GI/Liver 


Napoleon abdicating in Fontainebleau, by Paul Delaroche 

1. Napoleon's death on the Island of St. Helena has been the subject of many medical debates. Elaborate theories about arsenic poisoning and potential foul play by his British captors have been around for centuries, though few fully consider the circumstances of his death. Let's walk through the available evidence and see if we can't put this matter to rest. During the first two years of his captivity his health was relatively stable, but in January 1819 he started complaining of severe epigastric pain radiating towards his right shoulder blade. The physician's log book reported emesis, diarrhea alternating with constipation, recurrent fevers, chills, and headaches. A note from December 1820 stated "The illness of the Emperor has definitively worsened. His pulse is weak, his gums, lips and nails are colorless." In the following months he began losing weight and experiencing such severe night sweats that he had to change his clothing several times each night.

In April 1821 there was noted hematemesis, melena, and tachycardia (112 bpm). The emperor died about a month later. According to the autopsy report filed by an esteemed Italian anatomist, his stomach was filled with dark "coffee ground" like material, and there was an ulcerated lesion with raised, hardened, and irregular borders extending from the cardia to the pyloric region. There were also hardened and enlarged lymph nodes around the stomach and mediastinum. In addition to all of this, he spent his life eating a large amount salt-preserved foods and smoked meats during military campaigns. There is even speculation that an episode of GI bleeding interrupted his command duties at the battle of Waterloo, and contributed to the infamous French defeat. Seems like a classic case, what did he die of? What are two other pathologies present in this description?

 
Some say this famous pose originated from Napoleon's chronic epigastric pain.

2. Theodor Billroth was one of the greatest surgeons of the 19th century, and is best known today for developing procedures that treat refractory peptic ulcer disease. However, he was also an avid violinist, and was a dear friend to the composer Johannes Brahms. Together they were at the center of the Viennese music scene. Brahms frequently used Billroth's opinion to influence his compositions, and Brahms helped Billroth with his research on cognition and musical perception, the first of its kind. Unfortunately, Billroth died in 1894, two years before Brahms developed an illness that he potentially could have helped with (as the father of modern abdominal surgery). Less than a year before Brahms' his death an observer wrote, "He looked terribly miserable. The thin white beard, the withered face, the yellow eyes, the flabby thin body, his clothes hanging like on a hanger." His doctor also noted "considerable swelling of the liver with complete obstruction of the biliary ducts," perhaps related to his lifelong alcohol consumption or heavy smoking. Before jumping to any conclusions, it is important to note that his health was very good up until his illness began at age 73, and his decline was very rapid. Of the several possible causes of his death, which is the most likely?

 
Theodor Billroth Operating, A.G. Seligmann

3. Hollywood icon Audrey Hepburn was born in Belgium in 1929 to semi-aristocratic parents, both of whom were members of the British Union of Fascists. Luckily her father, who was a real nazi sympathizer, left the family when Audrey was six years old, and didn't have any lasting impact on her sensibilities. Though what she experienced during the war in Holland impacted her for life, and by all accounts she conducted herself quite nobly. Despite suffering from malnutrition, anemia, respiratory problems and edema, she insisted on helping with the war effort. She gave secret dance recitals to collect money for the Dutch resistance, acted as one of their underground couriers, and baked cakes out of tulip bulbs during the Dutch famine of 1944. Later in her life she became heavily involved with UNICEF, and was very dedicate to fighting child hunger around the world.

Like many who survived the war, Audrey was left with lifelong psychiatric problems, and struggled with depression and an eating disorder throughout her career. She said the one thing that helped most was gardening, which she was very passionate about. In 1993 she made an emmy-winning program called "Gardens of the World," which aimed to transmit the serenity and catharsis she found in them. However, soon after she finished filming she began having sudden, terrible abdominal pain. She checked herself into Cedars Sinai in Los Angeles and the doctors performed laparoscopic surgery. Surgeons found a tumor of the appendix that had metastasized to the small intestine, and they removed a large portion of ilium. After that she received 5-Fluorouracil and leucovorin therapy, which was largely ineffective. She died several months later at the age of 63. What she had was an extremely rare cancer of the appendix called pseudomyxoma peritonei. Based on gut physiology, can you think of what made her tumor present with sharp pain so suddenly without preceding symptoms? The answer is not appendicitis. 

