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Malignant Neoplasm of Pancreas

Pancreas Cancers

The malignant neoplasm of the pancreas is an aggressive type of cancer with a minimal survival rate, due to the particular biological characteristics of the tumor and the lack of symptoms prior to the advanced stage of disease [1].

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Presentation

Malignant neoplasms of the pancreas typically arise in an insidious manner, with the initial cancerous stages causing minimal or no symptoms; this indubitably explains the poor prognosis of this type of cancer, as patients seek medical advice usually when the malignancy has reached an already advanced stage.

Pancreatic cancer leads to multiple symptoms, the most characteristic of which being abdominal pain that radiates to the back, jaundice, and weight loss. The latter can occur due to the abnormal secretion of pancreatic digestive enzymes in the gastroenteric tract, poor appetite, and cachexia. Other symptoms that complete the clinical presentation may include superficial or deep venous thrombosis and gastric-outlet obstruction accompanied by vomiting. Approximately 1/4th of the patients that are initially diagnosed with pancreatic malignancy simultaneously suffer from diabetes mellitus as well and almost half of the patient's exhibit glucose tolerance abnormalities [22] [23].

Weight Loss
  • Symptoms can include tummy pain, weight loss, and feeling and being sick (nausea and vomiting). Solid pseudopapillary neoplasm Solid pseudopapillary neoplasms grow mostly in the body and tail of the pancreas.[pancreaticcancer.org.uk]
  • They include yellowing of the skin and eyes, pain in the abdomen and back, weight loss and fatigue. Also, because the pancreas is hidden behind other organs, health care providers cannot see or feel the tumors during routine exams.[icd9data.com]
  • The clinical presentation often is similar to pancreatic adenocarcinoma, with vague abdominal pain and weight loss. Identification of a large mass often involving the head and body of the pancreas should raise suspicion.[bcm.edu]
  • Pancreatic cancer leads to multiple symptoms, the most characteristic of which being abdominal pain that radiates to the back, jaundice, and weight loss.[symptoma.com]
Fatigue
  • They include yellowing of the skin and eyes, pain in the abdomen and back, weight loss and fatigue. Also, because the pancreas is hidden behind other organs, health care providers cannot see or feel the tumors during routine exams.[icd9data.com]
  • […] pancreas include: vague abdominal pain or discomfort a firm, but not tender, lump in the abdomen yellowing of the skin and the whites of the eyes (called jaundice ) weight loss diabetic symptoms, which include unusual thirst, frequent urination, extreme fatigue[cancer.ca]
Fever
  • […] cyst is asymptomatic The cyst is less than 3 cm The cyst has no solid component or mural nodule Pancreatic Pseudocysts Acute pancreatitis is a clinical syndrome characterized by abdominal and back pain that may be associated with nausea, vomiting, and fever[columbiasurgery.org]
  • Complications from this procedure are higher than those reported with routine EUS-FNA of a pancreatic cyst, with postprocedure pancreatitis occurring in between 2 and 10 % of patients, abdominal pain in 2 % to 20 %, fever in 2 %, and intracystic bleeding[link.springer.com]
Malnutrition
  • ., frequent bowel motions which appear oily, greasy and often float on the top of toilet bowel) weight loss (unintentional) malnutrition, muscle wasting diabetes (endocrine insufficiency) especially in patients who are not obese and do not have a family[pancyst.org]
Weight Gain
  • A history of fainting related to low blood sugar and weight gain commonly affects patients. Diagnosis Diagnosis for this disorder requires observation of insulin level as it relates to blood sugar level.[columbiasurgery.org]
Abdominal Pain
  • Pancreatic cancer leads to multiple symptoms, the most characteristic of which being abdominal pain that radiates to the back, jaundice, and weight loss.[symptoma.com]
  • Abdominal pain, weight loss, jaundice, and vomiting are some typical symptoms. Computed tomography, endoscopic ultrasonography, or magnetic resonance imaging are diagnostic techniques. Pancreatic cancer is usually fatal.[merckmanuals.com]
  • Unexplained weight loss, abdominal pain, nausea, vomiting. Back pain is another one, because the pancreas is very posterior in the body.[scientificamerican.com]
  • Symptoms The signs and symptoms of precancerous conditions of the pancreas include: vague abdominal pain or discomfort a firm, but not tender, lump in the abdomen yellowing of the skin and the whites of the eyes (called jaundice ) weight loss diabetic[cancer.ca]
