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2.9 Lower Digestive System - Stomach Cancer Cheat Sheet (DRAFT) by

This is a draft cheat sheet. It is a work in progress and is not finished yet.

Lower Digestive System - Stomach Cancer

The breaking down of food molecules for use by body cells is called digestion, and the organs that collec­tively perform this function comprise the digestive system.
The organs of digestion are tradit­ionally divided into two groups:
1. the gastro­int­estinal (GI) tract or alimentary canal and
2. the accessory struct­ures.

Epidem­iology and Aetiology

Gastric cancer was once the second most common cancer in the world. In most developed countries, however, rates of stomach cancer have declined dramat­ically over the past half century.
In Japan, gastric adenoc­arc­inoma is the most common cancer in both males (75 cases per 100,000 popula­tion) and females (35 cases per 100,000 popula­tion). In Australia, the incidence of gastric adenoc­arc­inoma is much less, affecting 9.2 males and 4.5 females per 100,000 popula­tion.
Decreases in gastric cancer have been attributed in part to widespread use of refrig­era­tion, which has had several beneficial effects: increased consum­ption of fresh fruits and vegeta­bles; decreased intake of salt, which had been used as a food preser­vative; and decreased contam­ination of food, by carcin­ogenic compounds arising from the decay of unrefr­ige­rated meat products.
Salt and salted foods may damage the gastric mucosa, leading to inflam­mation and an associated increase in DNA synthesis and cell prolif­era­tion. Other factors likely contri­buting to the decline in stomach cancer rates include lower rates of chronic Helico­bacter pylori infection, thanks to improved sanitation and the use of antibi­otics. The increased use of screening programmes in some countries may also have played a part in reducing the incidence of gastric cancer.
Nevert­heless, gastric cancer is still the second most common cause of cancer­-re­lated death in the world, and it remains difficult to cure in Western countries, primarily because most patients present with advanced disease. Even patients who present in the most favourable condition and who undergo curative surgical resection often die of recurrent disease.
Tremendous geographic variation exists in the incidence of this disease around the world. Rates of the disease are highest in Asia and parts of South America and lowest in North America. The highest death rates are recorded in Chile, Japan, South America, and the former Soviet Union.
There are multiple risk factors for the develo­pment of gastric adenoc­arc­inoma, including precursor condit­ions, genetic and enviro­nmental condit­ions, and age. Helico­bacter pylori infection is associated with risk of stomach cancer.
Helico­bacter pylorus is a bacterium that commonly infects the mucosa of the stomach. Infection with helico­bacter pylori can cause stomach inflam­mation and peptic ulcers. It also increases the risk of stomach cancer, but only a small number of infected people develop stomach cancer.
Other known risk factors for stomach cancer include:
Long­-term inflam­mation of the stomach: People who have conditions associated with long-term stomach inflam­mation (such as the blood disease pernicious anemia) are at increased risk of stomach cancer. Also, people who have had part of their stomach removed may have long-term stomach inflam­mation and increased risk of stomach cancer many years after their surgery.
Smok­ing: Smokers are more likely than non-sm­okers to develop stomach cancer. Heavy smokers are most at risk.
Family history: Close relatives (parents, brothers, sisters, or children) of a person with a history of stomach cancer are somewhat more likely to develop the disease themse­lves. If many close relatives have a history of stomach cancer, the risk is even greater.
Poor diet, lack of physical activity, or obesity: Studies suggest that people who eat a diet high in foods that are smoked, salted, or pickled have an increased risk for stomach cancer. While people who eat a diet high in fresh fruits and vegetables may have a lower risk of this disease.
A lack of physical activity may increase the risk of stomach cancer. People who are obese may have an increased risk of cancer developing in the upper part of the stomach. The most common symptoms of stomach cancer are loss of appetite, abdominal discom­fort, weight loss, weakness (from anemia), nausea and vomiting, and tar like stools.
Approx­imately 95% of all malignant gastric neoplasms are adenoc­arc­inomas, and in general, the term gastric cancer refers to adenoc­arc­inoma of the stomach.
Other malignant tumors are very rare and include squamous cell carcinoma, adenoa­can­thoma, carcinoid tumours, and leiomy­osa­rcoma. Although no normal lymphoid tissue is found in the gastric mucosa, the stomach is the most common site for lymphomas of the gastro­int­estinal tract. The differ­ent­iation between adenoc­arc­inoma and lymphoma can sometimes be difficult but is essential because staging, treatment, and prognosis are different for each disease.

