Pancreatic Cancer

Pancreatic Cancer, Pancreatic Carcinoma, Pancreatic Neoplasms

In medical parlance, the pancreatic cancer is known as infiltrating ductal adenocarcinoma of the pancreas. This cancer is the third leading cause of cancer deaths, preceded only by lung and colon cancers. Although it is substantially less common than the other two malignancies, pancreatic carcinoma nears the top of the list of killers with one of the highest mortality rates. Worldwide, more than a quarter of a million were diagnosed with pancreatic cancer in 2019, and virtually all will die in a short period after diagnosis; the 5-year survival rate is a dismal 8%. God bless them!

Cells divide to form new cells when the body needs them. Our body destroys old cells that are no longer functioning properly. DNA mutations can cause cells to grow and divide uncontrollably. Old cells may refuse to die when their time is over. Mutations are essentially inherited, though at times also acquired due to life-style or as occupational hazards. This accumulation or mass-formation is called a tumor. Tumors can be benign or malignant. Malignant tumors cause cancer.

Types

Now, pancreatic cancer is of two types. More common is exocrine in which cancer begins in the cells lining the ducts of the pancreas. It is called pancreatic adenocarcinoma. Endocrine type is rare and less than 5% of all the cases. It starts in the hormone-producing cells and is called pancreatic neuro-endocrine cancer or islet cell tumors. Neoplasms of exocrine pancreas can be cystic or solid, and benign or the most lethal of all malignancies.

Cystic Neoplasms

The term cystic neoplasm covers diverse tumors ranging from harmless benign cysts to invasive, potentially lethal, cancers. Approximately 5% to 15% of all pancreatic cysts are neoplastic; these constitute less than 5% of all pancreatic neoplasms. Some of these are almost always benign (e.g., serous cystadenoma); others, such as mucinous cystic neoplasms, can be benign or malignant.

Serous cystadenomas

  • account for approximately 25% of all pancreatic cystic neoplasms
  • composed of glycogen-rich cuboidal cells surrounding small cysts containing clear, straw-coloured fluid
  • The tumors typically manifest in the seventh decade of life with nonspecific symptoms such as abdominal pain
  • Female-to-male ratio is 2 : 1.
  • These tumors are almost uniformly benign, and surgical resection is curative in the vast majority of patients.

Mucinous cystic neoplasms

  • Close to 95% arise in women, usually in the body or tail of the pancreas, and manifest as painless, slow-growing masses.
  • Non-invasive mucinous cystic neoplasms harbour low-grade, moderate, or severe dysplasia.
  • Up to one-third of these cysts can be associated with an invasive adenocarcinoma, another important difference from the serous tumors.
  • Distal pancreatectomy for non-invasive mucinous cysts typically is curative, even in the setting of severe dysplasia.

Intraductal Papillary Mucinous Neoplasms (IPMN)

  • More frequently found in men than in women. More often the head of the pancreas is involved.
  • As with mucinous cystic neoplasms, the epithelia of noninvasive IPMNs harbour various grades of dysplasia, and a subset of lesions is associated with invasive adenocarcinoma.
  • In particular, “colloid” carcinomas of the pancreas, which are adenocarcinomas associated with abundant extracellular mucin production, nearly always represent malignant transformation of an IPMN.
  • Up to two-thirds of IPMNs harbour oncogenic mutations of GNAS on chromosome 20q13, which encodes the alpha sub-unit of a stimulatory G-protein, Gs. Activation of this G-protein results in an intracellular cascade that promotes cell proliferation.

Pathogenesis

As with other cancers, pancreatic cancer is the consequence of inherited and acquired mutations in cancer-associated genes. In a pattern analogous to that seen in the multistep progression of colon cancer, there is a progressive accumulation of genetic changes in pancreatic epithelium as it proceeds from non-neoplastic, to noninvasive precursor lesions, to invasive carcinoma.

The four genes that are most commonly affected by somatic mutations in this neoplasm are KRAS, CDKN2A/p16, SMAD4, and TP53. The general temporal sequence of changes is not insignificant but the accumulation of multiple mutations is more important than their occurrence in a specific order.

The activation of the oncogene K-RAS with simultaneous inactivation of the tumor suppressor genes results in pancreatic cancer. The concerned tumour suppressor genes are p53, DPC4, p16, and BRCA2. Ninety percent of all cases of pancreatic cancer have p16 mutations, 75 % have p53 mutations, and 55 % have DPC4 mutations.

Pancreatic cancer is primarily a disease of senior citizens. 80% of the cases occur between 60 and 80 years of age. The habit of smoking doubles the risk. Long-standing chronic pancreatitis and diabetes mellitus also modestly increase the risk of pancreatic cancer. In fact, these two have a bidirectional link with pancreatic cancer. They cause and are caused by each-other.

