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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
  • Complications As pancreatic cancer progresses, it can cause complications such as: Weight loss. A number of factors may cause weight loss in people with pancreatic cancer. The cancer itself may cause weight loss.[mayoclinic.org]
  • 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]
  • 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 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 neuroendocrine cancer Less common Better chance of recovery Tumors may produce hormones and cause early symptoms , such as: Diarrhea Indigestion Blood sugar changes Weight loss Stomach pain Jaundice (Yellowing of the skin and whites of the[netrf.org]
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]
  • […] your doctor if you experience unexplained weight loss or if you have persistent fatigue, abdominal pain, jaundice, or other signs and symptoms that bother you.[mayoclinic.org]
Fever
  • […] eyes) – it also may cause your urine to be dark yellow or orange, your poo (faeces) to be pale-coloured, and itchy skin Other possible symptoms of pancreatic cancer include: nausea and vomiting changes in bowel movements (diarrhoea or constipation) fever[nhs.uk]
  • […] 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]
  • […] other than primary pancreatic ductal adenocarcinoma or neuroendocrine tumors, 8 patients (42.1%) were symptomatic and developed the following symptoms that led to further diagnostics: abdominal pain (n 4), jaundice (n 2), diarrhea (n 1), B symptoms: fever[pancreas.imedpub.com]
  • He did not complain of jaundice, fever, epigastric and back pain, inappetency, vomiting, hematemesis, melena, hematochezia, or obstipation. He denied cigarette abuse and diabetes mellitus.[journals.lww.com]
  • 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]
  • Malnutrition : pancreatic enzyme replacement (lipase).[oncolink.org]
  • Obstruction of the pancreatic duct causes steatorrhea, exacerbating weight loss and malnutrition. Patients commonly become cachectic as the disease progresses.[aafp.org]
  • Malignant gastric outlet obstruction refers to tumor blockage of the outlet of the stomach, prohibiting the passage of food from the stomach into the small intestine, and causes severe nausea and vomiting, in addition to malnutrition.[pancreapedia.org]
  • Patients with advanced pancreatic cancers and weight loss may have general laboratory evidence of malnutrition (eg, low serum albumin or cholesterol level).[emedicine.medscape.com]
Painless Jaundice
  • Therefore, a painless jaundice that becomes worse is often the first sign of pancreatic cancer. Feeling sick (nausea) and being sick (vomiting) are also fairly common symptoms.[patient.info]
  • In some cases, painless jaundice may be a symptom of early pancreatic cancer that can be cured with surgery.[medicinenet.com]
  • A tumor that obstructs the common bile duct leads to the phenomenon known as “painless jaundice” as bile constituents accumulate in the blood, often prompting an imaging study that will reveal the underlying tumor.[pancreapedia.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]
  • Jaundice usually occurs without abdominal pain. Your doctor may recommend that a plastic or metal tube (stent) be placed inside the bile duct to hold it open.[mayoclinic.org]
  • 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]
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]
  • Other symptoms that can occur with more advanced disease are: nausea, vomiting, weight loss, itching skin, and decreased appetite.[medicinenet.com]
  • When symptoms do appear, they may include upper abdominal pain radiating to the middle or the upper back; loss of appetite; significant weight loss; jaundice; itching due to high levels of bile acids accumulating in the skin; nausea and vomiting; problems[fortherecordmag.com]
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]
  • ,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]
  • 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]
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]
  • Advanced signs and late symptoms include: Jaundice (yellowing of the skin and whites of the eyes) Light-colored stools Dark urine Pain in the upper or middle abdomen and back Weight loss Loss of appetite Feeling very tired Pancreatic neuroendocrine cancer[netrf.org]
  • When symptoms do appear, they may include upper abdominal pain radiating to the middle or the upper back; loss of appetite; significant weight loss; jaundice; itching due to high levels of bile acids accumulating in the skin; nausea and vomiting; problems[fortherecordmag.com]
  • 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]
  • The main side effects of radiation therapy include mild skin irritation, loss of appetite, nausea, diarrhea, or fatigue. These side effects usually resolve soon after treatment is complete (within 1 to 2 months).[emedicinehealth.com]
Flatulence
  • ,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]
  • Question the patient as to the presence of any nausea and vomiting (especially that worsens after eating), anorexia, flatulence, diarrhea, constipation, or unusual fatigue.[medical-dictionary.thefreedictionary.com]
  • The early symptoms of pancreatic cancer are non-specific (epigastic and diffuse abdominal pain, bloating, flatulence, general malaise, diarrhea, vomiting, constipation) and can be easily missed.[omicsonline.org]
Jaundice
  • Jaundice. Pancreatic cancer that blocks the liver's bile duct can cause jaundice. Signs include yellow skin and eyes, dark-colored urine, and pale-colored stools. Jaundice usually occurs without abdominal pain.[mayoclinic.org]
  • These initial tests can usually give a good idea if the cause of jaundice is a blockage from the head of the pancreas.[patient.info]
