The+Gastric+Cancer+Takashi+Sato

Takashi Sato is a 65 year old Japanese male from the city of Osaka in Japan. He recently immigrated to the United States due to a job relocation. He is five feet and seven inches tall and weighs 175 pounds, which is considered slightly overweight for his height. His diet is high in sodium and preserved foods, but is relatively healthy and balanced otherwise. Takashi is a light smoker, smoking only a few cigarettes a day. His recent medical history shows that he has had multiple surgeries about four years ago to remove a few ulcers and polyps in the lining of his stomach. Despite these stomach complications, Takashi has had no other major medical complications. The rest of Takashi’s family is relatively healthy as well, but a few immediate family members had FAP syndrome in the stomach, also known as familial adenomatous polyposis, a disease where polyps occur in the stomach.

Recently, Takashi started experiencing poor appetite, abnormal abdominal pain near the navel, blood in stool, fatigue and inflammation and swelling of the stomach that continued to worsen for several days. Takashi immediately called our office and scheduled an appointment. An endoscopy, which is an operation in which we passed an endoscope down the throat, allowing us to see a mysterious growth in the lining of Mr. Sato’s stomach. The removal and biopsy of the mysterious growth confirmed that Takashi had developed gastric cancer in the lining of his stomach. In addition to finding a malignant growth, Helicobacter Pylori was also found. H. Pylori is a spiral shaped bacterium that lives in the mucus layer that coats the inside of the human stomach. H. Pylori is known to cause inflammation in the lining of the stomach that can lead to pre-cancerous changes. Unfortunately, by the time symptoms are present, it is likely that the cancer has advanced pretty significantly. Stomach cancer is especially hard to diagnosis early as it rarely causes any symptoms until the later stages of cancer progression. By that point, the tumor has probably progressed to a fairly deadly stage. 95% of cancers in the stomach are adenocarcinomas, which are cancerous tumors that develop in mucosa cells that make up the innermost lining of the stomach. As the tumor continues to grow, it will further penetrate the five layers of the stomach: mucosa, submucosa, muscularis propia, subserosa and serosa, and eventually spread to nearby lymph nodes in the process. Once the tumor is big enough, it will then metastasize and spread to nearby tissues. It takes many years for the tumor to reach this point. In the case of Mr. Sato, most of his symptoms would have most likely been caused by this cancerous growth. The blood in his stool can be attributed to the tumor in his stomach. Inflammation is also caused by the tumor as the immune system tries to combat this seemingly foreign “invader”. Fatigue would most likely be caused by losing blood in the stool and losing nutrients to the tumor. Unfortunately, with these symptoms taking full effect, the prognosis for Mr. Sato is not very promising. At best, we could say that his adenocarcinoma is stage two which means that the tumor is growing into the muscularis propia layer. While gastric cancer has become less common in recent years due to advances in food preservation, it is still just as deadly. The overall five year survival rate of this type of cancer is 29%.
 * [[image:http://www.microscopyu.com/staticgallery/pathology/images/adenocarcinomaofstomach10x01.jpg caption="Close up of adenocarcinoma"]] ||

 There are many known risk factors for the development of gastric cancer, but it is not clearly understood how these factors cause the lining of the stomach to become an ideal place for cancerous growths. Some of the most common risk factors include obesity, tobacco use, previous stomach surgeries, age, H. Pylori infection and a high sodium diet. Some researchers speculate that the long-term presence of an inflammatory response to H. Pylori predisposes cells in the stomach lining to become cancerous. This is supported by the idea that constant inflammation and damage to the lining increases cell turnover, which in turn would increase the likelihood that these new cells could develop harmful mutations that would help cancer growth to progress. Based on Mr. Sato’s life choices and everyday routine, he is a prime candidate to develop gastric cancer. The finding of H. Pylori within the lining of his stomach and the resulting painful ulcers is especially important, as this is the most likely cause of the cancer. The additional problem of having a high sodium diet magnifies the chances of developing gastric cancer exponentially because H. pylori is more likely to produce an oncoprotein known as CagA that is necessary for cancerous growths in the highly acidic environment of the stomach. People from places like Japan that consume large amounts of preserved foods are more likely to develop gastric cancer due to the high sodium content. Smoking could have also contributed to Mr. Sato's development of stomach cancer as the carcinogens from the smoke and tobacco could have entered his stomach further creating a cancer inducing environment.
 * [[image:https://microbewiki.kenyon.edu/images/thumb/2/24/H.pylori.gif/400px-H.pylori.gif caption="H. Pylori Bacteria"]] ||

 Treatment  Mr. Sato has been diagnosed with stage two-adenocarcinoma in the lining of his stomach. This means that the tumor has yet to spread, but that one tumor has grown to the muscularis propia layer in the stomach. This prognosis is very unfortunate, but it is extremely hard to prevent or catch this type of cancer early in the process. Screening, looking for the cancer before a person has any symptoms, could have possibly detected any abnormal tissue growth in the lining of the stomach before becoming full-blown adenocarcinoma. In the case of gastric cancer, the abnormal tissue could not be seen because it is internal. In addition, there is no standard or routine screening for gastric cancer, which means that the only way one would be diagnosed is if they came to the office with symptoms. By that time, the abnormal tissue growth would be a tumor.

