The Case of the Ruthless Ruler With a Deadly Disease

Albert B. Lowenfels, MD; Patrick Maisonneuve, Eng

Disclosures

May 19, 2008

Brief Biography

Don Ferrante was born in Spain, the illegitimate son of Alfonso V of Aragon. At the age of 35, in 1458, he inherited the kingdom of Naples from his father. At that time, it had the most powerful navy in the western part of the Mediterranean. During his reign the kingdom was under steady attack not only from external powers such as the Turks, the French, the Republic of Venice, and the Papacy, but also by the local barons. He had 2 wives, 3 mistresses, and several legitimate and illegitimate children (Figure 3.)

Ferdinand I of Naples.

Ferrante was known as a politically adept but completely ruthless, evil king. He maintained power by treachery -- often imprisoning and executing his enemies. As an example of his antisocial character, on one occasion he invited many of his enemies to a banquet supposedly to celebrate a peace agreement. However, at the banquet's conclusion, many of the guests were gruesomely murdered. Some were fed to the crocodiles that guarded the castle's moat. The bodies of others were mummified so that Ferrante could display the corpses dressed in their usual costumes in the local dungeon. Even during Ferrante's time, such disrespectful treatment of one's enemies was considered unacceptable.

What is known about Ferrante's other family members?

Ferrante had numerous relatives, but little is known about their health status. No relative is known or suspected to have died from colorectal cancer. Perhaps his most well-known relative is his granddaughter Isabella of Aragon (1470-1524), also known as the Duchess of Milan. Until 2008 the Duchess of Milan was widely believed to have been the model for Leonardo Da Vinci's Mona Lisa -- possibly the world''s most famous painting. Leonardo was court painter for the Duke of Milan, and some of the details of Mona Lisa's dress suggest the sitter could have been the Duchess of Milan. In addition, there is a Raphael painting of the Duchess that resembles the Mona Lisa. More recent discoveries dispute this. The current view is that Lisa Gherardini, or Lisa Giocondo (1479-1551), wife of a wealthy Florentine businessman, Francesco del Giocondo, is the true woman whose enigmatic smile is now such a familiar image.


The death of Ferrante in 1494 is now known to have been caused by large bowel cancer. The diagnosis was delayed for several hundred years and only became apparent at the end of the 20th century when DNA analysis revealed k-ras mutations within a tumor mass compatible with colorectal cancer. This histologically confirmed case of large bowel cancer occurring during the Renaissance is unique because there is a scarcity of well-preserved tissue dating back that far that is suitable for diagnostic studies.

We are unable to make any reliable estimates of the frequency of colorectal cancer prior to the 20th century. However, today it is the third most common cancer in the United States, and on a global basis, it causes an estimated 510,000 deaths annually.

The 20th century has seen remarkable advances in our understanding of this cancer, particularly the mutations that characterize the transformation from normal colonic mucosa to adenomas and eventually to malignant disease. Just as important has been the development and increased utilization of colonoscopy as both a screening and therapeutic tool. Future advances may include new diagnostic screening tools, including computed tomography colonography and new surgical approaches such as robotic surgery and natural orifice transluminal endoscopic surgery (NOTES).

In the 15th century, when Ferrante had bowel cancer, the disease could be neither diagnosed nor treated: if he were alive today, his lesion could be treated effectively. Rather than enduring a painful death, he would likely be a survivor, able to enjoy watching or perhaps even participating in daily Italian politics.

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