Can you live without a stomach? Great question. People have been asking it since at least the early 1600s. Despite that being over 400 years ago, I believe it’s safe to say that total gastrectomy is a modern medical miracle. Yes, you can live without a stomach.
Over 100 years before anyone made the connection between CDH1 mutations and stomach cancer, doctors were experimenting with total gastrectomies on humans. At that time, nobody knew whether you could live without a stomach. However, because of their work and the patients’ sacrifices, modern CDH1 mutation carriers have at least one option to prevent stomach cancer.
In honor of those who got us this far, let’s take a moment to acknowledge and celebrate their work. The below is a very high-level summary. It, therefore, omits many important facts, names, and other details about the history and current state of total gastrectomy and CDH1 mutation research. Please know, though, that the community of CDH1 mutation carriers very much appreciates all contributions to the amazing work that has given us a new lease on life.
Early days of gastric surgery
In 1960, doctors in the United Kingdom published an article entitled “The History of Gastric Surgery.” The authors report that doctors began experimenting with stomach surgery in 1810. Rather than start on humans, they experimented on dogs. The authors write: “Experimental surgery on the stomach began in 1810 when Karl Theordor Merrem, a student at the University of Giessen, demonstrated that the pylorus of dogs could be removed successfully, and without any apparent effect on their wellbeing.”
Although research on stomach surgery didn’t formalize until the early 1800s, the authors describe two instances of gastric surgery that happened in the 1600s. Those surgeries were performed to remove knives from stomachs. In one instance, in 1602, a doctor (who was also a barber?!) in Prague removed a knife from the stomach of a professional knife thrower. In the words of the authors: “The first operation is believed to have been the removal of a knife from the stomach of a professional knife thrower, by a barber and surgeon of Prague named Florian Mathies (quoted by von Eiselsberg) in 1602.”
In a second instance, in 1635, someone removed a knife from the stomach of a farm hand who swallowed the knife when trying to tickle his throat to make himself vomit. I guess he didn’t realize that using his finger would’ve been safer. As the authors write: “Thirty-three years later, on July 9, 1635, a similar successful operation was performed in Konigsberg by Christopher Schwabe (quoted by Ehrhardt). He removed by gastrotomy a knife which a young farm hand, named Andrea Grunheide, had swallowed whilst tickling the back of his throat to induce vomiting.”
It’s unclear why people in the 1600s were prone to swallowing knives, but good thing they had their surgeries. The authors report that both patients survived. For the second patient, the surgery sounds intense: “This procedure was somewhat barbarous; twice the barbers and theologians strapped their victim to a board before finding and opening the stomach.” Luckily for us, modern medicine has advanced. Gastric surgeries today are performed in a much more humane manner.
Between the 1600s and 1800s, the authors report that no additional recorded gastric surgeries can be found. However, in the early 1800s, medical professionals began experimenting on dogs. The authors write: “No further recorded operation can be found until 1849 when Charles Sedillot, Professor of Surgery at the French School of Military Medicine in Strasbourg, performed a gastrostomy after three experiments on dogs, but the patient succumbed within a few hours of the operation.”
Despite the unsuccessful attempt to perform gastric surgery on a human, that did not deter future attempts. The authors write: “Thirty-three further unsuccessful attempts were made by Sedillot.”
Eventually, over 25 years later, doctors began to realize that you can live without a stomach. The authors report that the first successful gastric surgery. The write: “it was not until 1875 that Sydney Jones, an English surgeon, reported the first successful case” of gastric surgery.
Although Dr. Jones succeeded, gastric surgery had a long way to go before being a safe and predictable procedure. Indeed, experimentation continued. The authors write: “In 1876, Carl Gussenbauer and Von Winiwarter performed many successful pylorectomies on dogs, and suggested the feasibility of this procedure on the human subject.”
Moreover, they write: “At the same time in a clinic in Vienna, Czerny and Kaiser while working as assistants to Billroth, were performing similar experiments. In one instance they resected the entire stomach of a dog, which survived and flourished for five years. “
It was around this time in the late 1800s when doctors first began formalizing guidelines for gastric surgery. Indeed, the authors report: “Under the guidance of their professor they [Czerny and Kaiser] were beginning to outline the principles of gastric surgery, which were to lead the world in this field.”
In January 1881, a doctor in Vienna named Theodore Billroth performed the first-ever successful partial gastrectomy. The patient, a 44-year-old woman, had pyloric cancer. Unlike the gastric surgeries in the 1600 mentioned above, the surgeon here had thoughtfully planned and prepared for the operation. The authors write: “The first success was not one of chance; for years he and his assistants had worked carefully and methodically to this end, and a few years before while operating on a case of gastric fistula, he had remarked that it was but a short step to the day when the human stomach could be removed surgically.”
One thing that was true then that is still true today is that only surgeons who are experienced performing gastric surgery should do it. The authors report: “He knew well the dangers and the mortality which would occur when this operation was performed by surgeons untrained and unskilled.”
Therefore, to ensure that enough doctors had the right expertise to perform and advance gastric surgery, Billroth armed his people with the right education and experience. The authors write: “He taught his pupils well and sent them out into the cities of Europe to practise and further this type of surgery . . . [They] were to lead others in the modifications which Billroth knew to be essential for its ultimate success.”
Despite Billroth’s early success and plans for advancing the state of the art, the early years of gastric surgery were riddled with perils. Complications and deaths were more common than successes.