  Despite the lack of a standard of screening for gastric cancer, there is still an effective standard of care for patients who are diagnosed. There are five different standard methods that are used to treat gastric cancer and each one has their strengths and weaknesses depending on unique circumstances of each individual case. In some instances multiple or a combination of the five are needed to tailor to a patient’s need. The five types of treatment are surgery, chemotherapy, radiation therapy, chemo-radiation and targeted therapy.

 In most cases, surgery is the best approach for patients that have cancer that are in stage 0, II or II because the tumors are still localized and have not spread. In addition, surgery does not have the harsh side affects of nausea and fatigue that accompany chemotherapy and radiation therapy. However, chemotherapy and radiation in small doses minimizes the possibilities of side affects and ensures that any small traces of cancerous cells are dead when used after surgery. Chemotherapy and radiation would be used if a cancer has metastasized because surgery would no longer be effective. Targeted therapy would hands down be the best option as it only targets cancerous cells, but it is a relatively new field that needs a lot more testing in order to be effective.

 In the case of Mr. Sato, a combination of surgery and chemotherapy would be the best course of action for stage two adenocarcinoma. Before surgery can occur a dose of neoadjuvant chemotherapy will be given to Mr. Sato in order to reduce or weaken cancer cells before operation, making it easier to remove the tumor during surgery. Neoadjuvant chemotherapy also reduces the likelihood of cancer relapse as it can kill small deposits of cancer cells that might be missed by scans or x-rays. The best chemotherapy treatment for Mr. Sato is TPF, which is a combination of three drugs, Taxotere, Platinol and Fluorouracil. Since Mr. Sato has stage 2 adenocarcinoma, TPF is recommended in this instance because it is used to treat tumors in the stomach that have advanced in size. This drug will be given to Mr. Sato intravenously, allowing for the fastest absorption of all chemotherapy methods, using an angiocatheter, which is inserted into a vein. TPF works because the three drugs that make it up aremetabolites that stop cancer cells working properly. They stop the cells making and repairing the DNA, which prevents cancer cells from growing and multiplying. After a couple weeks of chemotherapy, Mr. Sato will be ready for surgery.

 Once chemotherapy treatment is complete, subtotal gastrectomy can commence. Subtotal gastrectomy is the removal of part of the stomach that contains the tumor, nearby lymph nodes and parts of tissues near the tumor. It is imperative to remove not just the actual tumor itself but also the cancerous cells surrounding the tumor. If any cancerous cells are left behind, a relapse can occur. However, a secondary dose of chemotherapy will hopefully eliminate anything that was missed. Gastrectomy is a really effective method of treating early stage cancer as it has a 90% five-year survival rate. Since Mr. Sato’s cancer is not advanced, we are optimistic for his recovery.

<span style="font-family: Arial,Helvetica,sans-serif;"> <span style="font-family: Arial,Helvetica,sans-serif;"> After successful completion of the surgery, Mr. Sato has to stay in the hospital for a couple of weeks because he will not be able to eat solid foods for a while. As a result, he will receive nutrition through a vein for the time being until he is able to eat and drink again. After having time to recovery, Mr. Sato will go through another round of chemotherapy to ensure that all the cancer cells are eliminated. In addition to the chemotherapy and surgery treatments, Mr. Sato needs to change his diet in order to prevent any chance of relapse. A healthier diet that includes more fruits and vegetables will make Mr. Sato healthier in general. In turn, a healthier diet will also help prevent cancer. Also, additional screenings will need to be taken fairly often to also diagnose any relapses.

<span style="font-family: Arial,Helvetica,sans-serif;"> <span style="font-family: Arial,Helvetica,sans-serif;"> However, if this line of treatment is unsuccessful, there are many clinical trials that are out there that could help Mr. Sato overcome his disease. One clinical trial that could prove very effective is Vaccine Therapy with cancer-testis antigen, NY-ESO-1. This treatment involves the use of vaccines made from a person’s white blood cells mixed with tumor proteins that may help the body build an effective immune response to kill tumor cells that express the antigen, NY-ESO-1. This mixing of cells and proteins would help to illicit an immune response by exposing a particular antigen of tumor cells, prepping the body for a more full scale invasion like cancer. Gastric cancer expresses this antigen so Mr. Sato would be eligible to participate in this clinical trial. If all else fails this would be a good place to start looking for alternative therapies.