  • Rarely cancerous, but can become large enough to cause abdominal pain and a feeling of fullness. Fortunately, most discovered pancreatic cysts are of this type. Mucinous Cystadoma. Typically located in the tail or body of the pancreas.[seenamagowitzfoundation.org]
Vomiting
  • Venous thrombosis open link of the superficial or deep veins, as well as vomiting, may also occur.[symptoma.com]
  • Symptoms can include tummy pain, weight loss, and feeling and being sick (nausea and vomiting). Solid pseudopapillary neoplasm Solid pseudopapillary neoplasms grow mostly in the body and tail of the pancreas.[pancreaticcancer.org.uk]
  • Abdominal pain, weight loss, jaundice, and vomiting are some typical symptoms. Computed tomography, endoscopic ultrasonography, or magnetic resonance imaging are diagnostic techniques. Pancreatic cancer is usually fatal.[merckmanuals.com]
  • ,inflammation of pancreas which is commonly associated with abdominal/back pain, loss of appetite, nausea and vomiting) pancreatic digestive enzyme deficiency (exocrine insufficiency) manifested by: bloating/indigestion flatulence (foul smelling) steatorrhea[pancyst.org]
  • The most common side effects include: vomiting nausea mouth sores fatigue increased risk of infection These are usually only temporary, and should improve once you've completed your treatment.[nhs.uk]
Nausea
  • Symptoms can include tummy pain, weight loss, and feeling and being sick (nausea and vomiting). Solid pseudopapillary neoplasm Solid pseudopapillary neoplasms grow mostly in the body and tail of the pancreas.[pancreaticcancer.org.uk]
  • ,inflammation of pancreas which is commonly associated with abdominal/back pain, loss of appetite, nausea and vomiting) pancreatic digestive enzyme deficiency (exocrine insufficiency) manifested by: bloating/indigestion flatulence (foul smelling) steatorrhea[pancyst.org]
  • The most common side effects include: vomiting nausea mouth sores fatigue increased risk of infection These are usually only temporary, and should improve once you've completed your treatment.[nhs.uk]
  • Early signs of pancreatic cancer include: pain in the upper abdomen loss of appetite nausea and vomiting weight loss changed bowel motions ? either diarrhoea or severe constipation jaundice (yellowish skin and eyes, and dark urine).[cancer.org.au]
  • Unexplained weight loss, abdominal pain, nausea, vomiting. Back pain is another one, because the pancreas is very posterior in the body.[scientificamerican.com]
Loss of Appetite
  • ,inflammation of pancreas which is commonly associated with abdominal/back pain, loss of appetite, nausea and vomiting) pancreatic digestive enzyme deficiency (exocrine insufficiency) manifested by: bloating/indigestion flatulence (foul smelling) steatorrhea[pancyst.org]
  • Early signs of pancreatic cancer include: pain in the upper abdomen loss of appetite nausea and vomiting weight loss changed bowel motions ? either diarrhoea or severe constipation jaundice (yellowish skin and eyes, and dark urine).[cancer.org.au]
  • Side effects of radiotherapy can include: fatigue skin rashes loss of appetite diarrhoea nausea or vomiting These side effects are usually only temporary, and should improve after your treatment has been completed. Read more about radiotherapy .[nhs.uk]
  • Tumors in the head of the pancreas typically also cause jaundice, pain, loss of appetite, dark urine, and light-colored stools.[en.wikipedia.org]
  • Often the first signs of pancreatic cancer are long-standing pain that radiates from the upper abdomen through to the back, weight loss, decreased appetite, jaundice (a yellow tinge to the skin and the whites of the eyes), dark urine and pale clay-coloured[myvmc.com]
Clay-Colored Stool
  • ., diabetes pills) to insulin jaundice manifested by: yellow eyes clay-colored stools tea colored urine pruritis (itchy skin) ** Importantly, these signs and symptoms may also develop in patients with pancreatic cancer. No.[pancyst.org]
  • stools if the pancreatic and biliary ducts are obstructed.[medical-dictionary.thefreedictionary.com]
Jaundice
  • Weight loss, abdominal pain, jaundice [a yellowing of the skin due to toxic buildup in the liver]—those are the most common symptoms. They usually start after the tumor is a significant size.[scientificamerican.com]
  • Pancreatic cancer leads to multiple symptoms, the most characteristic of which being abdominal pain that radiates to the back, jaundice, and weight loss.[symptoma.com]
  • The jaundice is accompanied by itchiness all over the body resulting from the deposit of bile salt crystals under the skin.[merckmanuals.com]