  • 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]
  • Jaundice, pain, and weight loss are classic symptoms of pancreatic cancer.[aafp.org]
  • 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]
Hepatomegaly
  • Late findings: abdominal mass or ascites (present in 20% of patients), hepatomegaly from liver metastases, splenomegaly from portal vein obstruction, and a palpable rectal shelf. Lab studies: often normal or nonspecific.[oncolink.org]
  • Depression Migratory thrombophlebitis (ie, Trousseau sign) and venous thrombosis: May be the first presentation Palpable gallbladder (ie, Courvoisier sign) Developing, advanced intra-abdominal disease: Presence of ascites, a palpable abdominal mass, hepatomegaly[emedicine.medscape.com]
  • Important signs include an upper abdominal mass, icterus, hepatomegaly, splenomegaly, palpable gallbladder (Courvoisier’s sign), periumbilical nodules (Sister Mary Joseph’s node), ascites, and peripheral edema.[omicsonline.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
  • One type of pancreatic neuroendocrine tumor, insulinoma , may lead to too much insulin and cause blurred vision, headache, fast heartbeat, and feeling lightheaded, tired, weak, shaky, nervous, irritable, sweaty, confused, or hungry.[netrf.org]
  • 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]
  • This can cause blurred vision, headache, and feeling lightheaded, tired, weak, shaky, nervous, irritable, sweaty, confused, or hungry. Fast heartbeat. Too much glucagon may cause: Skin rash on the face, stomach, or legs. High blood sugar.[cancer.gov]
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]
  • […] pain to the midback or lower-back region Often, unrelenting pain: Nighttime pain often a predominant complaint Onset of diabetes mellitus within the previous year Painless obstructive jaundice: Most characteristic sign of cancer of head of the pancreas Pruritus[emedicine.medscape.com]
  • In addition to jaundice, rising bilirubin levels can cause severe pruritus. As hepatic function becomes compromised, patients experience fatigue, anorexia, and bruising caused by loss of clotting factors.[aafp.org]
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]
Muscle Weakness
  • This can cause muscle weakness, aching, or cramps, numbness and tingling, frequent urination, fast heartbeat, and feeling confused or thirsty. Cramps or pain in the abdomen. Weight loss for no known reason.[cancer.gov]
Mid Back Pain
  • Other possible symptoms are; abdominal pain which can get worse after meal time weight loss jaundice, which means the skin and whites of the eyes look yellow (occurs when the bile duct becomes obstructed) mid-back pain as you change position nausea and[craigscause.ca]
Dark Urine
  • Advanced signs and late symptoms include: Jaundice (yellowing of the skin and whites of the eyes) Light-colored stools Dark urine Pain in the upper or middle abdomen and back Weight loss Loss of appetite Feeling very tired Pancreatic neuroendocrine cancer[netrf.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]
  • Dark urine - caused by the jaundiced blood being filtered by the kidneys. Pale stools (faeces) - as the faeces contain no bile which causes their normal brown colour. Generalised itch - caused by the bile in the bloodstream.[patient.info]
  • Symptoms Patients (%) Weight loss 92 Weight loss 100 Jaundice 82 Pain 87 Pain 72 Nausea 43 Anorexia 64 Weakness 42 Dark urine 63 Vomiting 37 Light stool 62 Anorexia 33 Nausea 45 Constipation 27 Vomiting 37 Food intolerance 7 Weakness 35 Jaundice 7 View[aafp.org]
Confusion
  • One type of pancreatic neuroendocrine tumor, insulinoma , may lead to too much insulin and cause blurred vision, headache, fast heartbeat, and feeling lightheaded, tired, weak, shaky, nervous, irritable, sweaty, confused, or hungry.[netrf.org]
  • Pancreatic cancer should not be confused with the term pancreatitis . Pancreatitis is simply defined as inflammation of the pancreas and is mainly caused by alcohol abuse and /or gallstone formation (about 80% to 90%).[medicinenet.com]
  • This can cause muscle weakness, aching, or cramps, numbness and tingling, frequent urination, fast heartbeat, and feeling confused or thirsty. Cramps or pain in the abdomen. Weight loss for no known reason.[cancer.gov]
  • Pseudoaneurysms Pseudoaneurysms are usually not truly intrapancreatic, and they may be confused with a pancreatic cyst. These aneurysms are a complication of pancreatitis in 3.5-10% of patients.[emedicine.medscape.com]
Irritability
  • These symptoms are commonly mistaken for other conditions such as irritable bowel syndrome, colitis, asthma, or menopause. One in two neuroendocrine tumor patients is misdiagnosed.[netrf.org]
  • Side effects of this radiation therapy may include vomiting, diarrhea, fatigue, and skin irritations resembling a sunburn.[britannica.com]
  • 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]
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]
  • Symptoms may include weakness or dizziness, chills, muscle spasms, or diarrhea. Staging of Pancreatic Cancer Staging of cancer is a standardized way to classify a tumour based on its size, whether it has spread, and where it has spread.[craigscause.ca]
  • This can cause feeling thirsty, making less urine , dry skin and mouth, headaches, dizziness, or feeling tired. Low potassium level in the blood.[cancer.gov]
Asthenia
  • More specifically, one study has reported the following frequency of sign and symptoms in patients with PDAC, in descending order (13): Weakness/fatigue (asthenia)—86% Loss of appetite (anorexia)—85% Weight loss—85% Abdominal pain—79% Dark urine—59% Jaundice[pancreapedia.org]
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]

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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