Digestive system

Anatomy and disease process

The stomach is a hollow J shaped organ, which begins at the gastro­-es­oph­ageal (GE) junction and ends at the pylorus; it is usually divided into three sections.
The uppermost part is the cardia; the middle and largest part is the body, or fundus; and the distal portion, the pylorus, which connects to the duodenum.
Unde­rst­anding the vascular supply of the stomach allows unders­tanding of the routes of haemat­ogenous spread.
The vascular supply of the stomach is derived from the celiac artery. The left gastric artery, a branch of the celiac artery, supplies the upper right portion of the stomach. The common hepatic artery branches into the right gastric artery, which supplies the lower portion of the stomach, and the right gastro­-ep­iploic branch, which supplies the lower portion of the greater curvature.
Unde­rst­anding the lymphatic drainage can clarify the areas at risk for nodal involv­ement by cancer.
The lymphatic drainage of the stomach is complex. Lymphatic drainage follows the arterial supply. Most lympha­tic’s drain ultimately to the celiac nodal area, lymphatic drainage sites include the splenic helium, supra-­pan­creatic nodal groups, porta hepatis and gastro­-du­odenal areas.
The wall of the stomach has five layers. From the lumen out, the layers include the mucosa, the sub-mu­cosa, the muscularis layer, the sub-se­rosal layer, and the serosal layer.
The peritoneum of the greater sac covers the anterior surface of the stomach. A portion of the lesser sac drapes poster­iorly over the stomach.
The gastro­-oe­sop­hageal junction has limited or no serosal covering. The right portion of the anterior gastric surface is adjacent to the left lobe of the liver and the anterior abdominal wall.
The left portion of the stomach is adjacent to the spleen, the left adrenal gland, the superior portion of the left kidney, the ventral portion of the pancreas, and the transverse colon.
Diag­nosis
The best test to diagnose gastric cancer is gast­ros­copy. Gastro­scopy is a day procedure that involves the passage of a flexible tube down the oesophagus and into the stomach which allows the surgeon to visualise the cancer and also take biopsies to confirm the diagnosis. The procedure is done with sedation and takes approx­imately ten minutes.
Disease process
The site of stomach cancer is classified on the basis of its relati­onship to the long axis of the stomach. Approx­imately 40% of cancers develop in the lower part, 40% in the middle part, and 15% in the upper part; 10% involve more than one part of the organ. Cancer of the stomach may extend directly into the pancreas, diaphragm, transverse colon, and duodenum. The liver and lungs are common sites of distant metast­ases.
Stag­ing
The minimum staging procedures once the diagnosis of gastric cancer has been confirmed with gastro­scopy include:
1. Blood tests – indicates metastatic spread to the liver.
2. Chest x-ray - looking for metastatic spread to the lung.
3. CT scan of the abdomen and chest - to ascertain spread to the lungs and liver.
4. Endo­scopic Ultras­ound - procedure similar to a gastro­scope, and is the best test to determine the depth and local invasion of the tumour. It also allows biopsies to be taken of surrou­nding lymph nodes to determine if they are involved, which determines the treatment management plan.
5. Staging laparo­scopy - to determine presence of small cancer nodules and lymph node involv­ement within the abdominal cavity that CT scan can miss. Laparo­scopy is a minor procedure that is done when all other staging procedures are clear. It is done to prevent major surgery being performed in patients whose cancer is not curable.
Other tests that may be used to look for metastatic spread are PET scans and MRI scans.
Staging of gastric cancer is usually performed using the TNM classi­fic­ation system. In the TNM staging system, a score is given for each of the three areas of interest:
Degree of tumour invasion (T staging)
Lymph node involv­ement (N staging)
Presence of distant metastases (M staging)

TNM Staging: Gastric Cancer

Treatment Management Options

Treatment for stomach cancer may involve surgery, chemot­herapy, or radiation therapy.
Radical surgery is highly successful in the treatment management of stomach cancer if disease is limited to the mucosa, but the incidence of such early lesions at diagnosis is rare.
The majority of patients with operable stage II, IIIA, or IIIB disease have at least a 60% chance of tumour recurrence and death within 5 years of diagnosis. This group therefore might benefit from adjuvant therapy.
Surg­ery: The type of surgery for stomach cancer depends mainly on the anatomical position of the tumour. The surgeon may remove the whole stomach or only the part that has the cancer.
Partial (subtotal) Gastre­ctomy for tumours at the lower part of the stomach: The surgeon removes the lower part of the stomach containing the tumour. The surgeon attaches the remaining part of the stomach to the intestine. Nearby lymph nodes and other tissues may also be removed.
Total Gastre­ctomy for tumours at the upper part of the stomach: The surgeon removes the entire stomach, nearby lymph nodes, parts of the oesophagus and small intestine, and other tissues near the tumour. Rarely, the spleen also may be removed. The surgeon then connects the oesophagus directly to the small intestine.
The propensity for gastric carcinoma to spread by means of sub-mu­cosal lymphatics suggests that a 5cm margin of normal tissue proximally and distally may be optimal. The 5-year survival rate for a curative surgical resection ranges from 60-90% for patients with stage I, 30-50% for patients with stage II disease, and 10-25% for patients with stage III disease. Due to the high likelihood of local and systemic relapse, some physicians offer adjuvant therapy.
Chem­oth­erapy has been shown to increase survival and the time it takes the disease to progress, compared to best supportive care alone. An improved quality of life with chemot­herapy compared to best supportive care has also been demons­trated.
Several chemot­her­apeutic agents have shown activity against gastric adenoc­arc­inoma, including fluoro­uracil, mitomycin, cisplatin, doxoru­bicin and methot­rexate. A standard regime includes the combined use of fluoro­pyr­imidine and cisplatin.
Patients with gastric tumours may also be tested for their human epidermal growth factor receptor 2 (HER2) status. Those with HER2 positive tumours can be treated with trastu­zumab in addition to the standard fluoro­pyr­imi­din­e/c­isp­latin regimen.
Radi­ation Therapy
Gastric adenoc­arc­inoma is relatively resistant to radiot­her­apy, with the doses required exceeding the tolerance of surrou­nding structures including the bowel, kidney and spinal cord. As a result, the use of radiot­herapy is limited to symptom control of the palliative patient. The role of irradi­ation as adjuvant therapy in completely resected but high-risk patients is being evaluated.
Radiation therapy, usually admini­stered with concom­itant 5-fluo­rou­racil (5-FU)­-based chemot­herapy, is indicated in locally confined gastric cancer that is either not techni­cally resectable or occurs in medically inoperable patients.
Patients who undergo gastric resection and have either incomplete tumour resection or truly positive margins of resection are approp­riately managed by combin­ed-­mod­ality therapy.