  • The recovery time is much quicker, and people find that their jaundice improves significantly.[nhs.uk]
  • There are also a variety of effective techniques available to treat bile duct obstruction which may produce jaundice and stomach obstruction caused by growth of the tumor. Both surgical and non-surgical techniques may be effective.[pancreatic.org]
Gallbladder Enlargement
  • Dullness on percussion may indicate the presence of ascites or gallbladder enlargement. Psychosocial Assess for the presence of irritability, depression, and personality changes.[medical-dictionary.thefreedictionary.com]
Blurred Vision
  • The symptoms of low blood sugar are: a headache lightheadedness blurred vision weakness shaking irritability hunger Symptoms of a Glucagonoma The symptoms of a glucagonoma include: a rash on the stomach, legs, or face diarrhea unexplained weight loss[healthline.com]
Back Pain
  • Back pain is another one, because the pancreas is very posterior in the body. Back pain is also the most common complaint that patients go to an emergency room for, and most of the time it's just muscle pain—it's not pancreatic cancer.[scientificamerican.com]
  • pain, and jaundice (if the tumor compresses the bile duct), unexplained weight loss, and digestive problems.[icd.codes]
  • Symptoms can include tummy (abdominal) and back pain, weight loss and changes to bowel habits. Read more about the symptoms of PDAC. Rare exocrine cancers One in a hundred pancreatic cancers (1%) are rare exocrine cancers.[pancreaticcancer.org.uk]
  • ,inflammation of pancreas which is commonly associated with abdominal/back pain, loss of appetite, nausea and vomiting) pancreatic digestive enzyme deficiency (exocrine insufficiency) manifested by: bloating/indigestion flatulence (foul smelling) steatorrhea[pancyst.org]
  • Less common signs include: severe back pain onset of diabetes (10-20% of people with pancreatic cancer develop diabetes).[cancer.org.au]
Pruritus
  • […] pancreatic cancer Etymology: Gk, pan kreas L, cancer, crab a malignant neoplastic disease of the pancreas characterized by anorexia, flatulence, weakness, dramatic weight loss, epigastric or back pain, jaundice, pruritus, a palpable abdominal mass, recent[medical-dictionary.thefreedictionary.com]
Dark Urine
  • […] either diarrhoea or severe constipation jaundice (yellowish skin and eyes, and dark urine). Less common signs include: severe back pain onset of diabetes (10-20% of people with pancreatic cancer develop diabetes).[cancer.org.au]
  • Often the first signs of pancreatic cancer are long-standing pain that radiates from the upper abdomen through to the back, weight loss, decreased appetite, jaundice (a yellow tinge to the skin and the whites of the eyes), dark urine and pale clay-coloured[myvmc.com]
  • Assess for the presence of pruritus and dark urine, which is caused by a buildup of bilirubin in the skin and blood, respectively. Early tumors usually cannot be palpated, but auscultate, palpate, and percuss the abdomen.[medical-dictionary.thefreedictionary.com]
  • Tumors in the head of the pancreas typically also cause jaundice, pain, loss of appetite, dark urine, and light-colored stools.[en.wikipedia.org]
Irritability
  • Symptoms may include: Feeling tired or weak Shaking or sweating Headache Hunger Nervousness, anxiety, or feeling irritable Unclear thinking or feeling uneasy Double or blurry vision Fast or pounding heartbeat If your blood sugar level gets too low, you[medlineplus.gov]
  • Psychosocial Assess for the presence of irritability, depression, and personality changes. The sudden onset of characteristic symptoms can precipitate these emotional responses.[medical-dictionary.thefreedictionary.com]
  • The symptoms of low blood sugar are: a headache lightheadedness blurred vision weakness shaking irritability hunger Symptoms of a Glucagonoma The symptoms of a glucagonoma include: a rash on the stomach, legs, or face diarrhea unexplained weight loss[healthline.com]
Seizure
  • Feeling tired or weak Shaking or sweating Headache Hunger Nervousness, anxiety, or feeling irritable Unclear thinking or feeling uneasy Double or blurry vision Fast or pounding heartbeat If your blood sugar level gets too low, you may faint, have a seizure[medlineplus.gov]
Personality Change
  • Psychosocial Assess for the presence of irritability, depression, and personality changes. The sudden onset of characteristic symptoms can precipitate these emotional responses.[medical-dictionary.thefreedictionary.com]
Dizziness
  • Symptoms Symptoms include dizziness, fatigue, weakness, uncontrolled shaking, hunger, and at times psychiatric disturbances. A history of fainting related to low blood sugar and weight gain commonly affects patients.[columbiasurgery.org]