<span style="font-family: Arial,Helvetica,sans-serif;"> Molecular Basis <span style="font-family: Arial,Helvetica,sans-serif;"> Mr. Sato has been diagnosed with Stage Two adenocarcinoma in the muscularis propia layer of the inner lining of the stomach. As a result, this tumor is bigger in size and has had an opportunity to acquire some of the hallmarks of invasive cancer. Most cases of gastric cancer do not have demonstrable inheritable component. As a result, most cases tend to arise due to accumulated mutations over the span of the life of an individual. <span style="font-family: Arial,Helvetica,sans-serif;"> In terms of its connection to cancer, H. pylori act via the inflammatory process. It has been reported that H. pylori produces substances such as ammonia, phospholipases, and cytotoxins, which are released into the gastric lumen causing epithelial damage. This damage leads to a persistent state of proliferation and regeneration. This leads to a persistent state of proliferation and regeneration, increasing cell turnover and consequently more chances for mutations. As a result, the emerging characteristic of inflammation plays the most pivotal role in gastric cancer involving H. pylori. In the case of Mr. Sato and the majority of other patients who have had H. pylori infections, the up regulation of the IL1B gene almost always occurs. The IL1B gene is a cytokine that plays an important role in the inflammation immune response. The cytokine, caspase 1, produced by this gene plays an important mediatory role in inflammation response, and is involved in a variety of other cellular processes such as proliferation, differentiation and apoptosis. In the presence of H. pylori, IL1B is up regulated in response to the infection causing various inflammatory responses in the area. As a result, the IL1B gene is indirectly helping to create a microenvironment that is perfect for cancerous cells mainly through inflammation responses. With inflammation present, various nutrients are readily available in the area for cancerous cells to develop. IL-1B stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity, which are all important factors in response to infections.

<span style="font-family: Arial,Helvetica,sans-serif;"> <span style="font-family: Arial,Helvetica,sans-serif;"> While the molecular basis of gastric cancer is important to understand, the molecular basis of treatment is just as important. Targeted therapies are the way of the future, but there are few to none that have been clinically tested and approved by the FDA to be used in treating gastric cancer. Therefore, surgery and chemotherapy are the best options for treatment. These therapies are only used to treat patients after they have developed cancer. There is no preventative measure that eliminates H. pylori from the body, and it is only treated following an infection. As a result, it is extremely hard to prevent stomach cancers for those who develop infections from the bacteria. With regard to surgery, there are various types depending on the stage and severity of the tumor. To date, there is subtotal gastrectomy, total gastrectomy, gastric bypass and stent placement. Since Mr. Sato’s tumor is localized and medium sized, subtotal gastrectomy, the partial removal of the stomach is the best option. Total gastrectomy is out of the question because the tumor is too small to warrant the removal of the entire stomach. When surgery is performed, the surgeon must be sure to remove as many of the cancer cells as possible. Chemotherapy can help with this problem if it is used before and after surgery.

<span style="font-family: Arial,Helvetica,sans-serif;"> In the case of Mr. Sato, the chemotherapy drug combination TPF that is Taxotere, Platinol and Fluorouracil will be used. Using a variety or combination of chemo drugs is proven to be more effective then using just one. Taxotere is a chemo drug that is often used for gastric cancer and various other types of cancer because it is an antimicrotubule agent that inhibits the microtubule structures within the cell. Microtubules are part of the cell's apparatus for dividing and replicating itself, and inhibition of these structures ultimately results in cell death. On the molecular level, taxotere binds to microtubules reversibly with high affinity. This binding prevents the depolymerization of microtubules. In the absence of GTP, this leads to a decrease in free tubulin, needed for microtubule formation and results in inhibition of mitosis between metaphase and anaphase, preventing further cancer cell proliferation.

<span style="font-family: Arial,Helvetica,sans-serif;"> <span style="font-family: Arial,Helvetica,sans-serif;"> Platinol is another chemo drug that is used for gastric cancer that is a member of a special class of anticancer drugs that include platinum. These platinum complexes react by binding to and causing crosslinking of DNA, which ultimately triggers apoptosis. On a molecular level, the platinum complex binds to bases of the DNA, preferably guanine via the replacement of chlorides by a water molecule. This resulting exchange results in the platinum complex binding to the DNA, which causes a kink. The cancer cell does not recognize this kink and therefore apoptosis occurs because the cancer cell cannot repair the damage.

<span style="font-family: Arial,Helvetica,sans-serif;"> The third and final drug, Fluorouracil, is classified as an antimetabolite frequently used in treatment for a variety of cancers. It mimics DNA and RNA precursors resulting in the damage by messing up replication and transcription. This damage is caused by inhibiting thymidylate synthase, which is known to synthesize the pyrimidine, thymidine. Inhibition happens when Fluorouracil replaces the thymines in DNA sequences. When this happens, DNA polymerase does not recognize the base pair and more often than not, it puts the wrong complementary base in the newly synthesized strand of DNA. The resulting mutation will stop cell growth.

<span style="font-family: Arial,Helvetica,sans-serif;">Stomach cancer, like any other cancer, can become extremely deadly if it acquires the various hallmarks of invasive cancer. However, gastric cancer is very unique in that an infection involving H. pylori is the main cause of this disease. Most cancers form as a result of an accumulation of genetic mutations, but other agents have been known to cause cancer. In fact, H. pylorus has actually been classified as a carcinogen. In the past, stomach cancer was the most prevalent and deadly form of cancer in the United States in large part due to a lack of refrigeration as this reduces the need to salt and pickle foods to preserve them. As a result, incidence rates have steadily decreased over the past half-century, but that does not mean it is gone for good. With new treatments being tested in clinical trials, there may perhaps be a day where stomach cancer may no longer be as serious a diagnosis as it is today.