Gallbladder carcinoma

When tissues are inflamed and irritated, they usually regenerate by cell division and laying down new protein. Tissues are mostly cells and protein after all.

Now each time a cell divides, there’s a chance that something will go wrong - a mistake will happen, and a normal gene will mutate.

If this happens with genes involved in cell replication itself, then you might have a cell that continues to divide out of control.

This is why tissues that are constantly subject to irritation and inflammation (especially tissues that are not used to it and typically don’t have as much cell division happening) are more likely to develop tumors, and the gallbladder’s no exception.

About three-quarters of patients that develop gallbladder cancer have cholesterol gallstones, and having gallstones in general is thought to increase the risk of gallbladder cancer significantly.

Why is that though? Well gallstones are known to induce inflammation of the glandular tissue along the gallbladder walls, also known as cholecystitis.

Over time, this constant state of inflammation and cell turnover increases the risk of a genetic mistakes and mutations, potentially leading to a carcinogenesis, or cancer formation.

If these cells do become carcinogenic, they proliferate and start forming a mass of these defective tumor cells in the glandular tissue of the gallbladder, which is why we can call it gallbladder adeno-carcinoma, or cancer of the glandular tissue.

With chronic inflammation of the gallbladder, the risk for carcinogenesis increases more and more over time, and that chronic inflammation of the gallbladder leads to calcification and fibrosis, a condition known as porcelain gallbladder.

Porcelain gallbladder’s actually such a high risk factor for gallbladder cancer that patients are immediately referred for cholecystectomy and removal of the gallbladder, as the risk for progressing to gallbladder cancer is as high as 50% at that point.

Although chronic inflammation is one of the biggest links to gallbladder cancer, it’s not the only link, chronic infection, particularly associated with salmonella and helicobacter, seems to raise the risk of developing gallbladder cancer.

Hereditary syndromes like Gardner syndrome and neurofibromatosis have also been associated with increased likelihood of developing gallbladder cancer.

Another interesting one is a congenital abnormality called abnormal pancreaticobiliary duct junction, where this part that comes right after the pancreatic duct and common bile duct comes together is too long.

It’s thought that in this condition, pancreatic juice, which is secreted to help digestion, just like bile, is refluxed into the bile ducts since there’s a higher hydrostatic pressure that tends to push it up the bile ducts.

Pancreatic juices getting into the bile ducts starts to change the composition of the bile, possibly through reactions with pancreatic enzymes in the pancreatic juice, but also possibly the from pancreatic juices themselves being corrosive to the lining of the gall bladder.

This is thought to lead to a chronic state of inflammation in the bile ducts, therefore making these patients more likely to develop a gallbladder cancer.

This condition is most prevalent in asian populations, particularly japanese. Since this process of chronic inflammation and progression of calcification or damage is pretty slow and occurs over years and years, gallbladder cancer isn’t usually caught until it’s progressed to later stages and is often caught incidentally, the most common case being elderly women presenting with apparent cholecystitis, often where the tumor has metastasized and invaded the neighboring liver tissue or porta hepatis, which yields a very poor survival rate.

Surgical removal of the gallbladder is typically the go-to treatment, possibly with radiation therapy but since this condition is so rare the effectiveness of radiation therapy is relatively unclear.