Workup

A thorough diagnostic approach plays a pivotal role in the successful diagnosis of pancreatic cancer and also affects the type of treatment the patient will be a candidate for. Malignant neoplasms of the pancreas do not present with characteristic or pathognomonic laboratory findings and imaging modalities are those which can definitively establish a firm diagnosis.

Pancreatic tumors can be divided into two basic categories, depending on their cytological and morphological traits: cystic and solid lesions. Their morphology can be studied with the following modalities:

  • Computed tomography (CT)
  • Magnetic resonance imaging (MRI)
  • Endoscopic ultrasonography (EUS)
  • Endoscopic retrograde cholangiopancreatography (ERCP)
  • Transcutaneous ultrasonography (TUS)
  • Positron emission tomography (PET)

The lesions that are revealed through the aforementioned procedures can be biopsied; the necessity for a biopsy, however, has not yet been established and not all institutions perform it before the actual surgical procedure [24]. With regard to the distinct microscopic feature of each type of tumor, the following data exists:

  • Pancreatic ductal adenocarcinoma (PDAC): appears as a yellowish lesion, accompanied by atrophy of the tissue upstream from them and a pancreatic duct with a potentially larger diameter than usual. A rich desmoplastic layer engulfs the lesion, which comprises irregularly arranged ductal and glandular components.
  • Pancreatic neuroendocrine tumor (PanNET): a red or white lesion with a clear border, whose cells exhibit a nested developmental pattern.
  • Solid-pseudopapillary neoplasm (SPN): a lesion that gradually obtains mixed solid and cystic characteristics, with scattered hemorrhagic regions.
  • Acinar cell carcinoma (ACC): lesion characterized by its eosinophilic cytoplasm and prominent nucleoli.
  • Pancreatoblastoma: squamoid nests that, under some circumstances, can be keratinized.

The measurement of CA 19-9 levels is carried out not for purely diagnostic causes, but because its value can be used in order to pinpoint whether a malignant pancreatic tumor can be excised.

Treatment

Management for patients with malignant neoplasms of the pancreas requires the cooperation of physicians from multiple disciplines, including surgeons, oncologists, gastroenterologists, etc [25]. This is attributed to the complexity of therapeutical demands, as patients are typically diagnosed at a progressed disease stage and the response is greatly individualized.

Most occurrences of pancreatic cancer indeed require surgical intervention: the surgical procedures that can be performed includes pancreatectomy or a pancreatoduodenectomy. Surgical treatment is individualized and depends on the size of the tumor, grade of dysplasia and the existence of metastases or lack thereof:

  • Central pancreatectomy: It is used in cases where the tumor is classified as low-grade, small lesions that are centrally located. Possible complications include exo- or endocrine impairment.
  • Pancreatoduodenectomy (the Whipple procedure): involves the excision of the duodenal curve alongside the head of the pancreas, gallbladder, and common bile duct. It is opted for when the malignancy affects the head and/or neck of the pancreas and is the type of surgery most frequently performed.
  • Distal or subtotal pancreatectomy: it is carried out when the tumor is located in the tail or body.
  • Multivisceral resection: this procedure can be performed when a patient is affected by locally advanced cancer (LAPC).

Concerning the pharmacological approach to pancreatic cancer, chemotherapy can also contribute to the complete therapeutic scheme. Adjuvant treatment is reserved for patients whose operation has the aim of curing them of the malignancy [26]. Lastly, radiotherapy and neoadjuvant chemotherapy could possibly play a role in the treatment of pancreatic cancer, but their significance and efficacy have not yet been officially established.