In 1897, however, a doctor in Zurich performed the first total gastrectomy. Within two months of the surgery, the patient gained 8 pounds.
In 1898, doctors in Boston performed the second-ever successful total gastrectomy. This is the first-ever successful total gastrectomy in the United States.
These successes were no coincidence and were not without failures. Many patients died or suffered severe complications. Doctors, likely left with no other options, experimented with new techniques to see what worked and what did not. Without these heroic efforts by patients and the medical community, we would not have the modern techniques and successful outcomes that we have today.
Around 1900, with successful gastrectomies becoming the norm, people began focusing on modifying the surgical techniques to improve post-gastrectomy life. The authors write: “Total gastrectomy had become the standard treatment for extensive cancer of the stomach, but the post-operative distress of many of the patients, without any great increase in the survival rate, led many surgeons to alter their opinions about this radical operation ”
Sure, it was nice that patients were surviving their gastric surgeries. However, those victories were overshadowed by the negative consequences caused by the imperfect design of the reconstructed digestive tract. Hence, people were surviving the surgery, but it’s difficult to say they were able to live without a stomach.
Today, however, total gastrectomy is generally safe and people are able to live without a stomach. Moreover, long-term complications that require medical intervention are not the norm. Generally, patients should expect to live a normal life after total gastrectomy.
For CDH1 mutation carriers, this is great news. Researchers discovered the connection between CDH1 mutations and gastric cancer over 100 years after the first-ever successful human total gastrectomy. This sequence of events, therefore, meant that at least one powerful option existed to prevent stomach cancer in CDH1 mutants. Total gastrectomy.
Connection between CDH1 and gastrectomy
In 1998, researchers in New Zealand discovered the connection between CDH1 mutations and diffuse gastric cancer. Led by Dr. Parry Guildford, the researchers were determined to understand why multiple people within the same family were developing diffuse gastric cancer. As trained geneticists, Dr. Guildford and his team knew that coincidence was not the reason. Rather, they set out to find a molecular basis for explaining widespread occurrence of disease within the same family.
They focused on large Maori families in New Zealand that had histories of stomach cancer. In one family, the individual family members each had a 70% chance of getting the disease. This is the first family for which researchers made a connection between CDH1 mutations and diffuse gastric cancer. Indeed, in 2005, the researchers reported the following: “The first family in which CDH-1 mutations were identified was a large Maori kindred, where lifetime penetrance is 70%.”
Because researchers were able to focus on disease occurrence within families, they were able to report the first-ever molecular explanation for the disease. In their words: “Here we describe the identification of the gene responsible for early-onset, histologically poorly differentiated, high grade, diffuse gastric cancer in a large kindred from New Zealand (Aotearoa).”
One family had a mutation impacting exon 15 in the gene. Another family had a mutation impacting exon 13 in the gene. Guildford and team wrote: “In one family, a frameshift mutation was identified in exon 15, and in a second family a premature stop codon interrupted exon 13.” Other mutations exist, too. For instance, I’m missing exon 3.
In their research, Guildford and his team noticed that because of these CDH1 mutations, the affected individuals were not making enough of the E-cadherin protein. That protein, among other things, is essential for cell-to-cell adhesion. Also, it serves as a tumor suppressor.
Without enough of the properly functioning E-cadherin protein, an individual is prone to developing diffuse gastric cancer. Indeed, as Guildford and his team found: “Diminished E-cadherin expression is associated with aggressive, poorly differentiated carcinomas.”
Accordingly, they reported that testing for low levels of E-cadherin protein can indicate whether a patient is susceptible to developing the disease. They write: “Underexpression of E-cadherin is a prognostic marker of poor clinical outcome in many tumour types, and restored expression of E-cadherin in tumour models can suppress the invasiveness of epithelial tumour cells.”
By making a connection between the CDH1 mutations and family histories of diffuse gastric cancer, Guilford and his team confidently concluded that they discovered a molecular explanation for why these families were developing diffuse gastric cancer. They write: “These results describe, to our knowledge for the first time, a molecular basis for familial gastric cancer, and confirm the important role of E-cadherin mutations in cancer.”
Soon after making the connection, it appears patients were having their stomachs removed to prevent the disease. Between 1999 and 2003, Guildford and his team enrolled 33 CDH1 mutation carriers in a study where they examined the feasibility of endoscopy techniques for potentially identifying the disease in its early stages. As part of the study, at least some patients had total gastrectomies: “Total gastrectomies from patients with carcinoma were macroscopically normal but pathological mapping showed multiple microscopic foci of early signet ring cell carcinoma.”
Moreover, in 2003, at least one other group of researchers reported that total gastrectomy is recommended for CDH1 mutation carriers. They wrote: “In HDGC families the recommendation for prophylactic total gastrectomy is restricted to carriers of an inactivating CDH1 mutation.”
Therefore, because researchers in the 1800s and 1900s had developed techniques for performing total gastrectomies, CDH1 mutation researchers could recommend that mutation carriers have their stomachs removed to prevent diffuse gastric cancer. As explained elsewhere, surveillance of the stomach for disease is not a reliable option. Hence, total gastrectomy as an option for the long-term health and survival of CDH1 mutation carriers is critical. Yes, you can live without a stomach.
Want to learn more about how your digestive system works? Watch this video below.