Radiation Therapy Planning and Treatment

The irradi­ation field should include unresected or residual tumour or the tumour bed plus major nodal regions.
Dose-l­imiting organs and structures in the upper abdomen are numerous (stomach, small intestine, liver, kidneys, and spinal cord).
With properly shaped fields, doses of 45 to 50.4 Gy in 1.8- to 2.0-Gy fracti­ons can be delivered to stomach and small intestine with a 5% or less risk of severe toxicity.
Radi­ation therapy treatment volumes
Target volumes for stomach cancer irradi­ation based on the sites of loco-r­egional failure should include for all patients;
-the gastric tumour bed
-anastomosis and stump
-regional lympha­tics.
Major nodal chains at risk include lesser and greater curvature, celiac axis, pancreatic duodenal, splenic, suprap­anc­reatic, and porta hepatis.
Beam Arrang­eme­nts
Parall­el-­opposed antero­pos­ter­ior­-po­ste­roa­nterior (AP/PA) fields are the most practical arrang­ement for the major portion of tumour nodal irradi­ation.
In most patients a portion of both kidneys will be within the AP-PA treatment field, but at least two thirds to three quarters of one kidney should be excluded (can include entirety of both kidneys to the level of 20 Gy if necess­ary).
For patients with gastro oesoph­ageal junction or proximal to mid-ga­stric cancers, one half to two thirds of the left kidney can often be spared as a result of accurate field defini­tion, which is aided by pre- and postop­erative imaging studies and clip placement.
The pancreatic duodenal nodes can be included, if indicated, while sparing 75% to 90% of the right kidney.
However, for distal gastric lesions with narrow or positive duodenal resection margins, the duodenal circum­ference may need to be included as target volume. In such instances 50% or more of the right kidney is within the field, and two thirds to three fourths of the left kidney should be spared. Chronic renal problems are infrequent when these techniques are utilised.
Dose fracti­onation regimes
With single daily fractions, the usual dose is 45 to 52 Gy delivered in 1.8- to 2.0-Gy fractions over 5.0 to 5.5 weeks, with a field reduction after 45 Gy. Reduced boost fields to small areas of residual disease can sometimes be cautiously carried to doses of 55 to 60 Gy.
Pall­iative Radiation Therapy
Evidence evaluating the use of radiation therapy in patients with locally recurrent or metastatic carcinoma of the stomach is limited due to small patient numbers. The role of radiation therapy in patients with advanced stomach cancers is likely to be limited to palliation of sympto­ms—such as bleeding or contro­lling pain secondary to local tumour infilt­ration and biliary obstru­ction. Although minimal data is available, radiation therapy seems to be fairly effective (from anecdotal experi­ence) in contro­lling bleeding, as is true in other sites. This can often be accomp­lished at relatively low radiation doses. Pain from local tumour invasion can also be palliated, although the doses required are higher (45 Gy).

Treatment sequelae and patient ca

Toxicity is often the limiting factor in radiation therapy involving both the lower and upper digestive system.
The acute effects of radiation include mucosal denuda­tion.
Late effects consist of fibrotic changes leading to reduced mobility and ischemia.
Multi-­field and conformal radiation therapy, as well as accurate and reprod­ucible patient positi­oning techni­ques, reduce the volume of normal tissue exposed to radiation and can decrease the potential toxicity.
However, the treatment management approaches for radiation toxicity are mainly supportive care. The increased use of concurrent chemot­herapy and radiation therapy, has required enhanced awareness of potential effects and better methods to decrease toxicity, as this combin­ation of treatments is associated with a higher rate of gastro­-in­tes­tinal toxicity.
Radiation to the upper abdomen can produce anorexia and nausea, which may exacerbate the patient’s already poor nutrit­ional status.
Transient mal-ab­sor­ption may occur as a result of diffuse damage to the bowel mucosa in the irradiated field.
Symptoms such as inflam­mation, endart­eritis, and fibrosis, with possible stricture formation or ulcera­tion, may further compromise absorption function.
Common complaints during gastric irradi­ation include: Anorexia, Nausea, and Fatigue
  

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