Prognosis

Malignant neoplasms of the pancreas are exhibit a high fatality rate, mostly amongst the Scandinavian and Japanese population [20]. The disease develops insidiously and the absence of symptoms until a very progressed stage accounts for its poor prognostics, which encompass a 28% survival rate for the first year and a mere 7% survival rate for the first 5 years following the initial diagnosis [21]. Prognosis is markedly better when patients are diagnosed with precursor lesions, such as intraductal papillary mucinous neoplasms (IPMN) and mucinous cystadenocarcinomas since these type of lesions do not yet constitute a malignant pancreatic neoplasm.

Etiology

No definite causes for pancreatic cancer have been established up to this day. However, various associations and risk factors have been determined, including the following:

Except for the risk factors, a certain genetic inclination towards the disease has long ago been hypothesized. Even though no gene has been found to definitively account for malignant neoplasms of the pancreas, the involvement of genes such as BRCA2 and PALB2 is undebatable. Interestingly, up to 10% of the patients affected by pancreatic cancer have a family history of the malignancy, which implies a genetic predisposition towards it.

Epidemiology

According to epidemiologic studies in the USA, the newly diagnosed cases in 2010 were approximately 43,000, something which renders malignant neoplasms of the pancreas a relatively common type of malignancy [6]. The condition evinces a slight predilection for individuals of African descent and is followed by a high rate of fatality, as a staggering majority that amounts to 80% of the patients have already reached the stage of metastasis at the time of the initial diagnosis [7]. Data from Japan report an equally high fatality, as the malignancy is one of the predominant causes of cancer-related death in the country [8]. Malignant neoplasms of the pancreas seem to affect male patients slightly more often that female ones and the prognosis are equally poor, irrespective of the geographical region [9] [10].

Sex distribution
Age distribution

Pathophysiology

The pancreas is a unique organ that comprises two distinct parts: the endocrine gland is responsible for the production of hormones and the exocrine gland secretes digestive enzymes. The majority of all malignant neoplasms of the pancreas affect the exocrine gland and 9 out of 10 patients are diagnosed with pancreatic ductal adenocarcinoma (PDAC).

PDAC is the most invasive type of pancreatic cancer, with a multifactorial pathogenetic mechanism. The ultimate malignancy develops on the grounds of prior precursor lesions, such as pancreatic intraepithelial neoplasias (PanIN), mucinous cystic neoplasms and intraductal papillary mucinous neoplasms. The lesion that predominates the pathophysiology of pancreatic cancer is indubitably the PanIN lesion, as most of the PDACs originate from this type of damage. The signaling pathway is progressively damaged so that, ultimately, cancer can arise, and three stages have been established, comprising PanIN1, PanIN2 and PanIN3 [11].

With regard to the genetic background of malignant neoplasms of the pancreas, the predominant tumor (PDAC) has been adequately studied. It has been shown that distinct genetic alterations take place in a gradual manner, and exert a negative effect on cellular reproduction, apoptosis and various other functions that inhibit tumorigenesis. The primary genetic mutations that underlie pancreatic cancer include:

  • Mutations in the gene Kras (codon 12): occur in a staggering majority of all PDACs and increase the rate of cellular reproduction, invasion and survival ability.
  • Inhibition of p16 tumor suppressor gene: occurs later on in the course of the disease and lead to atypical cellular structure and cytological deviations.
  • Inhibition of p53 tumor suppressor gene: it occurs in approximately 70% of all PDACs. The inhibition of this gene leads to the cell's inability to initiate the apoptotic process, perform DNA repairment and block cellular division.
  • Inhibition of SMAD4 gene: occurs in half of the PDAC cases [12].

A distinct type of malignant neoplasm of the pancreas is the pancreatic neuroendocrine tumor; almost every such tumor arises as a spontaneous occurrence; nevertheless, there are some familial syndromes that lead to its development. Such syndromes are neurofibromatosis type 1 (NF1), multiple endocrine neoplasia type 1 (MEN1), von Hippel-Lindau disease (VHL) and tuberous sclerosis (TSC) [13] [14]. In cases such as these, malignancy develops on the grounds of an underlying hyperplastic substrate [14] [15] [16].