 
Audrey Hepburn, 1929-1993

A clip from her excellent documentary on gardens: http://www.youtube.com/watch?v=t6ArElsvCUA

4. Dr. Frederick Treves was a British physician who had one of the most extraordinary careers in the history of medicine. He became famous for his relationship with Joseph Merrick, aka "The Elephant Man", which turned both of them into Victorian celebrities. He was also a renowned surgeon and was named honorary surgeon to the royal family. In 1902, Prince Albert of Wales (Soon to be King Edward the VII), who had waited 62 for his mother Queen Victoria to die, was finally going to assume the throne in a lavish coronation ceremony. Unfortunately, days before the event he fell ill with sharp lower right quadrant pain. Treves was called and explained that the king likely had an appendicitis, and would probably die if he did not operate. Appendectomies were not well received at the time, but Treves was adamant and finally convinced him. With the personal assistance of Lord Joseph Lister his operation was a success, the monarchy was saved, and from that point on surgery became the standard treatment for appendicitis. Dr. Treves retired having completed over 1000 appendectomies, and spent his final years traveling the world. He wound up in a Swiss nursing home, and in 1923 died from an abdominal infection. There was no autopsy, but it was noted that he suffered from peritonitis during his last few days. I searched and searched but there are no more details on this great doctor's illness. Had his pain started in the lower right it is likely he succumbed to an appendicitis of his own, but what would be the most likely diagnosis had it started on the left?

 
Dr. Frederick Treves, played by Sir Anthony Hopkins in The Elephant Man

 
A British newspaper clipping from 1902

5. There's not much history here, but I want to finish with another music clip. Pavarotti, despite his dalliances with the pop music world, was one of the most beloved singers of the 20th century. His powerful, golden voice was recognized the world over, and his death in 2007 sparked national mourning in his native Italy. A year earlier, he came to New York to have an tumor removed that appeared very suddenly and probably had something to do with his lifelong obesity. Despite complete resection and five rounds of chemotherapy, he was never able to recover. He will be missed.

  
Luciano Pavarotti, 1935-2007

 
My favorite aria, from Puccini's Tosca

 

ANSWERS (highlight to see):
1. Gastric adenocarcinoma, likely from an H. pylori infection. Cholecystitis (right shoulder blade pain), Iron deficiency anemia.
2. Pancreatic cancer (at the head of the pancreas)
3. Bowel obstruction. Ilius and intussesception often occur near the ileocecal valve and as a result of neoplasms in adults.
4. Diverticulitis
5. Pancreatic cancer

Finally, I would like to dispel a malicious rumor that our well-meaning but grossly misinformed lecturers propagated throughout the course. As brilliant as the ancient Greeks were, there is in fact no evidence that they knew about the regenerative capacities of the liver. Prometheus's liver did indeed grow back each day after being devoured by an eagle, but then, there are a whole host of other mythologies whose anatomic claims did not pan out with the coming of modern medicine. Manipulating history to reinforce our current beliefs is a slippery slope, and should not be indulged regardless of the stakes!

 
Tityus, by Titian. A lecturer used this painting to tell the story of Prometheus, unfortunately it portrays an entirely different legend concerning the god Tityus who had his liver eaten by two vultures. It's been a carnival of errors this year in terms of historical accuracy.

Hematology

 
The Latona Fountain in the gardens of Versailles

1. We will begin by revisiting a criminal investigation that took place in France in 1668. Jean-Baptiste Denis was the son of the chief hydraulics engineer to Louis the XIV, and was famous for creating an elaborate system of pumps that transported water from the Seine to the great fountains of Versailles. Rather than become an engineer himself, Jean-Baptiste decided to combine the family craft with the field of medicine. During his time as a lecturer in physics, mathematics, and medicine, he came across the work of William Harvey, and became fascinated with the possibility of blood transfusions. On June 15th 1667, he conducted the first ever animal to human transfusion using 13 ounces of lamb's blood and a series of goose quills as an I.V. line. His work made him a Parisian celebrity, but also earned him a fair number of enemies within the French Medical Academy. They were vehemently against the procedure and jealous of his position as personal physician to the king.

After a couple more "successful" trials, he performed his fourth animal-human transfusion on a madman named Antoine Mauroy, who died soon after the procedure. However, the case was wrought with suspicious behavior, especially from the man's wife who buried her husband herself to avoid the inevitable autopsy. At Denis' trial there was a witness who described Mauroy's death. Apparently he became very pale and started having seizures and may have shown evidence of GI irritation and discoloration of his nails (leukonychia striata). There was no jaundice, splenomegaly, hematuria, or fever. The judge was smart enough to know that these were the signs of overdose from a type of syphilis treatment common in those days. Denis was set free, and the wife was convicted of murder. Unfortunately the case left such a stain on Denis' reputation that he quit medicine, and the idea of transfusing blood disappeared for 150 years. Can you name the substance that killed Mauroy? What would be the cause of death from xenotransfusions?


