if a workable screening strategy can be developed.
Another interesting field is to assess whether keyhole surgery (laparoscopy) is better than Whipple's procedure for treating the disease through surgery, especially in terms of recovery time. Irreversible electroporation is a relatively new ablation technique that has shown hope in downstaging and prolonging survival in people with advanced local disease. It is particularly suitable for the treatment of tumors close to the peri-pancreatic vessels without the risk of vascular trauma. The limited success of postoperative results has led to a number of trials that run in 2014 to test results using chemotherapy or radiochemotherapy prior to surgery. These were not previously found to be helpful, but are being tested again, using a combination of drugs that have emerged from many post-operative therapy trials, such as FOLFIRINOX.
Efforts are being made to develop new drugs. Some of these involve targeted therapies against the molecular mechanisms of cancer cells. Others aim to target highly resistant cancer stem cells. Still others aim to influence non-neoplastic stroma and tumor microenvironment, which are known to affect cell proliferation and metastasis. A further approach involves the use of immunotherapy, such as oncolytic virus.
See also
- Gastrointestinal cancer
- Pancreas Cancer Action Network (organization in the US)
- Pancreatic Cancer Action (organization in the UK)
- Lustgarten Foundation for Pancreatic Cancer Research (US organization)
- List of people diagnosed with pancreatic cancer
References
External links
- Pancreatic cancer in Curlie (based on DMOZ)
Source of the article : Wikipedia
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