Additional genetic alterations may also arise during pancreatic tumorigenesis in the case of a solid pseudopapillary neoplasm (SPN), such as those existing in CTNNB1 (β-catenin), which are a common feature amongst all spontaneous pancreatic neoplasias [17] [18]. Another hypothesis has pointed to the 11p gene, whose multiple potential mutations contribute to the development of malignant neoplasms of the pancreas [19].

Prevention

The etiological factors that underlie pancreatic cancer have yet to be clarified; however, given the existence of certain risk factors with whom this type of malignancy is associated, there are multiple lifestyle adjustments that could contribute to its prevention. Some of them are:

  • Exercise
  • Avoidance of smoking
  • Weight limitation
  • Dietary adaptations: certain studies have pointed out to the protective role of nuts, which are believed to be chemopreventive. Fresh fruit, vegetables and a diet low in fat are considered to be paramount for the protection of the pancreas against cancer.

Other than the aforementioned suggestions, individuals with a family history of pancreatic cancer need to be more closely monitored than individuals with no prior history. The detection of genes associated with pancreatic cancer in such patients can prove life-saving, as the malignancy can be diagnosed at an earlier stage.

Summary

Malignant neoplasms of the pancreas constitute a type of cancer that is classified under those with the poorest prognosis, with northern European countries and Japan exhibiting the highest fatality rates [1]. Pancreatic cancer tends to develop without the elicitation of symptoms that would raise suspicion towards its existence and only induces significant symptomatology at an advanced stage.

Malignant neoplasms of the pancreas are divided into two categories from a microscopical point of view, the solid and cystic tumors. Depending on their cytology, they are further divided into ductal, acinar or neuroendocrine tumors. The most common type of pancreatic tumor is the pancreatic ductal adenocarcinoma, which constitutes approximately 90% of all cases of pancreatic cancers, followed by neuroendocrine tumors, which account for an additional 5%.

A clear etiology has not been established; however, risk factors such as smoking, diabetes, and an unhealthy body weight are considered to increase the possibility of developing pancreatic cancer [1]. The usual symptoms caused by the condition include jaundice, cachexia, poor appetite, weight loss, vomiting and abdominal pain that radiates to the back. Malignant neoplasms of the pancreas are diagnosed with a radiologic depiction of the tumors and treated with a surgical intervention that is dependent on the type of tumor, extent, and location. Chemotherapy is a viable option for patients in whom cancer is deemed to be curable.

Patient Information

Pancreatic cancer is a type of malignancy followed by a poor prognosis. The reason behind this, is that the disease tends to develop insidiously over a period of time, without producing any significant symptoms. When symptoms finally appear and medical assistance is sought, the malignancy has most probably reached an advanced stage. Furthermore, it does not always exhibit a positive response to chemotherapy and surgery.

There are many different types of malignant neoplasms of the pancreas, each of which consists of different type of cells and may contain fluid or be a solid mass. Not all the types of tumors share the same prognosis; in fact, the exact consistency greatly influences both, the prognosis and therapeutic approach.

Nearly 90% of all occurrences of pancreatic cancer are pancreatic ductal adenocarcinomas (PDACs). They originate from already existing lesions, called precursor lesions, that are non-malignant. Pancreatic cancer develops when these lesions, together with various genetic mutations in cancer-related genes, turn into malignant tumors.

Malignant neoplasms of the pancreas initially appear without symptoms. When the disease has progressed, the symptoms that typically appear include jaundice, abdominal pain in the upper quadrant of the abdomen that may radiate to the back, weight loss, and cachexia. Venous thrombosis open link of the superficial or deep veins, as well as vomiting, may also occur. It can be diagnosed with imaging modalities, such as a CT or MRI scan, an ERCP and various other radiologic depiction techniques that will reveal the tumor. Some surgeons require a biopsy prior to the initiation of treatment and some others do not, as the role of a biopsy has not yet been confirmed.

Treatment depends on the location of the tumor and the histological results from the biopsy if there is one. In general, treatment is surgical and consists of the removal of a certain part of the pancreas, or the pancreas and a part of the duodenum (small bowel) and gallbladder.

References

Article

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Last updated: 2018-06-21 19:10