A diagram of Denis' method

2. Most people know Pythagoras of Samos for his work on the triangle, but he was also one of the first documented polymaths. He was said to have studied medicine in Egypt, he wrote music, made extensive contributions to philosophy, and even started a kind of mystic mathematical cult called Pythagoreanism. In 529 BC he established a school near the southern Italian town of Crotone with a small group of his followers. They lived an aesthetic lifestyle, spent their free time practicing music and math, and ate an exclusively plant-based diet (interestingly, before the 1800s vegetarianism was known as The Pythagorean Diet). There was however a very strict rule against eating beans, which was likely the result of Pythagoras witnessing episodes of severe hemolytic anemia among some of his male followers. Today, the same area around Crotone is known to have the highest incidence of a certain Mediterranean genetic defect linked to this phenomenon. What is it? What is the genetic term we use to describe what happened with the Pythagoreans?


Pythagoreans celebrate sunrise by Fyodor Bronnikov


We've been here before. Pythagoras teaching music in Raphael's School of Athens

3. In 1932 two men excavated a temple in England from the 4th century AD. The temple was dedicated to the god Mars and it was written that any of his followers suffering from weakness could come drink from the temple waters and acquire some of the god's strength. Also of note was that the temple waters were frequently discolored on account of the high mineral content of the nearby soil. They even appeared red at times (hence the Mars-red connection). The two archeologists uncovered an interesting statue at the site, displaying one of the typical symptoms one might find among these weak followers. What did people come to the temple to treat? What is name of the symptom shown below?


Hand uncovered at Lydney, Gloucestershire

4. Now time for some political intrigue. In 1974 the Shah of Iran noticed a swollen lymph node in his neck, and was secretly treated by two French physicians for the next five years. He kept it a secret even from his wife until 1979, when he became severely ill at his villa in Mexico. He suddenly developed jaundice, nausea, chills, and a fever. Local doctors confused his symptoms with malaria, so an American doctor was brought in from Cornell to consult. Unfortunately he also made an incorrect diagnosis, thinking it was gallstones. But when the Shah began rapidly deteriorating his French doctors finally spoke up, and President Jimmy Carter made the very controversial decision to allow the Shah into the U.S. for treatment at Sloan-Kettering. In the hospital he received a full workup, and they discovered that he had a very unusual type of cancer characterized by an increased blood viscosity without lytic bone lesions, as well as other features typical of lymphoma. When news got out that the Shah was in the U.S. for treatment, the Ayatolla Khomeni became furious, and pro-revolutionary student groups began protesting outside of the U.S. embassy in Tehran. A quite well-known hostage crisis ensued, decades of political strife followed, and an overrated movie was made. What was the specific disease that set all of this off?


The Pahlavi Family

5. One of the greatest pianists of the 20th century is also one of the least well known. Dinu Lipatti was praised in his own lifetime by some of the most famous musicians of his age. Francis Poulenc called him "an artist of divine spirituality", and Herbert von Karajan described his playing as "no longer the sound of the piano, but music in its purest form." Though sadly, at the age of 29 he began suffering from a mysterious illness that started as a persistent fever and weight loss. After a number of incorrect diagnoses and random treatments, his doctors began administering x-ray therapy, which he said helped immensely. He also went through a trial of mustard gas injections, which caused swelling and disfigurement in his left arm. At 31 he began requiring weekly blood transfusions, and stopped chemotherapy after it destroyed one of his lungs. He remained positive and calm throughout, saying his swollen left arm gave "such formidable sonorities in the bass," and he continued touring, captivating audiences with "a different kind of expression." Based on his age and treatment, which disease was he suffering from?

 
Dinu Lipatti, Romanian classical pianist and composer (1917-1950)

In the midst of his final decline, and against the advice of his doctors, Lipatti decided to give one last recital in the French city of Besançon. Barely able to walk onstage, he gave a performance that has entered into legend, displaying an artistry that epitomized his musical purity. Towards the end of the concert, he found himself too weak to finish a series of Chopin waltzes, and ended with a simple Bach Chorale instead. The audience knew this was a final prayer from a man at the end of his life, and were moved to tears by the performance. Lipatti died ten weeks later at his home in Geneva, at the age of 33.

Listen to Dinu Lipatti's performance of J.S. Bach's Chorale, Jesu Joy of Man's Desiring:

ANSWERS (highlight to see):
1. Arsenic, autoimmune hemolytic anemia. Rumor has it members of the Paris Faculty of Medicine supplied the wife with arsenic in an attempt to frame Denis.
2. Glucose-6-phosphate dehydrogenase deficiency (G6PD), founder effect
3. Iron deficiency anemia, koilonychia. Mythology states that Iron was a gift from Mars to mankind.
4. Waldenstrom's macroglobulinemia
5. Hodgkin's Lymphoma