MORPHOLOGY

Approximately 60% of pancreatic cancers arise in the head of the gland, 15% in the body, and 5% in the tail; in the remaining 20%, the neoplasm diffusely involves the entire organ. Carcinomas of the pancreas usually are hard, grey-white, poorly defined masses.

Two features are characteristic of pancreatic cancer:

  1. It is highly invasive (even “early” invasive pancreatic cancers invade peripancreatic tissues extensively), and
  2. It elicits an intense host reaction in the form of dense fibrosis (desmoplastic response).

Most carcinomas of the head of the pancreas obstruct the distal common bile duct as it courses through the head of the pancreas. In 50% of such cases, there is marked distention of the biliary tree, and patients typically exhibit jaundice. In contrast, carcinomas of the body and tail of the pancreas do not impinge on the biliary tract. Pancreatic cancers often extend through the retroperitoneal space, entrapping adjacent nerves (thus, accounting for the pain), and occasionally invade the spleen, adrenal glands, vertebral column, transverse colon, and stomach. Peri-pancreatic, gastric, mesenteric, and porta-hepatic lymph nodes frequently are involved, and the liver often is enlarged with metastatic deposits. Distant metastases may occur, principally to the lungs and bones.

Clinical Features

Carcinomas of the pancreas typically go unnoticed until on extension they impinge on some other structure. Pain usually is the first symptom, but by that point most often cancer has got to the advanced stage beyond cure. It is not that there aren’t any complications. Obstructive jaundice can be associated with carcinoma in the head of the pancreas, but it rarely draws the attention of either the patient or the doctor to cancer soon enough for timely intervention. Jaundice is treated, cancer goes unattended to. Weight loss, anorexia, and generalized malaise and weakness are manifestations of advanced disease. New-onset diabetes is often the first manifestation of pancreatic cancer. Sadly, the pancreatic carcinoma progresses rapidly and often the clinical course is distressingly brief to intervene effectively. Less than 20% of pancreatic cancers are resectable at the time of diagnosis.

Pancreatic Cancer, Pancreatic Carcinoma, Pancreatic Neoplasms

Symptoms

The disease is mostly diagnosed after age 60. It is seldom detected in early stages as symptoms often don’t occur until the disease is advanced. If one or more of the following symptoms are chronic or occur suddenly in combination, then it may be a signal to pancreatic cancer.

  • Pain in the upper abdomen radiating to the back
  • Weight loss
  • New-onset diabetes
  • Jaundice

Causes & Complications

The following may happen in sequence:

  • Mutations in the DNA of pancreatic cells
  • Uncontrollable growth of cells
  • Accumulation of cells
  • Formation of tumor
  • Pressure on duodenum blocking the flow of digested food from stomach into intestines
  • Pain and loss of appetite
  • Left untreated, cancer typically spreads to nearby organs and blood vessels

Prevention

Healthy diet, healthy weight, moderate exercise and no smoking are advised. If there is a family history of such cancer, one may meet specialists for early genetic diagnosis as the disease is essentially due to mutations. Treatment may include surgery, chemotherapy, radiation therapy or a combination of these.

Prognosis

The disease is still largely incurable and fatal. For all stages of pancreatic cancer combined, the one-year relative survival rate is 20%, and the five-year rate is just 7%. The low survival rates are because diagnosis in most cases is too late for surgical action. There are different stages, stage 4 being advanced where cancer has spread to other part(s) of the body. In fact, patients with the uncommon pancreatic endocrine tumour have a rather better outlook than the exocrine type of pancreatic cancer. Overall, survival depends on many factors like individual condition, type of cancer, treatment and level of fitness.

Read: Acute and Chronic Pancreatitis

To conclude, with many facets of pancreatic cancer being increasingly understood, prospects of prevention are becoming apparent. Many issues still remain to be resolved. Role of data in facilitating this cannot be over-emphasized. Unfortunately, representative data on the epidemiology of carcinoma of the pancreas in India are inadequate.

Secondly, basing a patient’s treatment on his/her molecular profile improves outcomes. It’s encouraging to see pharmaceutical companies and the FDA moving in the direction of more personalized treatments for patients based on their tumor’s biology instead of simply its location in the body.

Abstract

  • Pancreatic cancer probably arises from noninvasive precursor lesions (most commonly, PanINs), developing by progressive accumulation of mutations of oncogenes (e.g., KRAS) and tumor suppressor genes (e.g., CDKN2A/p16, TP53, and SMAD4).
  • Typically, these neoplasms are ductal adenocarcinomas that produce an intense desmoplastic response.
  • Most pancreatic cancers are diagnosed at an advanced stage, accounting for the high mortality rate.
  • Obstructive jaundice is a feature of carcinoma of the head of the pancreas; many patients also experience debilitating pain.
  • Carcinomas of the tail of the pancreas are often not detected until late in their course.

1 thought on “Pancreatic Cancer”

  1. Pingback: Acute & Chronic Pancreatitis Functions, Diseases, Overview

Leave a Comment

Your email address will not be published. Required fields are marked *